review article host-microbe interactions in caenorhabditis ...pathogens both in the cell-autonomous...

Hindawi Publishing CorporationISRNMicrobiologyVolume 2013 Article ID 356451 7 pageshttpdxdoiorg1011552013356451

Review ArticleHost-Microbe Interactions in Caenorhabditis elegans

Rui Zhang and Aixin Hou

Department of Environmental Sciences School of the Coast and Environment Louisiana State UniversityBaton Rouge LA 70803 USA

Correspondence should be addressed to Aixin Hou ahoulsuedu

Received 18 June 2013 Accepted 16 July 2013

Academic Editors A Hamood and F Navarro-Garcia

Copyright copy 2013 R Zhang and A Hou This is an open access article distributed under the Creative Commons AttributionLicense which permits unrestricted use distribution and reproduction in any medium provided the original work is properlycited

A good understanding of how microbes interact with hosts has a direct bearing on our capability of fighting infectious microbialpathogens and making good use of beneficial ones Among the model organisms used to study reciprocal actions among microbesand hosts C elegans may be the most advantageous in the context of its unique attributes such as the short life cycle easinessof laboratory maintenance and the availability of different genetic mutants This review summarizes the recent advances inunderstanding host-microbe interactions in C elegans Although these investigations have greatly enhanced our understanding ofC elegans-microbe relationships all but one of them involve only one or fewmicrobial species We argue here that more research isneeded for exploring the evolution and establishment of a complexmicrobial community in the wormrsquos intestine and its interactionwith the host

1 Introduction

Host-microbe symbiosis exists in almost all animals andthe symbiotic bacteria can be profitable harmful or of noeffect to the host For example the harmless Escherichiacoli strains commonly found in organismal intestine are anormal part of the gut flora and can advantage their hostsby producing vitamin K [1] and by keeping pathogenicbacteria from colonizing the intestine [2 3] By contrastsome others like E coli strain O26 can cause diseases in itshosts [4] The interactions between host and microbe formcomplicated networks Understanding these interactions canhelp us effectively cure the diseases caused by pathogenicmicrobes and promote good health in animals by benignmicrobes A number of model organisms for example Celegans Saccharomyces cerevisiae Drosophila melanogasterArabidopsis zebrafish andmice have been used to study themechanisms involved in host-microbe interactions Amongthese organisms C elegans has its unique characteristics thatcan be regarded as its advantages being a model animal

The nematode C elegans is a free living multicellularinvertebrate Its two original strains were isolated from soilin France [5] and mushroom compost in England [6] morethan a half-century agoNaturallyC elegans lives onmicrobesincluding bacteria and fungi and it is also a natural host of

some pathogenic microorganisms such as the Gram-negativebacteriumMicrobacterium nematophilum the fungus Drech-meria coniospora the microsporidian parasite Nematocidaparisii and the Orsay virus [7 8] Major attributes of Celegans as a model include its tractability to be easily main-tained in the laboratory the availability of a great number ofgenetic mutants its facility for gene downregulation and theshort life cycle of approximately 2 to 3 weeks C elegans hasbeen used as a model organism since 1965 [9 10] in a broadrange of research areas including RNA interference agingmechanism regulation of fat storage host-pathogen relation-ships pyrimidine biosynthesis pathway [11] apoptosis DNAdamage responses genotoxic stress [12] exploration of usefulfood constituents and drug candidates [13] and identificationof new antioxidant probiotic strains for potential use inhumans [14] We review here various interactions between Celegans and microbes with a focus on the recent findings inunderstanding themechanisms of this host-microbe relation-ship

2 Interactions between Microbial Pathogensand C elegans

Awide variety of bacterial pathogens as well as several fungican kill C elegans or produce nonlethal disease symptoms

2 ISRNMicrobiology

in the worm Notably these microbes include some well-known human pathogens such as Gram-negative bacteriaof genera Burkholderia Pseudomonas Salmonella Serratiaand Yersinia Gram-positive bacteria Enterococcus Staphy-lococcus and Streptococcus and the fungus Cryptococcusneoformans Next we summarize the mechanisms involvedin the interplay of C elegans with its microbial pathogens

21 Tactics Pathogens Apply to Injure C elegans Usuallymicrobial pathogens colonize the C elegans intestine anddecrease its lifespan Some of them adhere to the nematodecuticle while others produce toxins that kill C elegans with-out a need for the live bacterial cells to directly contact withthe worm [15] The following (presented chronologically) aresome examples of major tactics that pathogenic microbesapply to injure C elegans

(i) Salmonella enterica serovar Typhimurium is found tobe virulent in C elegans through modulation of itsvirulence by DNA adenine methyltransferase (DAM)[16]

