cap.3, extracte

A Review on y(Basidiomyce la

Authors

Affiliations

Key wordsl" mushroomsl" Basidiomycetesl" antimicrobialsl" grampositive bacterial" gramnegative bacteria

received July 3, 2012revised August 8, 2012accepted August 22, 2012

BibliographyDOI http://dx.doi.org/10.1055/s-0032-1315370Published online September 21,2012Planta Med 2012; 78:17071718 Georg ThiemeVerlag KG Stuttgart New York ISSN 00320943

CorrespondenceProf. Isabel C. F. R. Ferreira,PhDInstituto Politcnico de BraganaCampus de Santa Apolnia,apartado 11725301855 BraganaPortugalPhone: + 351273303219Fax: + [email protected]

1707ReviewsAntimicrobial Activittes) Extracts and IsoIntroduction!

Mushroom bioactivityFor a long time, mushrooms have been playing animportant role in several aspects of human activ-ity. Edible mushrooms, for example, are used ex-tensively in cooking and make up part of low-cal-orie diets. Mythology is extensively garnished bymushrooms and is typically associated withgnomes, fairies, and other fairytale personages.

Abstract!

Despite the huge diversity of antibacterial com-pounds, bacterial resistance to first-choice anti-biotics has been drastically increasing. Moreover,the association between multiresistant microor-ganisms and nosocomial infections highlight theproblem, and the urgent need for solutions. Natu-ral resources have been exploited in the last yearsand among them, mushrooms could be an alter-native source of new antimicrobials. In this re-view, we present an overviewof the antimicrobialproperties of mushroom extracts and highlightsome of the active compounds identified, includ-ing low- and high-molecular weight (LMW andHMW, respectively) compounds. LMW com-pounds are mainly secondary metabolites, suchas sesquiterpenes and other terpenes, steroids,anthraquinones, benzoic acid derivatives, andquinolines, but also primary metabolites such asoxalic acid. HMW compounds are mainly pep-tides and proteins. Data available from the litera-ture indicate a higher antimicrobial activity ofmushroom extracts against gram-positive bacte-ria. Among all the mushrooms, Lentinus edodes isthe most studied species and seems to have abroad antimicrobial action against both gram-postive and gram-negative bacteria. Plectasinpeptide, obtained from Pseudoplectania nigrella,is the isolated compoundwith the highest antimi-

Maria Jos Alves1,2,3,4, Isabel C. F. R. Ferreira3, Joana Dias4, V

1 CBQF-Escola Superior de Biotecnologia, Universidade Catlica2 Centro Hospitalar de Trs-os-Montes e Alto Douro-Unidade de3 CIMO-Escola Superior Agrria, Instituto Politcnico de Bragan4 Escola Superior de Sade, Instituto Politcnico de Bragana, Br

Alvof Mushroomted CompoundsThe psychedelic and consciousness expansionproperties of some species have pushed mush-rooms to become part of some religions. Eventoxic mushrooms have found a place of relevance,because of the uniqueness of their compoundsthat evolved naturally as a protection against con-sumption [1].Wild and cultivated mushrooms contain a hugediversity of biomolecules with nutritional [2]and/or medicinal properties [35]. Due to these

crobial activity against gram-positive bacteria,while 2-aminoquinoline, isolated from Leucopax-illus albissimus, presents the highest antimicrobialactivity against gram-negative bacteria.

Abbreviations!

CSAP: Cordyceps sinensis antibacterial pro-tein

CFU: colony forming unitiesERSP: erythromycin-resistant Streptococcus

pyogenesHMW: high-molecular weight compoundsIC50: concentration inhibiting 50% of the

growthIZD: internal zone diameterLMW: low-molecular weight compoundsM: myceliumMIC: minimal inhibitory concentrationMRSA: methicillin-resistant Staphylococcus

aureusMRSE: methicillin-resistant Staphylococcus

epidermidisPABA: para-aminobenzoic acidPRSP: penicillin-resistant Streptococcus

pneumoniaVREF: vancomycin-resistant Enterococcus

faecium

nia Teixeira4, Anabela Martins3, Manuela Pintado1

Portuguesa Porto, Porto, PortugalChaves, Chaves, Portugala, Campus de Santa Apolnia, Bragana, Portugalagana, Portugal

es MJ et al. A Review on Planta Med 2012; 78: 17071718

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properties, they have been recognized as functional foods, and asa source for the development of medicines and nutraceuticals.Fruiting bodies, mycelia, and spores accumulate a variety of bio-activemetabolites with immunomodulatory, cardiovascular, liverprotective, antifibrotic, anti-inflammatory, antidiabetic, antiviral,antioxidant, antitumor, and antimicrobial properties [314].The frequent use of mushrooms is based on three main assump-tions: first, they are used as part of a regular diet for their nutri-tional value (since they are rich in water, minerals, proteins, fi-bers, and carbohydrates, and are low-caloric foods due to a lowcontent in fat [2]); secondly, fruiting bodies are also appreciatedfor their delicacy (they are palatability enhancers of flavor andaroma when associated to other foods); and thirdly, mushrooms

are widely used for medicinal purposes. Their pharmacologicalaction and therapeutic interest in promoting human health havebeen known for thousands of years [5,15,16].In particular, mushrooms could be a source of natural antibiotics,which can be LMW and HMW, respectively, compounds. LMWcompounds are mainly secondary metabolites such as sesquiter-penes and other terpenes, steroids, anthraquinone and benzoicacid derivatives, and quinolines, but also primary metabolitessuch as oxalic acid (l" Fig. 1). HMW compounds mainly includepeptides and proteins.It is estimated that there are about 140000 species of mush-rooms on earth, and of these only 22000 are known and only asmall percentage (5%) has been investigated. Therefore, there is

ith

1708 Reviews

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ted.Fig. 1 Chemical structure of the low-molecular weight (LMW) compounds wAlves MJ et al. A Review on Planta Med 2012; 78: 17071718antimicrobial potential found in mushrooms.

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Bacteria and drug discoveryThe development of antibiotics has been one of the most impor-tant scientific achievements of the last seventy years. These com-pounds act in several ways, by interfering in metabolic processesor in the organism structures [17]. The mechanism of action ismostly related with interferences in the synthesis of the cell wall,modification of plasmatic membrane permeability, interferencesin chromosome replication, or in protein synthesis [18]. The cellwall is responsible for the shape and rigidity of bacterial cells, act-ing as an osmotic barrier [19]. The peptidoglycan content in thecell wall varies between 10% and 60% for gram-negative andgram-positive bacteria, respectively [20,21].Antiparietal antibiotics act in one of the phases of peptidoglycansynthesis, being classified according to that phase. Phosphomy-cin, D-cycloserine, glycopeptides (bacitracin, vancomycin, teico-planin), and beta-lactams (penicillins, cephalosporins, carbape-nemics, monobactamics) are some examples of this group [22].Otherwise, other antibiotics such as ascolistin and daptomycinact at the cell membrane level. Aminoglycosides and tetracy-clines, macrolides, oxazolidines, quinupristin and dalfopristin,clindamycin, and chloramphenicol inhibit protein synthesis byinterfering with 30 s or 50 s ribosomal subunits. Quinolones, ri-fampicin, andmetronidazol inhibit nucleic acid synthesis. Sulfon-amides and trimetoprim are antimetabolic antibiotics that inhib-it the metabolic chain of PABA, essential to cell growth [23].Despite the huge diversity of antibacterial compounds, bacterialresistance to first-choice antibiotics has been drastically increas-ing. Some examples are microorganisms such as Klebsiella spp.and Escherichia coli, which produce broad-spectrum beta-lacta-mase or present resistance to third-generation cephalosporins.Other examples include MRSA, Enterococcus spp., which is resist-ant to vancomycin [24,25], Acinetobacter spp. with an increasingresistance to carbapenems and colistin [26], and Pseudomonasspp., which is resistant to aminoglycosides, carbapenemics. and/or cephalosporins [24].Diseases that were easily healed are nowadays becoming a seri-ous problem due to emergent antibiotic resistance [27,28]. Theassociation between multiresistant microorganisms and hospitalinfections certainly highlights this problem and the urgent needfor solutions [29]. In 2010, the World Health Organization ad-vised all countries to implement control procedures for the prop-agation of drug multiresistant bacteria, highlighting the risks as-sociated to the absence of alternative therapies against those mi-croorganisms [30].Therefore, the research of new antimicrobial substances effectiveagainst pathogenic microorganisms resistant to current drugs iscrucial. New groups of organisms, such as marine, have been in-creasingly explored in the last years, and among them, mush-rooms could be an alternative source for new antimicrobials. Inthis review, we provide an overview about the antimicrobialproperties of mushroom extracts and highlight selected com-pounds. The databases searched were Medline (1980 to March2012) and Web of Science (2001 to March 2012) including scien-tific articles and conference proceedings. Search terms were:mushrooms, antimicrobial activity, and antimicrobials. Anexhaustive literature search was performed, but only mushroomextracts and isolated compounds with positive results were in-cluded.Antimicrobial Activity Against Gram-Positive Bacteria!

MethodologiesDifferent methodologies have been used to assess antimicrobialactivity of mushroom extracts and compounds, including the mi-crodilutionmethod, the disk diffusionmethod, the agar streak di-lution method based on radial diffusion, and a method with theincorporation of the extract in the culture medium and furtherdetermination of colonies. Therefore, the results for antimicrobialactivity are expressed in different unities (l" Tables 1 and 2).The microdilution method comprises microdilutions of the ex-tract in liquid medium using microplates to determine MIC orIC50 values. In the disk difusion method, the extract is incorpo-rated in disks at different concentrations, and the halo of growthinhibition is determined and represented by IZD (internal zonediameter) values. The agar streak dilutionmethod based on radialdiffusion is most widely used in extracts and implies the extractapplication in circular holes made in solid medium. The resultmight be expressed in IZD or MIC values. Regarding the fourthmethod, the extract is incorporated in the culture medium andthen CFU are determined.

Mushroom extracts with antimicrobial activityNumerous mushroom extracts have been reported as havingantimicrobial activity against gram-positive bacteria (l" Table 1).Agaricus bisporus, the most cultivated mushroom in the world,should be highlighted. Its methanolic extract revealed MIC =5 g/mL against Bacillus subtilis, even lower than the standardampicillin (MIC = 12.5 g/mL) [31], and also showed activityagainst Bacillus cereus, Micrococcus luteus, Micrococcus flavus,Staphylococcus aureus, and Staphylococcus epidermidis [15,32,33]. Other Agaricus species have also demonstrated antimicrobialactivity. Agaricus bitorquis and Agaricus essettei methanolic ex-tracts showed an inhibitory effect upon all the tested gram-posi-tive bacteria [15]. Agaricus silvicola methanolic extract also re-vealed antimicrobial properties against Bacillus cereus (MIC =5 g/mL), Bacillus subtilis (MIC = 50 g/mL), and against Staphylo-coccus aureus (MIC = 5 g/mL), lower than the standard ampicillin(MIC = 6.25 g/mL) [31]. The mycelium of Agaricus cf. nigrecentu-lus and Tyromyces duracinus (ethyl acetate extracts) showed ac-tivity only against Staphylococcus saprophyticus [34].The ethanolic extracts of Armillaria mellea mycelium showed anantibacterial effect against Sarcina lutea; however, no activitywas observed upon other gram-positive bacteria [35]. However,the ethanolic extract of their fruiting bodies showed broad-spec-trum antimicrobial activity [36].The most studied mushroom of the genus Boletus is Boletusedulis. Its methanolic mushroom showed lower antimicrobial ac-tivity than other species studied by Ozen et al. [32]. Nevertheless,Barros et al. [31] reported an MIC = 5 g/mL against Staphylococ-cus aureus, lower than ampicillin (MIC = 6.25 g/mL).Cantharellus cibarius methanolic extract demonstrated good ac-tivity against Bacillus subtilis and Staphylococcus aureus [31,32,37]. This mushroom also showed activity against Bacillus cereusin some studies [32,37], but it was not so effective in another re-port [31], which could be related to the different methodologiesused to evaluate antimicrobial activity.Clitocybe alexandri methanolic extract presented significant ac-tivity against Bacillus subtilis andMicrococcus luteus [38]. Kalyon-cu et al. [36] tested antimicrobial activity of chloroform and etha-nolic extracts from Clitocybe geotropa, the latter showing asigni-

ficant capacity against Bacillus cereus.

Alves MJ et al. A Review on Planta Med 2012; 78: 17071718

Table

1Mushroo

mextractswithan

timicrobialactivity

againstgram

-positiveba

cteria.

Microorgan

ism

Mushroom

aRe

sults

References

Actin

omyces

naeslund

iiLentinus

edod

esCFU

=0

3.30

(5.48

)10

6

MIC

=0.052

0mg/mL

[53,54

,67]

Actin

omyces

viscos

usLentinus

edod

esMIC

=0.052

0mg/mL

[54]

Bacillu

scereus

Agaricus

bisporus

,Aga

ricus

bitorquis,Ag

aricus

essettei,A

garic

ussilvicola,

Armillaria

mellea,

Boletused

ulis,C

antharellusciba

rius,Clito

cybe

alexan

dri,

Clito

cybe

geotropa

,Cortin

ariussp.,Gloeo

porusthelep

horoides,H

exag

onia

hydn

oide

s,Hyd

num

repa

ndum

,Hyp

holomafasciculare,Irp

exlacteu

s(M

),La

ctariusca

mph

orates,Lac

tariu

sdelicious

,Lac

tariu

spiperatus

,Lac

tariu

svolem

us,Lae

tiporus

sulphu

reus

,Len

tinus

edod

es,Lep

ista

nuda

,Leu

copa

xillu

sgiga

nteu

s(M),Mac

rolepiotaproc

era,

Meripilu

sgigan

teus

(M),Meripilu

sgigan

teus

,Phe

llinu

ssp.,P

leurotus

ostrea

tus(M),Pleu

rotuso

streatus

,Ram

aria

botrytis,R

amaria

flava

,Rhizo

pogo

nroseolus

,Sarco

donim

bricatus

,Spa

rassiscrispa

,Tric

holomapo

rten

tosu

m

IZD=5

21mm

MIC

=5g

/mL10

0mg/mL

[11,15

,31,32

,343

8,454

8,50

,55]

Bacillu

smeg

aterium

Lentinus

edod

esCFU

=0(totalinhibition

)[52]

Bacillu

spum

ilis

Lentinus

edod

esIZD=14

mm

[50]

Bacillu

ssu

btilis

Agaricus

bisporus

,Aga

ricus

bitorquis,Ag

aricus

essettei,A

garic

ussilvicola,

Armillaria

mellea,

Cantha

rellu

sciba

rius,Clito

cybe

alexan

dri,Clito

cybe

geo-

trop

a,Co

rtinariussp.,Gan

odermalucidu

m,H

ygroph

orus

agatho

smus

,Hyp

holomafasciculare,La

ctariusde

licious

,Lac

tariu

spiperatus

,Lae

tiporus

sul-

phureu

s,Lentinus

edod

es,Lep

ista

nuda

,Leuc

opax

illus

giga

nteu

s(M),Meripilu

sgigan

teus

(M),Nav

espo

rusfloccosa,

Paxillu

sinv

olutus

(M),Ph

ellin

usrim

osus

,Pleurotus

ostrea

tus(M),Pleu

rotus

ostrea

tus,Ra

maria

botrytis,R

amaria

flava

,Rhizo

pogo

nroseolus

,Spa

rassiscrispa

,Suillu

sco

llitin

us,T

richo

lomaac

erbu

m,T

richo

lomapo

rten

tosu

m

IZD=5

28mm

MIC

=5g

/mL30

0mg/mL

[11,15

,31,35

40,44

50,54,

55,71]

Enteroco

ccus

faecalis

Lentinus

edod

esIZD=8mm

[50]

Enteroco

ccus

faecium

Lentinus

edod

esMIC

>1.5>50mg/mL

[54]

Lactob

acillus

casei

Lentinus

edod

esCFU

=5.00

(7.07

)10

19.28

(2

.76)

10

2

MIC

=0.051

5mg/mL

[53,54

,67]

Listeria

inno

cua

Lentinus

edod

esIZD=8mm

[11]

Listeria

mon

ocytog

enes

Lentinus

edod

es,P

ycno

porussang

uine

us(M

),IZD=111

3mm

[11,34

,50]

Stap

hyloco

ccus

sp.

Lentinus

edod

esIZD=12

mm

[50]

Stap

hyloco

ccus

aureus

Agaricus

bisporus

,Aga

ricus

bitorquis,Ag

aricus

essettei,A

garic

ussilvcola,

Armillaria

mellea,

Boletused

ulis,C

antharellusciba

rius,Clito

cybe

geotropa

,Co

rtinariussp.,Co

rtinariusa

bnormis,C

ortin

ariusa

rdesiacu

s,Co

rtinariusarch

eri,Co

rtinariusa

ustroa

lbidus

,Cortin

ariusa

ustrov

enetus

,Cortin

arius

austroviolac

eus,Co

rtinariusc

oelopu

s,Co

rtinariusc

leland

ii,Co

rtinarius[Dermoc

ybesp,D

ermoc

ybeca

naria

,Dermoc

ybeku

la],Co

rtinariusfulvo

iuba

tus,

Cortinariusianthinu

s,Co

rtinariusmem

oria-ann

ae,C

ortin

ariusp

ersp

lend

idus

,Cortin

ariussina

pico

lor,Co

rtinariussu

bmag

ellanicu

s,Co

rtinariustricho

-lomoide

s,Co

rtinariusvino

sipe

s,Gan

odermalucidu

m,H

ydnu

mrepa

ndum

,Hyg

roph

orus

agatho

smus

,Hyp

holomafasciculare,Irp

exlacteu

s(M),La

c-tariu

sca

mph

oratus

,Lac

tariu

sde

licious

,Lac

tariu

spiperatus

,Lac

tariu

svo

lemus

,Lae

tiporus

sulphu

reus

,Len

tinus

edod

es,Lep

ista

nuda

,Leu

copa

xillu

sgiga

nteu

s(M

),Mac

rolepiotaproc

era,

Meripilu

sgigan

teus

(M),Meripilu

sgigan

teus

,Morch

ella

elata(M

),Morch

ella

escu

lentavar.vu

lgaris(M

),Nav

es-

porusfloccosa,

Notho

panu

shyg

roph

anus

(M),Pa

xillu

sinv

olutus

(M),Ph

ellin

usrim

osus

,Pleurotus

eryn

gii(M),Pleu

rotuso

streatus

(M),Pleu

rotuss

ajor-

caju,P

ycno

porussang

uine

us(M

),Ra

maria

botrytis,R

amaria

flava

,Spa

rassiscrispa

,Suillu

sco

llitin

us

CFU

=2.110

4

IZD=8

24mm

MIC

=5g

/mL50

mg/mL

IC50

50

mg/mL

[54]

Stap

hyloco

ccus

saprop

hyti-

cus

Agaricus

cf.n

igrecentulus

(M),Tyromyces

duracinu

s(M)