(ii) A coryneform bacterium named Microbacteriumnematophilum can colonize the rectum of infectedworms and cause localized swelling coprostasis andretardant growth [17]

(iii) Listeria monocytogenes can infect C elegans extracel-lularly leading to its death by bacterial accumulationin the worm intestine [18]

(iv) Direct interaction between live nontyphoidal salmo-nellae (NTS) a bacterium that causes gastroenteritisworldwide and C elegans is necessary for the wormrsquoslethality [19]

(v) Yersinia enterocolitica strains can kill C elegans andthe tcaA gene that encodes an insecticidal toxin playsa great role in the nematocidal activity [20]

(vi) In soil in order to prevent themselves from beingpredated by bacterivorous nematodes many bacteriahave evolved defense mechanisms such as releasingtoxic molecules For example the extracellular sec-ondary metabolites that are produced by the modelsoil bacterium Pseudomonas fluorescens function asa defense strategy against bacterivorous nematodes[21]

(vii) Cronobacter sakazakii a human pathogen can infectC elegans at an infection rate that depends on thebacterial accumulation inside the host and induce theantimicrobial genes in C elegans [22]

(viii) Shigella flexneri the causative agent of bacillary dys-entery can kill C elegans The bacterial virulencegenes and the candidate antimicrobial genes of thehost are kinetically regulated in C elegans duringinfection [23]

(ix) Bacterial mucoid strains synthesize exopolysaccha-ride matrix to avoid the induction of NPR-1-depend-ent behaviors ofC elegans so as to inhibit specific hostresponses to microbes [24]

(x) The yeast form of Candida albicans can cause anintestinal infection in C elegans whereas heat-killedyeast is innocuous This indicates that the hostresponse to C albicans is largely mediated by patternrecognition that is pathogen-associated molecularpatterns or PAMPs which are a group of conservedmicrobial molecules Also it has been found that inresponse to fungal pathogens C elegans selectivelyrepresses the transcription of antibacterial immuneeffectors That is to say nematodes selectively mountspecific antifungal defenses at the expense of antibac-terial responses [25]

(xi) Different strains of Burkholderia pseudomallei thecausative agent ofmelioidosis that can cause consider-able damage in animals have diverse ability to kill Celegans Its virulence depends on a junction of geneticand environmental factors C elegans requires pro-liferating B pseudomallei to consecutively producetoxins to regulate thorough killing [26]

(xii) Vibrio cholerae cytolysin (VCC) is reported as amajorvirulence factor which invokes multifarious immuneresponse related genes during V cholerae infection inC elegans [27]

(xiii) Three lactic bacteria strains Lactobacillus salivar-ius Lactobacillus reuteri and Pediococcus acidilacticihave been found to hinder the wormrsquos developmentand growth obstruct the germ cells growth andinduce the gene expressions involved in pathogenresponse [28]

Additionally it is worth noting that the virulence ofmicrobes can be impacted by preinfection of C elegans withother pathogens For instance preinfection with pathogenStaphylococcus aureus increases the vulnerability of the Celegans host by perverting its immune system which thenallows the opportunistic pathogen Proteus mirabilis to bepathogenic to this host [29] Also pore-forming toxins (PFTs)are important bacterial virulence factors and essential forthe pathogenesis of many Gram-positive and Gram-negativebacteria They act by poking holes in the plasma membraneof cells Besides horizontal gene transfer (HGT) betweenbacteria occurs in the intestinal tract of their animal hosts andfacilitates both virulence and antibiotic resistance [30] Last ithas been discovered that Orsay virus can infectC elegans andcause abnormal morphologies of C elegans intestinal cellsthemechanismunderneath this type of infection has not beenrevealed yet [7]

22 Tactics Employed by C elegans to Battle against PathogensA number of strategies are known to be used by C elegans tobattle against pathogens First C elegans owns mechanismsto avoid certain pathogens For example C elegans specif-ically avoids some strains of Serratia appertaining to theirproduction of the cyclic lipodepsipentapeptide serrawettinW2 This voidance behavior requires G protein signalingpathways and the sole C elegans Toll-like receptor TOL-1 [31] The hypothesis is further supported by the findingthat pathogen recognition through Toll-like receptors (TLRs)