IZD>12

mm

[34]

Streptoc

occu

spyo

gene

sLentinus

edod

esCFU

=6.010

4[52]

Streptoc

occu

ssalivarius

Lentinus

edod

esMIC

=0.1

10mg/mL

[54]

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Table

1(con

tinue

d)

Microorgan

ism

Mushroom

aRe

sults

References

Streptoc

occu

ssang

uinis

Lentinus

edod

esCFU

=2.53

(0.62

)10

65.06

(1,58

)10

6

MIC

=0.07

550

mg/mL

[53,54

,67]

Streptoc

occu

sso

brinus

Lentinus

edod

esMIC

=0.07

520

mg/mL

[54]

Microco

ccus

flavu

sAg

aricus

bisporus

,Aga

ricus

bitorquis,Ag

aricus

essettei,Lae

tiporus

sulphu

rous

,Ram

aria

flava

IZD=202

31mm

[15,47

,48]

Microco

ccus

luteus

Agaricus

bisporus

,Aga

ricus

bitorquis,Ag

aricus

essettei,C

litoc

ybealexan

dri,La

etiporus

sulphu

rous

,Len

tinus

edod

es,R

amaria

flava

IZD=102

11mm

[15,38

,47,48

,52

]

Sarcinalutea

Armillaria

mellea(M

),Armillaria

mellea,

Clito

cybe

geotropa

,Meripilu

sgigan

teus

(M),Meripilu

sgigan

teus

,Morch

ella

costata(M

),Morch

ella

escu

lenta

var.vu

lgaris(M

),Pa

xillu

sinvo

lutus(M

),Pleu

rotusos

trea

tus(M

),Sp

arassiscrispa

IZD=8

27mm

[35,36

]

aAcetone

,chloroform,ethan

ol,e

thylacetate,metha

nol,dichlorometha

ne,ether,xylen

e,or

water

extracts.M

mycelium,the

othe

rsamples

referto

thefruiting

body

;MRS

Amethicillin-resistan

tStap

hyloco

ccus

aureus.T

hean

timicrobialactivity

isex-

pressedin

CFU

(colon

yform

ingun

ities),M

IC(m

inim

alinhibitory

concen

trations),IZD(in

ternalzone

diam

eter),or

IC50

(con

centration

sinhibiting

50%of

thegrow

th)values

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pro

hibi

ted.The genus Cortinarius is one of the most diverse genera of mush-rooms. Ethyl acetate extracts of C. ardesiacus, C. archeri, C. atro-sanguineus, C. austrovenetus, C. austroviolaceus, C. coelopus, C.[Dermocybe canaria], C. clelandii, C. [D. kula], C. memoria-annae,C. persplendidus, C. sinapicolor, C. vinosipes, and 47 other collec-tion samples not identified to the species level, exhibited IC50 val-ues of 0.09mg/mL against Staphylococcus aureus [10]. However,in a study reported by Ozen et al. [32], Cortinarius sp.methanolicextracts showed lower activity against Staphylococcus aureus.This demonstrates the effect of solvent extraction in the typeand concentration of compounds present in the final extractand, consequently, the spectrum of antimicrobial activity.Ganoderma lucidum is one of the most famous traditional medic-inal mushrooms. Various extracts have been found to be equallyeffective when compared to gentamycin sulphate, the acetoneextract being the most effective. This mushroom had moderateinhibition against Bacillus subtilis and Staphylococcus aureus forany extract [39], but in the study reported by Sheena et al. [40],its methanolic extract showed poor antimicrobial activity. Otherauthors described the capacity of the aqueous extract to inhibit15 types of gram-positive and gram-negative bacteria, with thehighest inhibition exhibited againstMicrococcus luteus [41].Ethyl acetate extracts of Phellinus sp., Gloeoporus thelephoroides,and Hexagonia hydnoides inhibited Bacillus cereus growth, whilethe same extract of Nothopanus hygrophanus mycelium present-ed inhibitory activity against Listeria monocytogenes and Staphy-lococcus aureus. Irpex lacteus mycelium extract was the most ef-fective, presenting a broad spectrum of activity [34].The antimicrobial activity of Pycnoporus sanguineus has beenknown since 1946, when Bose isolated poliporin, a compound ac-tive against gram-positive and gram-negative bacteria and with-out toxicity in experimental animals. Rosa et al. reported inhibi-tion against Listeria monocytogenes and Staphylococcus aureus[34]. Smnia et al. [42,43] showed that this mushroom producescinnabarine, an orange pigment active against Bacillus cereus,Staphylococcus aureus, Leuconostoc mesenteroides, Lactobacillusplantarum, and several Streptococcus spp. Cinnabarine was moreactive against gram-positive than gram-negative bacteria [34].The chloroform extract ofHygrophorus agathosmus and dichloro-methane of Suillus collitinus were active against all the testedgram-positive bacteria. The highest antibacterial activity wasseen in the extract of H. agathosmus against Staphylococcus epi-dermidis and Bacillus subtilis, with MIC values 7.81 g/mL lowerthan the reference antibiotic streptomycin (MIC = 15.62 g/mL).MIC values (15.62 g/mL) against Staphylococcus aureus wereequal to the ones of streptomycin. Suillus collitinus showed MICvalues much higher than the standard [44].One nonedible mushroom, Hypholoma fasciculare (methanolicextract), presented high antimicrobial activity against gram-pos-itive bacteria, namely Bacillus cereus, Bacillus subtilis, and Staph-ylococcus aureus [37].All the tested gram-positive bacteria were susceptible to metha-nolic extracts of Lactarius species and Tricholoma portentosum[32,45,46]. Among Lactarius species (L. piperatus, L. camphorates,L. volemus, L. delicious), L. camphoratus methanolic extract wasthe one with greater antimicrobial activity [32]. Methanolic ex-tracts of Ramaria botrytis and the ethanolic extract of Ramariaflava inhibited the growth of gram-positive bacteria better thangram-negative bacteria [47]. The antimicrobial effect of the etha-nolic extract of Laetiporus sulphureus was tested by Turkoglu etal. [48] and strongly inhibited the growth of the gram-positiveAlves MJ et al. A Review on Planta Med 2012; 78: 17071718

ive

c)hirdo

pesisnd

and

irtu

andth- ACornardo

1712 Reviews

tion

is st

rictly

pro

hibi

ted.Table 2 Mushroom compounds with antimicrobial activity against gram-posit

Microorganism Compound (mushroom)

Bacillus cereus Confluentin (1a), Grifolin (1b) and Neogrifolin (1nosta-8,24(Z)-diene-26-oic acid (2) (JahnoporusedodesM); Proteins and peptides: Plectasin (Pseu

Bacillus subtilis Peptides: Peptaibol Boletusin, Peptaibol Chrysosspermin 5 (Boletus spp.); Protein (Cordyceps sinen(4ad) (Flammulina velutipesM); Ganomycin A a

Bacillus thuringiensis Plectasin (Pseudoplectania nigrella)

Corynebacterium diphtheriae Plectasin (Pseudoplectania nigrella)

Corynebacterium jeikeium Plectasin (Pseudoplectania nigrella)

Corynebacterium lilium Peptaibol Boletusin, Peptaibol Chrysospermin 3(Boletus spp.)

Enterococcus faecalis 1a, 1b and 1c (Albatrellus flettii); 2 (Jahnoporus hgrella)

Enterococcus faecium; VREF Plectasin (Pseudoplectania nigrella)

Micrococcus flavus 5a, b (Ganoderma pfeifferi)

Staphylococcus aureus Peptaibol Boletusin, Peptaibol Chrysospermin 3(Boletus spp.); Proteins (Cordyceps sinensis); 6-Meether (7), (1S,3S)-Austrocortilutein (8a), (1S,3R)Austrocortirubin (8c) andTorosachrysone (8 d) ((9a), Erythroglaucin (9b) and Emodin (9c) (CortitipesM); 5a, b (Ganoderma pfeifferi); 3 (Lentinus ebacteria tested, including Bacillus subtilis, Bacillus cereus, Micro-coccus luteus, andMicrococcus flavus.The Lepista nuda methanolic extract had a good action on gram-positive bacteria, more specifically on Bacillus cereus, Bacillussubtilis, and Staphylococcus aureus [37,49].Ishikawa et al. reported the inhibitory activity of Lentinus edodesethyl acetate extract against Bacillus cereus, Bacillus subtilis,Staphylococcus aureus, and Staphylococcus epidermidis [11]. Thismushroom (aqueous extract) as well as the n-BuOH fraction ofthe Phellinus linteus methanol extract demonstrated good activ-ity against MRSA [50,51]. Furthermore, Streptococcus pyogeneswas very sensitive to the Lentinus edodes chloroform extract[52]. The ability of L. edodes extracts to improve oral health hasalso been extensively researched, since it showed a strong bacter-icidal effect upon Streptococcus mutans, which is strongly impli-cated in dental caries and tooth decay [53,54].The mycelium of Leucopaxillus giganteus (methanolic extract)presented antimicrobial capacity, inhibiting only gram-positivebacteria and, in decreasing order, Staphylococcus aureus > Bacilluscereus > Bacillus subtilis [55]. The authors stated that the mostpromising nitrogen source to produce mushrooms with an in-creased content in bioactive compounds that inhibit gram-posi-tive bacteria growth was (NH4)2HPO4.

sajor-caju); Plectasin (Pseudoplectania nigrella);FractColoratin A (10) (Xylaria intracolarata)

MRSA Plectasin (Pseudoplectania nigrella);

Staphylococcus epidermidis;MRSE

Plectasin (Pseudoplectania nigrella)

Streptococcus sp. Peptaibol Chrysospermin 3 (Boletus spp.)

Streptococcus faecalis 3 (Lentinus edodesM.)

Streptococcus group A, B, C, G Fraction B (Pycnoporus sanguineus)

Streptococcus pneumonia;PRSP


Streptococcus pyogenes;ERSP


M mycelium, the other samples refer to the fruiting body. The antimicrobial activity is exp

or IC50 (concentrations inhibiting 50% of the growth) values. VREF vancomycin-resistant E

MRSE methicillin-resistant Staphylococcus epidermidis; PRSP penicillin-resistant Streptococ

Alves MJ et al. A Review on Planta Med 2012; 78: 17071718bacteria.

Results Refer-

ences

(Albatrellus flettii); 3,11-Dioxola-tus); Oxalic acid (3) (Lentinusplectania nigrella)

IZD = 17mmMIC = 10 g/mL 128mg/L

[56,59,63]

rmin 3 and Peptaibol Chryso-); Enokipodins A, B, C and DB (5a, b) (Ganoderma pfeifferi)

MIC > 100000 g/LIZD = 1128mm

[57,58,61,64]

MIC = 0.5mg/L [63]

MIC = 8mg/L [63]

MIC = 2mg/L [63]

Peptaibol Chrysospermin 5 IZD = 2325mm [64]

s); Plectasin (Pseudoplectania ni- MIC = 0.5 g/mL 128mg/L [56,63]

MIC = 3264mg/L [63]

IZD = 2526mm [57]

Peptaibol Chrysospermin 5ylxanthopurpurin-3-O-methylustrocortilutein (8b), (1S,3S)-tinarius basirubencens); Physcionius sp.); 4ad (Flammulina velu-desM); Ribonuclease (Pleurotus

IZD = 1224mmMIC = 0.156mg/L50000 g/LIC50 = 0.7> 50 g/mLIC50 = 34 4 M

[10,42,5764]Themethanolic extracts of Phellinus rimosus andNavesporus floc-cosa showed moderate inhibition of Bacillus subtilis and Staphy-lococcus aureus [40].Pleurotus ostreatus and Meripilus giganteus showed broad-spec-trum antimicrobial activity. The maximum effect was shown bythe ethanolic extracts of Pleurotus ostreatus against Sarcina lutea[35].The ether extract of Pleurotus sajor-caju showed high antibacte-rial activity against Staphylococcus aureus, whereas Staphylococ-cus epidermidis showed high sensitivity for the ethanol extract[33].Overall, it should be pointed out that the most susceptible gram-positive bacteria to mushroom inhibitory action are Staphyloco-cos aureus, Bacillus cereus, and Bacillus subtilis. Agaricus bisporus[15,32,33], Agaricus bitorquis [15], Boletus edulis [31,32], Can-tharellus cibarius [31,32,37], Lentinus edodes [11,50,54], and dif-ferent Cortinarius sp. [10] seem to be a good option to inhibitStaphylococos aureus, and in some cases, Bacillus cereus and Bacil-lus subtilis. Studies with microorganisms related to nosocomialinfections andmultiresistance cases such as Enterococcus faecalis,Enterococcus faecium, and MRSA are scarce. Nevertheless, in thefew studies available, Lentinus edodes [50] was reported to inhibitEnterococcus faecalis, Enterococcus faecium, and MRSA. The latter

ion B (Pycnoporus sanguineus);

MIC = 32mg/L [63]

MIC = 8mg/L [63]

IZD = 9mm [60]

IZD = 13mm [59]

MIC = 0.0190.039mg/mL [42]

MIC = 0.5mg/L [63]

MIC = 0.125mg/L [63]

ressed in MIC (minimal inhibitory concentrations), IZD (internal zone diameter),

nterococcus faecium; MRSA methicillin-resistant Staphylococcus aureus;

cus pneumonia; ERSP erythromycin- resistant Streptococcus pyogenes

This

doc

umen

t was

dow

nloa

ded

for p

erso

nal u

se o

nly.

Una

utho

rized

dist

ribu

gram-negative bacteria tested, with Proteus vulgaris being the

1713Reviews

This

doc

umen

t was

dow

nloa

ded

for p

erso

nal u

se o

nly.

Una

utho

rized

dist

ribut

ion

is st

rictly

pro

hibi

ted.microorganism was also inhibited by Phellinus linteus [51] andPleurotus ostreatus [50]. It is important to develop new studieswith different mushroom species and, moreover, with these mi-croorganisms that are so problematic to human health.

Antimicrobial compounds from mushroomsMost studies on mushrooms with antibacterial activity describethe action of its extracts without identifying the compounds re-sponsible for this activity. However, some compounds have beendescribed as active against gram-positive bacteria (l" Table 2).Five of these compounds are terpenes. Confluentin (1a), grifolin(1b), and neogrifolin (1c) from Albatrellus fletti showed activityagainst Bacillus cereus and Enterococcus faecalis. The best resultwas for Enterococcus faecalis (MIC 0.5 to 1.0mg/mL) [56]. Gano-mycin A and B (5 a, b), isolated from Ganoderma pfeifferi, showedactivity against Bacillus subtilis, Micrococcus flavus, and Staphylo-coccus aureus (1525mm zones of inhibition at a concentrationof 250 g/mL [57].A steroid, 3,11-dioxolanosta-8,24(Z)-diene-26-oic acid (2), wasisolated from the Jahnoporus hirtus mushroom and revealed ac-tivity against Bacillus cereus and Enterococcus faecalis [56].Four sesquiterpenes with antimicrobial activity were described.The enokipodins A, B, C, and D (4ad), isolated from the myce-lium of Flammulina velutipes, with activity against Bacillus subti-lis, but only enokipodins A and C showed activity against Staph-ylococcus aureus [58].Oxalic acid (3), an organic acid, isolated from the mycelium ofLentinus edodes, showed activity against Bacillus cereus, Staphylo-coccus aureus, and Streptococcus faecalis [59].Coloratin A (10), a benzoic acid derivative isolated from Xylariaintracolarata, inhibited Staphylococcus aureus [60].Eight compounds anthraquinone derivatives were also reporteddue to their antibacterial activities. 6-Methylxanthopurpurin-3-O-methyl ether (7), (1S,3S)-austrocortilutein (8a), (1S,3R)-austro-cortilutein (8b), (1S,3S)-austrocortirubin (8c), and torosachry-sone (8 d), isolated from the mushroom Cortinarius basiruben-cens, and physcion (9a), erythroglaucin (9b), and emodin (9c),isolated from other species of Cortinarius, were all effectiveagainst Staphylococcus aureus [10].In addition to the LMW compounds already mentioned, severalantimicrobial compounds with HMW have also been described,in particular, proteins and peptides.CSAP (Cordyceps sinensis antibacterial protein-N-terminal se-quence ALATQHGAP), isolated from Cordyceps sinensis, showedstrong activity against Staphylococcus aureus and poor activityagainst Bacillus subtilis. However, the antibacterial action of thisprotein was bacteriostatic [61].The ribonuclease isolated from Pleurotus sajor-caju showed ac-tivity against Staphylococcus aureus, acting on RNA [62].The peptide plectasin, isolated from Pseudoplectania nigrella, is amacromolecule belonging to the class of defensins, present in an-imals and plants, which acts at the cell wall, more specifically inthe synthesis of peptidoglycan. This peptide showed activityagainst Bacillus cereus, Bacillus thuringiensis, Corynebacteriumdiphtheriae, Corynebacterium jeikeium, Enterococcus faecalis, En-terococcus faecium, VREF, Staphylococcus aureus,MRSA, Staphylo-coccus epidermidis, MRSE, Streptococcus pneumonia, PRSP, andStreptococcus pyogenes. The in vitro action of plectasin againstStreptococcus pneumoniae is comparable to the action of penicil-lin and vancomycin [63].The peptides peptaibol boletusin, pepteibol chrysospermin 3,

and peptaibol chrysospermin 5 (isolated from Boletus spp.) allowmost sensitive [36].Beatttie et al. [10] reported anti-Pseudomonas aeruginosa activityof the genus Cortinarius and its subgenus, Dermocybe (metha-nolic extracts). Four species were tested, namely C. abnormis, C.austroalbidus, C. [D. kula], C. persplendidus, and eleven Cortinar-ius collection samples not identified to the species level, obtain-ing IC50 values 0.09mg/mL against P. aeruginosa.The acetone extract from Ganoderma lucidum showed strongantibacterial activity, mainly against Klebsiella pneumonia [39].Further studies indicate that the antimicrobial combination of G.lucidum extracts with chemotherapeutic agents (ampicillin, cefa-for the opening of pores for ion transport, and showed activityagainst Bacillus subtilis, Corynebacterium lilium, and Staphylococ-cus aureus. The peptaibol chrysospermin 3 also showed activityagainst Streptococcus sp. [64].Fraction B from Pycnoporus sanguineus, obtained by Smnia et al.[42], whose main constituent is a phenoxazin-3-one-type pig-ment, showed activity against Staphylococcus aureus and Strepto-coccus A, B, C, and G. Lower values of MIC were obtained againstStreptococcus strains.The mechanisms of action of most of the compounds describedabove are not available in the literature.

Antimicrobial Activity Against Gram-Negative Bacteria!

MethodologiesThe same methodologies already described for gram-positivebacteria are also used in the evaluation of mushroom extracts orcompounds antimicrobial activity against gram-negative bacte-ria. The results are presented in l" Tables 3 and 4.

Mushroom extracts with antimicrobial activityThe antimicrobial activity against gram-negative bacteria shownby different mushroom extracts is not so extensive and is shownin l" Table 3.The results for Agaricus bisporus are contradictory. Barros et al.[31] and ztrk et al. [15] found no activity against gram-nega-tive bacteria, while Ozen et al. [32] and Tambeker et al. [33] re-ported positive activity mainly against Escherichia coli, but alsoagainst Pseudomonas aeruginosa, Enterobacter aerogenes, Kleb-siella pneumoniae, Proteus vulgaris, Salmonella typhi, and Salmo-nella typhimurium. However, these divergences may be due todifferent methods and concentrations used. Agaricus bitorquismethanolic extract had some effects against three of the gram-negative bacteria, namely Yersinia enterocolitica, Klebsiella pneu-moniae, and Proteus vulgaris [15]. Agaricus essettei, Agaricus silvi-cola, Agaricus silvaticus, and Agaricus cf. nigrecentulus did notshow any antibacterial activity against gram-negative bacteria[15,31,34].Ethanolic extracts of Armillaria mellea fruiting bodies revealedbetter antimicrobial activity than chloroform extracts and myce-lium extract upon gram-negative bacteria [35,36].According to Barros et al. [31,37], Cantharellus cibarius showedno activity against gram-negative bacteria, as opposed to Ozenet al. [32], who reported there was activity against Escherichiacoli and Pseudomonas aeruginosa.Enterobacter aerogenes and Escherichia coliwere inhibited by themethanolic extract of Clitocybe alexandri [38]. Clitocybe geotropachloroform and ethanolic extracts inhibited the growth of allzolin, oxytetracycline, and chloramphenicol) resulted in syner-


Table

3Mushroo

mextractswithan

timicrobialactivity

againstgram

-neg

ativeba

cteria.

Microorgan

ism

Mushroom

aResults

References

Cupriavidis

Lentinus

edod

esIZD=15

mm

[50]

Enteroba

cter

aeroge

nes

Agaricus

bisporus

,Clitoc

ybealexan

dri,Hyg

roph

orus

agatho

smus

,Meripilu

sgigan

teus

(M),Pa

xillu

sinv

olutus

(M),Pleu

rotusos

trea

tus(M

),Pleu

rotussajor-ca

ju,R

hizo

pogo

nroseolus

,Suillu

sco

llitin

usIZD=8

22mm

MIC

=15

.62

125g

/mL

[33,35

,38,44

]

Enteroba

cter

cloa

cae

Armillaria

mellea,

Clito

cybe

geotropa

,Meripilu

sgiga

nteu

s(M

),Meripilu

sgigan

teus

,Pax

illus

invo

lutus(M

),Pleu

rotusos

trea

tus(M

),Sp

arassiscrispa

IZD=102

0mm

[35,36

]

Enteroba

cter

faecalis

Armillaria

mellea,

Clito

cybe

geotropa

,Meripilu

sgiga

nteu

s(M

),Meripilu

sgigan

teus

,Spa

rassiscrispa

IZD=8

14mm

[35,36

]

Esch

erichiaco

liAg

aricus

bisporus

,Arm

illaria

mellea(M

),Armillaria

mellea,

Boletused

ulis,C

antharellusciba

rius,Clito

cybe

alexan

dri,Clito

cybe

geotropa

,Co

rtinariussp.,Gan

odermalucidu

m,H

ydnu

mrepa

ndum

,Irpex

lacteu

s(M

),La

ctariusca

mph

oratus

,Lac

tariu

sde

licious

,Lac

tariu

spipe

ra-

tus,La

ctariusvo

lemus

,Lae

tiporus

sulphu

reus

,Len

tinus

edod

es,Lep

ista

nuda

,Leu

coag

aricus

cf.cinereu

s(M

),Mac

rolepiotaproc

era,

Mar-

asmiussp.(M),Marasmiuscf.b

ellus(M

),Meripilu

sgigan

teus

(M),Meripilu

sgiga

nteu

s,Morch

ella

costata(M

),Morch

ella

horten

sis(M

),Nav

espo

rusflo

ccosa,

Paxillu

sinvo

lutus(M

),Ph

ellin

usrim

osus

,Pleurotus

eryn

gii(M),Pleu

rotusos

trea

tus(M

),Pleu

rotussajor-ca

ju,R

hizo

-po

gonroseolus

,Spa

rassiscrispa

,Suillu

sco

llitin

us

IZD=8

27.400.19

mm

MIC

=25

0g

/mL>50

mg/mL

[32

36,38

40,44,

46,48

50,54,71

]

Fuso

bacterium

nuclea

tum

Lentinus

edod

esCFU

=2.40

(3.11

)10

27.56

(4.28

)10

6

MIC

=0.9

20mg/mL

[53,54

,67]

Kleb

siella

aeroge

nes

Lentinus

edod

esIZD=9mm

[50]

Kleb

siella

pneu

mon

iae

Agaricus

bisporus

,Aga

ricus

bitorquis,Gan

odermalucidu

m,Lac

tariu

spipe

ratus,Lentinus

edod

es,Lep

ista

nuda

,Pleurotus

sajor-ca

ju,

Ramaria

flava

IZD=4

31.600.10

mm

MIC

=0.5mg/mL

[11,15

,33,39

,46,

47,49,50

,55]

Morga

nella

morga

nii

Agaricus

bisporus

,Aga

ricus

bitorquis,Ag

aricus

essettei,Lae

tiporus

sulphu

rous

IZD=4.50.5mm

[15,48

]

Neisseria

subflava

Lentinus

edod

esCFU

=9.49

(2.60

)10

61.50

(0,50

)10

8[53,67

]

Porphy

romon

asging

ivalis

Lentinus

edod

esMIC

=0.051

0mg/mL

[45]

Prevotella

interm

edia

Lentinus

edod

esCFU

=2.00

(2.83

)10

12.60

(6.66

)10

5

MIC

=0.051

5mg/mL

[53,54

,67,68

]

Prevotella

nigrescens

Lentinus

edod

esMIC

=0.1

15mg/mL

[54]

Proteu

smira

bilis

Lentinus

edod

esIZD=4mm

[11]

Proteu

svu

lgaris

Agaricus

bisporus

,Aga

ricus

bitorquis,Armillaria

mellea,

Clito

cybe

geotropa

,Lae

tiporus

sulphu

reus

,Meripilu

sgiga

nteu

s(M

),Meripilu

sgiga

nteu

s,Pleu

rotusos

trea

tus(M

),Pleu

rotussajor-ca

ju,S

parassiscrispa

IZD=5.50.5

19mm

[15,33

,35,36

,48]

Pseu

domon

asae

rugino

saAg

aricus

bisporus

,Boletus

edulis,C

antharellusciba

riusC

ortin

ariussp.,Co

rtinariusa

bnormis,C

ortin

ariusa

rdesiacu

s,Co

rtinariusarch

eri,

Cortinariusa

ustroa

lbidus

,Cortin

ariusa

ustrov

enetus

,Cortin

ariusa

ustrov

iolaceus

,Cortin

ariusco

elop

us,C

ortin

ariusclelan

dii,Co

rtinarius

[Dermoc

ybesp.,Dermoc

ybeca

naria

,Dermoc

ybeku

la],Co

rtinariusfulvoiub

atus

,Cortin

ariusianthinu

s,Co

rtinariusmem

oria-ann

ae,C

or-

tinariusp

ersp

lend

idus

,Cortin

ariuss

inap

icolor,C

ortin

ariuss

ubmag

ellanicu

s,Co

rtinariust

richo

lomoide

s,Co

rtinariusv

inos

ipes,G

anod

erma

lucidu

m,H

ydnu

mrepa

ndum

,Lac

tariu

sca

mph

oratus

,Lac

tariu

sde

licious

,Lac

tariu

spipe

ratus,La

ctariusvo

lemus

,Lae

tiporus

sulphu

reus

,Lentinus

edod

es,Lep

ista

nuda

,Mac

rolepiotaproc

era,

Nav

espo

rusflo

ccos

a,Ph

ellin

usrim

osus

,Pleurotus

sajor-ca

ju,R

amaria

flava

IZD=6

20mm

MIC

=0.5

100mg/mL

IC50=0.04

>2.00

mg/mL

[10,32

,33,39

,40,

45,46,485

0]

Pseu

domon

asmaltoph

ilaLentinus

edod

esIZD=6mm

[11]

Salm

onella

enteritidis

Laetiporus

sulphu

reus

,Ram

aria

flava

IZD=4

51mm

[37,40

]

Salm

onella

poon

aLentinus

edod

esIZD=9mm

[50]

Salm

onella

typh

iAg

aricus

bisporus

,Gan

odermalucidu

m,P

leurotus

sajor-ca

juIZD=7.00

0.182

0.60

0.14

mm

[33,39

]

Salm

onella

typh

imurium

Agaricus

bisporus

,Arm

illaria

mellea(M

),Armillaria

mellea,

Clito

cybe

geotropa

,Gan

odermalucidu

m,H

ygroph

orus

agatho

smus

,Irpex

lac-

teus

(M),Lepistanu

da,M

eripilu

sgigan

teus

(M),Meripilu

sgigan

teus

,Morch

ella

costata(M

),Morch

ella

elata(M

),Morch

ella

escu

lentavar.

vulgaris(M

),Morch

ella

horten

sis(M

),Nav

espo

rusflo

ccosa,

Paxillu

sinvo

lutus(M

),Ph

ellin

usrim

osus

,Pleurotus

ostrea

tus(M

),Pleu

rotus

sajor-ca

ju,S

parassiscrispa

,Suillu

sco

llitin

us,

IZD=6

16mm

MIC

=15

.62

125g

/mL

[33

36,40,44

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d.Table 4 Mushroom compounds with antimicrobial activity against gram-nega

Microorganism Compound (mushroom)

Achromobacter xyloxidans 6 (Leucopaxillus albissimus)

Acinetobacter baumannii 6 (Leucopaxillus albissimus)

Agrobacterium rhizogenes Protein (Clitocybe sinopica)

Agrobacterium tumefaciens Protein (Clitocybe sinopica)

Agrobacterium vitis Protein (Clitocybe sinopica)

Burkholderia cenocepacia 6 (Leucopaxillus albissimus)

Burkholderia cepacia 6 (Leucopaxillus albissimus)

Burkholderia multivorans 6 (Leucopaxillus albissimus)

Cytophaga johnsonae 6 (Leucopaxillus albissimus)

Escherichia coli Proteins (Cordyceps sinensis); 5a, b (GanodermFraction B (Pycnoporus sanguineus); 10 (Xylar

Klebsiella pneumoniae 3 (Lentinus edodesM); Fraction B (Pycnoporus10 (Xylaria intracolarata)

Proteus mirabilis 5a, b (Ganoderma pfeifferi)

Proteus vulgaris Protein (Cordyceps sinensis); 3 (Lentinus edode

Pseudomonas aeruginosa 7, 8a-8 d (Cortinarius basirubencens); 9ac (C3 (Lentinus edodesM); 6 (Leucopaxillus albissimRibonuclease (Pleurotus sajor-caju); Fraction B10 (Xylaria intracolarata)

Pseudomonas fluorescens 3 (Lentinus edodesM); Ribonuclease (Pleurotu

Serratia marcescens 5a, b (Ganoderma pfeifferi)

Salmonella enteritidis 10 (Xylaria intracolarata)

Salmonella typhi Protein (Cordyceps sinensis); Fraction B (Pycno

Stenotrophomonas maltophilia 6 (Leucopaxillus albissimus)

Xanthomonas malvacearum Protein (Clitocybe sinopica)

Xanthomonas oryzae Protein (Clitocybe sinopica)gism or antagonism, with synergism observed when combinedwith cefazolin against Bacillus subtilis and Klebsiella oxytoca [40,65].The mycelium extract from Leucoagaricus cf. cinereus, Marasmiuscf. bellus, and Marasmius sp. were capable of inhibiting thegrowth of Escherichia coli. Within the family Tricholomataceae,species from the genusMarasmius have long been known to pro-duce interesting secondary metabolites [66].The Hydnum repandum methanolic extract was mainly activeagainst Pseudomonas aeruginosa. Escherichia coli was found tobe the most sensitive bacteria to methanolic extracts of Lactariusspecies [32]. However, no activity of Lactarius delicious against E.coliwas observed [45,46].The Laetiporus sulphureus ethanolic extract had a lower antibac-terial spectrum against gram-negative bacteria, having no activ-ity against Klebsiella pneumonia [48].On three occasions, namely with the Pseudomonas sp., Lentinusedodes aqueous extract was significantly more active than cipro-floxacin (positive control), whereby it gave markedly greaterzones of inhibition. This result is of important clinical signifi-cance, as P. aeruginosa is emerging as a major etiological of thenosocomial infection [50]. L. edodes mycelium had no effect onEscherichia coli, Pseudomonas fluorescens, Klebsiella pneumoniae,and Camphylobacter jejuni [52].Extracts from Lentinus edodes showed a strong bactericidal effectagainst Prevotella intermedia, which is associated with gingivitis.This mushroom was capable of significantly reducing dentalplaque deposition [53,54,67,68].

M mycelium, the other samples refer to the fruiting body. The antimicrobial activity is expr

(concentrations inhibiting 50% of the growth) valuesbacteria.

Results References

MIC = 32 g/mL [69]

MIC = 128 g/mL [69]

MIC = 0.14 M [70]

MIC = 0.14 M [70]

MIC = 0.28 M [70]

MIC = 16 g/mL [69]

MIC = 32 g/mL [69]

MIC = 16 g/mL [69]

IZD = 16mm [69]

pfeifferi);tracolarata)

IZD = 416mmMIC = 0.625mg/mL100000 g/L

[42,57,60,61]

guineus); IZD = 1222mmMIC = 0.625mg/mL

[42,59,60]

IZD = 15mm [57]

) IZD = 12mmMIC = 75000 g/L

[59,61]

inarius sp.););ycnoporus sanguineus);

IZD = 1516mmMIC = 128 g/mL1.250mg/mLIC50 = 1.5> 50 g/mLIC50 = 51 6 M

[10,42,59,62,64,68]

jor-caju) IZD = 13mmIC50 = 186 12 M

[59,62]

IZD = 1516mm [57]

IZD = 16mm [60]

rus sanguineus) MIC = 0.312mg/mL 50000 g/L [42,61]

MIC = 32 g/mL [69]

MIC = 0.56 M [70]

MIC = 0.56 M [70]The Lepista nuda methanolic extract was effective against Esche-richia coli and Pseudomonas aeruginosa [49].Tambeker et al. [33] reported the antimicrobial ability of severalextracts of Pleurotus sajor-caju. Escherichia coli, Enterococcusaerogenes, Pseudomonas aeruginosa, and Klebsiella pneumoniaewere most sensitive to ethanolic, methanolic, and xylene ex-tracts.Overall, among the tested gram-negative bacteria, Escherichia coliand Klebsiella pneumoniae are the most susceptible to mush-rooms inhibitory effect. Agaricus bisporus [32,33], Lentinus edo-des [50,54], Ganoderma lucidum [39,40], and Lepista nuda [49]seem to have higher antimicrobial activity against those microor-ganisms. Pseudomonas aeruginosa was inhibited by Clitocybealexandri [38], Boletus edulis, Cantharellus cibarius [32], Ganoder-ma lucidum [39], and Cortinarius sp. [10] extracts. Studies withEnterobacter aerogenes and Serratia marcescens are scarce, anddue to the importance in the area of multiresistance, they shouldbe carrried out to assess sensibility to extracts from mushroomspecies.

Antimicrobial compounds from mushroomsSome of the compounds previously discussed have also been de-scribed for their action against gram-negative bacteria (l" Table4).Terpenes 5a and 5b, isolated from Ganoderma pfeifferi, showedmoderate activity against Escherichia coli, Proteus mirabilis, andSerratia marcescens [57].

essed in MIC (minimal inhibitory concentrations), IZD (internal zone diameter), or IC50


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Ribonuclease (Pleurotus sajor-caju) showed activity against Pseu-domonas aeruginosa and Pseudomonas fluorescens, acting at the

UI0690/2011 and project PEst-OE/EQB/LA0016/2011. It was alsosupported by CHTAD Hospital Center of Trs-os-Montes e Alto

antibacterial activity of Australian basidiomycetous macrofungi usinga high-throughput 96-well plate assay. Pharm Biol 2011; 49: 19

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ted.RNA level [62].Fraction B (Pycnoporus sanguineus) showed activity against Esch-erichia coli, Klebsiella pneumoniae, Pseudomonas aeruginosa, andSalmonella typhi [42].Unfortunatly, the mechanism of action of each one of the isolatedcompounds is not completly clear and described in the availablereports.

Concluding Remarks!

The present review focuses on the antimicrobial effects of mush-rooms from all over the world, and their isolated compounds. Itwill certainly be useful for future scientific studies. Both edibleand nonedible mushrooms showed antimicrobial activity againstpathogenic microorganisms, including bacteria associated withnosocomial infections (Pseudomonas aeruginosa, Pseudomonasmaltophila, Listeria monocytogenes, Staphylococcus aureus, Kleb-siella pneumoniae, Morganella morganii, Proteus mirabilis, Serra-tia marcescens) and multiresistance (MRSA, MRSE, VREF, PRSP,ERSP).Data available from the literature indicates that mushroom ex-tracts and isolated compounds exhibit higher antimicrobial ac-tivity against gram-positive than gram-negative bacteria. Amongall the mushrooms, Lentinus edodes is the best-studied speciesand seems to possess broad antimicrobial action against bothgram-positive and gram-negative bacteria. Species from the gen-era Boletus, Ganoderma, and Lepista appear promising for futurestudies, if one considers the positive activity and limited numberof publications. Considering the low number of studies with indi-vidual compounds, Plectasin peptide, isolated from Pseudoplecta-nia nigrella, revealed the highest antimicrobial activity againstgram-positive bacteria.The comparison of the results reported by different authors is dif-The organic acid 3, isolated from the mycelium of Lentinus edo-des, showed activity against Klebsiella pneumoniae, Proteus vulga-ris, Pseudomonas aeruginosa, and Pseudomonas fluorescens [59].The benzoic acid derivative 10, isolated from Xylaria intracolara-ta, showed activity against Escherichia coli, Klebsiella pneumonia,Pseudomonas aeruginosa, and Salmonella enteritidis. For thiscompound, the highest inhibition (22mm) was found in Klebsiel-la pneumonia, which is higher than the control (gentamicin,14mm) [60].Compounds 7, 8ad (Cortinarius basirubescens), and 9ac (Corti-narius spp.) were effective against Pseudomonas aeruginosa [10].The quinoline 6, isolated from Leucopaxillus albissimus, showedactivity against Achromobacter xyloxidans, Acinetobacter bau-mannii, Burkholderia cenocepacia, Burkholderia cepacia, Burkhol-deria multivorans, Cytophaga johnsonae, and Pseudomonas aeru-ginosa. Among the thirteen microorganisms tested, Cytophagajohnsonaewas the most strongly inhibited (16mm) [69].Some proteins have also been reported against gram-negativebacteria. The protein CSAP, isolated from Cordyceps sinensis andalready mentioned above, showed activity against Escherichiacoli, Proteus vulgaris, and Salmonella typhi [61], while the protein(N-terminal sequence SVQATVNGDKML) isolated from Clitocybesinopicawas active against Agrobacterium rhizogenes, Agrobacte-rium tumefaciens, Agrobacterium vitis, Xanthomonas malvacea-rum, and Xanthomonas oryzae [70].ficult, due to the diverse methodologies used to evaluate antimi-

Alves MJ et al. A Review on Planta Med 2012; 78: 170717182 Kala P. Chemical composition and nutritional value of European spe-cies of wild growing mushrooms: A review. Food Chem 2009; 113: 916

3 Borchers A, Keen CL, Gershwin ME.Mushrooms, tumors, and immunity:an update. Exp Biol Med 2004; 229: 393406

4 Lindequist U, Niedermeyer THJ, Jlich WD. The pharmacological poten-tial of mushrooms. eCAM 2005; 2: 285299

5 Poucheret P, Fons F, Rapior S. Biological and pharmacological activity ofhigher fungi: 20-Year retrospective analysis. Mycologie 2006; 27: 311333

6 Zaidman BZ, Yassin M, Mahajana J, Wasser SP. Medicinal mushroommodulators ofmolecular targets as cancer therapeutics. Appl MicrobiolBiotechnol 2005; 67: 453468

7 Moradali MF, Mostafavi H, Ghods S, Hedjaroude GA. Immunomodulatingand anticancer agents in the realm of macromycetes fungi (macrofun-gi). Int Immunopharmacol 2007; 7: 701724

8 Zhang M, Cui SW, Cheung PCK, Wang Q. Antitumor polysaccharidesfrom mushrooms: a review on their isolation process, structural char-acteristics and antitumor activity. Trends Food Sci Technol 2007; 18:419

9 Wasser SP, Weis AL. Medicinal properties of substances occurring inhigher Basidiomycetes mushrooms: Current perspectives (Review).Int J Med Mushrooms 1999; 1: 3162

10 Beattie KD, Rouf R, Gander L, May TW, Ratkowsky D, Donner CD, Gill M,Grice ID, Tiralongo E. Antibacterial metabolites from Australian macro-Douro and Siemens.

Conflict of Interest!

The authors have no conflicts of interest.

References1 Bala N, Aitken EAB, Fechner N, Cusack A, Steadman KJ. Evaluation ofcrobial activity of mushroom extracts or isolated compounds.Therefore, the standardization of methods and establishment ofcut-off values is urgent. The knowledge about the mechanismsof action of different compounds might lead to the discovery ofnew active principles for antimicrobial activity. Furthermore,the application of cytotoxicity assays is also important to evaluatethe effects on humans in the range of the in vitro tested concen-trations.The research onmushrooms is extensive and hundreds of specieshave demonstrated a broad spectrum of pharmacological activ-ities, including antimicrobial activity. Although there are a num-ber of studies available in the literature, they are almost entirelyfocused on the screening of antibacterial properties of mushroomextracts. In fact, there is a gap in the identification of the individ-ual compounds responsible for those properties, and only a fewlow-molecular weight compounds and some peptides and pro-teins have been described. After elucidation of their mechanismof action, these mushroom metabolites or other related com-pounds could be used to develop nutraceuticals or drugs effectiveagainst pathogenic microorganisms resistant to conventionaltreatments.

Acknowledgments!

This work was funded by Fundao para a Cincia e a Tecnologia(FCT, Portugal) and COMPETE/QREN/EU (research project PTDC/AGRALI/110062/2009; CIMO strategic project PEst-OE/AGR/fungi from the genus Cortinarius. Phytochemistry 2010; 71: 948955

36 Kalyoncu F, Oskay M. Antimicrobial activities of four wild mushroom

1717Reviews

This

doc

umen

t was

dow

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ded

for p

erso

nal u

se o

nly.

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utho

rized

dist

ribut

ion

is st

rictly

pro

hibi

ted.11 Ishikawa NK, Kasuya MCM, Vanetti MCD. Antibacterial activity of Lenti-nula edodes grown in liquid medium. Braz J Microbiol 2001; 32: 206210

12 Shittu OB, Alofe FV, Onawunmi GO, Ogundaini AO, Tiwalade TA.Mycelialgrowth and antibacterial metabolite production by wild mushrooms.Afr J Biomed Res 2005; 8: 157162

13 Suay I, Arenal F, Asensio FJ, Basilio A, Cabello MA, Dez MT, Garca JB, DelVal AG, Gorrochategui J, Hernndez P, Pelez F, Vicente MF. Screening ofbasidiomycetes for antimicrobial activities. Antonie van Leeuwenhoek2000; 78: 129139

14 Gonalves O, Pereira R, Gonalves F, Mendo S, Coimbra MA, Rocha SM.Evaluation of the mutagenicity of sesquiterpenic compounds and theirinfluence on the susceptibility towards antibiotics of two clinically rel-evant bacterial strains. Mutat Res 2011; 723: 1825

15 ztrk M, Duru ME, Kivrak S, Mercan-Doan N, Trkoglu A, zler MA. Invitro antioxidant, anticholinesterase and antimicrobial activity studieson three Agaricus species with fatty acid compositions and iron con-tents: a comparative study on the three most edible mushrooms. FoodChem Toxicol 2011; 49: 13531360

16 Xu X, Yan H, Chen J, Zhang X. Bioactive proteins from mushrooms. Bio-technol Adv 2011; 29: 667674

17 Fuchs FD. Princpios Gerais do Uso de Antimicrobianos. In: Fuchs F,Wannamacher L, Ferreira M, editors. Farmacologia Clnica Funda-mentos da teraputica Racional, 3rd edition. Rio de Janeiro: GuanabaraKoogan; 2004: 342

18 Tenover FC. Mechanisms of antimicrobial resistance in bacteria. AmJ Infect Control 2006; 34 (5 Suppl. 1): S3S10

19 Koch AL. Bacterial wall as target for attack: past, present, and future re-search. Clin Microbiol Rev 2003; 16: 673687

20 Opal SM, Cohen J. Clinical gram-positive sepsis: does it fundamentallydiffer from gram-negative bacterial sepsis? Crit Care Med 1999; 27:16081616

21 Ginsburg I. Role of lipoteichoic acid in infection and inflammation. Lan-cet Infect Dis 2002; 2: 171179

22 Silveira G, Nome F, Gesser JC, S MM, Terenzi H. Estratgias utilizadas nocombate a resistncia bacteriana. Qum Nova 2006; 29: 37

23 Craig WA. Antibacterial therapy. In: Goldman & Ausiell, editor. Ceciltextbook of medicine, 22nd edition. Philadelphia: Saunders; 2004:18531926

24 Harbarth S, Harris AD, Carmeli Y, Samore MH. Parallel analysis of indi-vidual and aggregated data on antibiotic exposure and resistance ingram-negative bacilli. Clin Infect Dis 2001; 33: 14621468

25 Segal-Maurer S, Urban C, Rahal Jr. JJ. Current perspectives on multidru-gresistant bacteria. Epidemiology and control. Infect Dis Clin North Am1996; 10: 939957

26 Kempf M, Rolain JM. Emergence of resistance to carbapenems in Acine-tobacter baumannii in Europe: clinical impact and therapeutic options.Int J Antimicrobiol Agents 2012; 39: 105114

27 WHO.World Health Organization report on infectious diseases 2000 Overcoming antimicrobial resistance. Available at http://www.who.int/infectious-disease-report. Accessed January 21, 2012

28 Peres-Bota D, Rodriguez H, Dimopoulos G, DaRos A, Mlot C, StruelensMJ,Vincent JL. Are infections due to resistant pathogens associated with aworse outcome in critically ill patients? J Infect 2003; 47: 307316

29 Pittet D. Infection control and quality health care in the new millen-nium. Am J Infect Control 2005; 33: 258267

30 WHO. World Health Organization report Antimicrobial resistance(AMR). Available at http://www.who.int/mediacentre/news/releases/2010/amr_20100820/en/index.html. Accessed January 21, 2012

31 Barros L, Cruz T, Baptista P, Estevinho LM, Ferreira ICFR.Wild and com-mercial mushrooms as source of nutrients and nutraceuticals. FoodChem Toxicol 2008; 46: 27422747

32 Ozen T, Darcan C, Aktop O, Turkekul I. Screening of antioxidant, antimi-crobial activities and chemical contents of edible mushrooms wildlygrown in the Black Sea region of Turkey. Comb Chem High ThroughputScreen 2011; 14: 7284

33 Tambekar DH, Sonar TP, Khodke MV, Khante BS. The novel antibacterialsfrom two edible mushrooms: Agaricus bisporus and Pleurotus sajor ca-ju. Int J Pharmacol 2006; 2: 584587

34 Rosa LH, Machado KMG, Jacob CC, Capelari M, Rosa CA, Zani CL. Screen-ing of Brazilian Basidiomycetes for antimicrobial activity. Mem Inst Os-waldo Cruz 2003; 98: 967974

35 Kalyoncu F, Oskay M, Salam H, Erdogan TF, Tamer A. Antimicrobial andantioxidant activities of mycelia of 10 wild mushroom species. J MedFood 2010; 13: 415419species collected from Turkey. Proceeding of the 6th International Con-ference on Mushroom Biology and Mushroom Products, 2008. Krefeld,Germany: J.I. LelleyGAMU GmbH, Institut fr Pilzforschung; 2008

37 Barros L, Venturini BA, Baptista P, Estevinho LM, Ferreira ICFR. Chemicalcomposition and biological properties of Portuguese wild mushrooms:a comprehensive study. J Agric Food Chem 2008; 56: 38563862

38 Solak MH, Kalmis E, Saglam H, Kalyoncu F. Antimicrobial activity of twowild mushrooms Clitocybe alexandri (Gill.) Konr. and Rhizopogon rose-olus (Corda) T.M. Fries collected from Turkey. Phytother Res 2006; 20:10851087

39 Quereshi S, Pandey AK, Sandhu SS. Evaluation of antibacterial activity ofdifferent Ganoderma lucidum extracts. J Sci Res 2010; 3: 913

40 Sheena N, Ajith TA, Mathew AT, Janardhanan KK. Antibacterial activityof three macrofungi, Ganoderma lucidum, Navesporus floccosa andPhellinus rimosus occurring in South India. Pharm Biol 2003; 41: 564567

41 Gao Y, Tang W, Gao H, Chan E, Lan J, Li X, Zhou S. Antimicrobial activityof the medicinal mushroom Ganoderma. Food Rev Int 2005; 21: 211229

42 Smnia A, Monache FD, Smnia EFA, Gil ML, Benchetrit LC, Cruz FS. Anti-bacterial activity of a substance produced by the fungus Pycnoporussanguineus (Fr.) Murr. J Ethnopharmacol 1995; 45: 177181

43 Smnia EFA, Smnia A, Loguercio-Leite C, Gil ML. Optimal parametersfor cinnabarin synthesis by Pycnoporus sanguineus. J Chem Technol Bi-otechnol 1997; 70: 5759

44 Yamac M, Bilgili F. Antimicrobial activities of fruit bodies and/or myce-lial cultures of some mushroom isolates. Pharm Biol 2006; 44: 660667

45 Barros L, Calhelha RC, Vaz JA, Ferreira ICFR, Baptista P, Estevinho LM.Antimicrobial activity and bioactive compounds of Portuguese wildedible mushrooms methanolic extracts. Eur Food Res Technol 2007;225: 151156

46 Barros L, Baptista P, Estevinho LM, Ferreira ICFR. Effect of fruiting bodymaturity stage on chemical composition and antimicrobial activity ofLactarius sp. mushrooms. J Agric Food Chem 2007; 55: 87668771

47 Gezer K, Duru ME, Kivrak I, Turkoglu A, Mercan N, Turkoglu H, Gulcan S.Free-radical scavenging capacity and antimicrobial activity of wild edi-ble mushroom from Turkey. Afr J Biotechnol 2006; 5: 19241928

48 Turkoglu A, Duru ME, Mercan N, Kivrak I, Gezer K. Antioxidant and anti-microbial activities of Laetiporus sulphureus (Bull.) Murrill. Food Chem2007; 101: 267273

49 Dulger B, Ergul CC, Gucin F. Antimicrobial activity of the macrofungusLepista nuda. Fitoterapia 2002; 73: 695697

50 Hearst R, Nelson D, McCollum G, Millar BC, Maeda Y, Goldsmith CE, Roo-ney PJ, Loughrey A, Rao JR, Moore JE. An examination of antibacterialand antifungal properties of constituents of Shiitake (Lentinula edodes)and Oyster (Pleurotus ostreatus) mushrooms. Complement Ther ClinPract 2009; 15: 57

51 Hur JM, Yang CH, Han SH, Lee SH, You YO, Park -C, Kim KJ. Antibacterialeffect of Phellinus linteus against methicillin-resistant Staphylococcusaureus. Fitoterapia 2004; 75: 603605

52 Hatvani N. Antibacterial effect of the culture fluid of Lentinus edodesmycelium grown in submerged liquid culture. Int J Antimicrob Agents2001; 17: 7174

53 Signoretto C, Burlacchini G, Marchi A, Grillenzoni M, Cavalleri G, Ciric L,Lingstrm P, Pezzati E, Daglia M, Zaura E, Pratten J, Spratt DA, Wilson M,Canepari P. Testing a lowmolecular mass fraction of a mushroom (Len-tinus edodes) extract formulated as an oral rinse in a cohort of volun-teers. J Biomed Biotechnol, advance online publication 2011; :DOI:10.1155/2011/857987

54 Hirasawa M, Shouji N, Neta T, Fukushima K, Takada K. Three kinds ofantibacterial substances from Lentinus edodes (Berk.) Sing. (Shiitake,an edible mushroom). Int J Antimicrob Agents 1999; 11: 151157

55 Barros L, Baptista P, Estevinho LM, Ferreira ICFR. Bioactive properties ofthe medicinal mushroom Leucopaxillus giganteus mycelium obtainedin the presence of different nitrogen sources. Food Chem 2007; 105:179186

56 Liu XT, Winkler AL, SchwanWR, Volk TJ, Rott MA, Monte A. Antibacterialcompounds from mushrooms I: a lanostane-type triterpene and pre-nylphenol derivates from Jahnoporus hiritus and Albatrellus flettii andtheir activities against Bacillus cereus and Enterococcus faecalis. PlantaMed 2010; 76: 182185Alves MJ et al. A Review on Planta Med 2012; 78: 17071718

57 Mothana RAA, Jansen R, Jlich WD, Lindequist U. Ganomycins A and B,new antimicrobial Farnesyl hydroquinones from the BasidiomyceteGanoderma pfeifferi. J Nat Prod 2000; 63: 416418

58 Ishikawa NK, Fukushi Y, Yamaji K, Tahara S, Takahashi K. Antimicrobialcuparene-type sesquiterpenes, enokipodins C and D, from a mycelialculture of Flammulina velutipes. J Nat Prod 2001; 64: 932934

59 Bender S, Dumitrache CN, Backhaus J, Christie G, Cross RF, Lonergan GT,Baker WL. A case for caution in assessing the antibiotic activity of ex-tracts of culinary-medicinal Shiitake mushroom [Lentinus edodes(Berk.) Singer] (Agaricomycetideae). Int J Med Mushrooms 2003; 5:3135

60 Quang DN, Bach DD, Hashimoto T, Asakawa Y. Chemical constituents ofthe Vietnamese inedible mushroom Xylaria intracolorata. Nat Prod Res2006; 20: 317321

61 Zheng H, Maoqing Y, Liqiu X, Wenjuan T, Lian L, Guolin Z. Purificationand characterization of an antibacterial protein from the cultured my-celia of Cordyceps sinensis. Wuhan Univ J Nat Sci 2006; 11: 709714

62 Ngai PHK, Ng TB. A ribonuclease with antimicrobial, antimitogenic andantiproliferative activities from the edible mushroom Pleurotus sajor-caju. Peptides 2004; 25: 1117

63 Mygind PH, Fischer RL, Schnorr KM, Hansen MT, Snksen CP, Ludvigsen S,Ravents D, Buskov S, Christensen B, De Maria L, Taboureau O, Yaver D,Elvig-Jrgensen SG, Srensen MV, Christensen BE, Kjrulff S, Frimodt-Moller N, Lehrer RI, Zasloff M, Kristensen HH. Plectasin is a peptide anti-biotic with therapeutic potential from a saprophytic fungu. Nature2005; 437: 975980

64 Lee SJ, Yeo WH, Yun S, Yoo D. Isolation and sequence analysis of newpeptaibol, boletusin, from Boletus spp. J Pept Sci 1999; 5: 374378

65 Yoon SY, Eo SK, Kim YS, Lee CK, Han SS. Antimicrobial activity of Gano-derma lucidum extract alone and in combination with some antibiot-ics. Arch Pharm Res 1994; 17: 438442

66 Anke T, Kupka J, Schramm G, Steglich W. Antibiotics from basidiomy-cetes. X. Scorodonin, a new antibacterial and antifungal metabolitefromMarasmius scorononius (Fr.). J Antibiot 1980; 33: 463467

67 Ciric L, Tymon A, Zaura E, Lingstrm P, Stauder M, Papetti A, Signoretto C,Pratten J, Wilson M, Spratt D. In vitro assessment of Shiitake mushroom(Lentinula edodes) extract for its antigingivitis activity. J Biomed Bio-technol, advance online publication 2011; DOI: 10.1155/2011/507908

68 Signoretto C, Marchi A, Bertoncelli A, Burlacchini G, Tessarolo F, Caola I,Pezzati E, Zaura E, Papetti A, Lingstrm P, Pratten J, Spratt DA, Wilson M,Canepari P. Effects of mushroom and chicory extracts on the physiolo-gy and shape of Prevotella intermedia, a periodontopathogenic bacte-rium. J Biomed Biotechnol, advance online publication 2011; DOI:10.1155/2011/635348

69 SchwanWR, Dunek C, Gebhardt M, Engelbrecht K, Klett T, Monte A, Toce J,Rott M, Volk TJ, LiPuma JJ, Liu XT, McKelvey R. Screening a mushroomextract library for activity against Acinetobacter baumannii and Bur-kholderia cepacia and the identification of a compound with anti-Bur-kholderia activity. Ann Clin Microb Antimicrob 2010; 9: 4

70 Zheng S, Liu Q, Zhang G, Wang H, Ng TB. Purification and characteriza-tion of an antibacterial protein from dried fruiting bodies of the wildmushroom Clitocybe sinopica. Acta Biochim Pol 2010; 51: 4348

71 Nicholas GM, Blunt JW, Munro MHG. Cortamidine oxide, a novel disul-fide metabolite from the New Zealand basidiomycete (mushroom)Cortinarius species. J Nat Prod 2001; 64: 341344

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cap.3, extracte

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