ISRNMicrobiology 3

is crucial for C elegans to launch an appropriate immuneresponse against microorganisms A study [32] has observedthat the tol-1 mutated C elegans can be killed by the humanpathogen Salmonella enterica by causing a marked pharyn-geal invasion It also has reported that TOL-1 in C elegansis required for the normal expression of two pharyngeal-expressed genes a defensing like molecule ABF-2 and aheat-shock protein 1641 which is essential for C elegansimmunity These findings confirm that TOL-1 has a directeffect on defense response of C elegans to some pathogenicmicrobes Another bolstering example is that C eleganscan avoid cultures and culture supernatants of pathogenicbacterium Staphylococcus aureus by recognizing secretorymolecules including toxic shock syndrome toxin 1 (TSST-1)and staphylococcal enterotoxin C (SEC) This avoidance isfound to be dependent on Tollinterleukin-1 receptor (TIR-1) and generation of 5-hydroxytryptamine (5-HT) [33] Thediscovery substantiates the finding that the immune responseto pathogenic or nutritional bacteria in C elegans needs asignaling pathway that contains the mammalian orthologsof Toll-interleukin-1 receptor (TIR) domain protein sterile 120572and TIRmotif (SARM) themitogen-activated protein kinasekinase kinase (MAPKKK) apoptosis signal-regulating kinase1 (ASK1) and the mitogen-activated protein kinase kinase(MAPKK) MKK3 which activates p38 MAPK The SARM-ASK1-MKK3 pathway functions in C elegans in response topathogens both in the cell-autonomous regulation of innateimmunity and the neuroendocrine regulation of serotonin-dependent aversive behavior [34] Aside from the previousmechanisms C elegans can adjust its olfactory preferencesafter exposure to pathogenic bacteria avoiding odors fromthe pathogens and increasing its attraction to odors fromfamiliar nonpathogenic bacteria [35]

Next the C elegans transcription factor SKN-1 whichregulates oxidative and xenobiotic stress response and profitslongevity is found to be necessary for pathogen resistanceto both Gram-negative Pseudomonas aeruginosa and Gram-positive Enterococcus faecalis Both the Toll-interleukin 1receptor (TIR) domain containing adaptor protein TIR-1 andthe p38 mitogen-activated protein kinase (MAPK) orthologPMK-1 are needed in the SKN-1 stimulation byPA14 exposure[36] Moreover it has been observed that development of Celegans larvae on pathogens results in enhanced resistance todifferent pathogens and to heat shockThe boosted pathogenresistance may be attributed to the early initiation of theheat shock response in the worms and the resultant lifespanincrease can be related to the DBL-1 transforming growthfactor 120573-like (TGF120573-like) DAF-2DAF-16 insulin-like andp38 MAP kinase pathways [37] Also c-Jun N-terminalkinase (JNK)-like MAPK but not p38 MAPK pathway isfound as a key regulator of transcriptionally-induced pore-forming toxins (PFT) defenses and the activator protein AP-1 a downstream target of the JNK-mediated PFT protec-tion pathway is uncovered as one of the cellular compo-nents important for protecting C elegans against pathogen-produced PFTs [38]

In addition C elegans is capable of reducing the toxicityof various small molecule toxins produced by pathogensby chemically modifying O-N-glycosylation and unusual

31015840-O-phosphorylation of the resultant glucosides [39] Thecharacteristic antibiotic constituents such as antimicrobialpeptides (AMPs) in C elegans are essential to protect theworm against infection The majority of AMPs in C elegansare caenopores and they kill bacteria by permeabilizingtheir cytoplasmic membrane and executing pore-formingactivityTheAMPs are also required to tackle with the regularbacterial food of C elegans Escherichia coli and withoutthemC elegans grows poorly with a great number of bacteriaaccumulated in the wormrsquos intestine Therefore the caeno-pore class of AMP may be an important factor in enablingC elegans to live with microbes [40] Some AMP genesare induced upon contact with particular bacteria whereasothers are stimulated regardless of the bacteria they feed onN-glycans are also found to play a role in the interaction of Celegans with pathogenic bacteria indicating that N-glycansare components of the wormrsquos innate immune system [41]Lysozymes are antimicrobial enzymes that play a pressing rolein resisting infection in a wide scope of eukaryotes Deletionof the protist type lysozyme LYS-7 can make C eleganssusceptible to killing by fungus Cryptococcus neoformansa fatal human pathogen but enhance its tolerance to theenteric bacteria Salmonella Typhimurium These compoundresponses indicate higher levels of complexity in the Celegans innate immune system [42]C elegans can respond topathogens by generating reactive oxygen species (ROS) in theintestine while synchronically instigating an oxidative stressresponse which is dependent on transcriptional regulatorDAF-16 to protect adjacent tissues [43]

Besides it has been discovered that C elegans hete-rochromatin protein HPL-1 interacts with the linker histonevariant HIS-24monomethylated at lysine 14 (HIS-24K14me1)and associates with promoters of the genes involved inthe wormrsquos antimicrobial response suggesting a functionalpartnership between epigenetic regulation and the innateimmune system in C elegans [44] Natural variation in theC elegans resistance to pathogen infection has proven to becaused by a polymorphism in the NPR-1 gene which encodesa mammalian neuropeptide Y receptor homolog The NPR-1-mediated pathogen resistance mechanism however is viaoxygen-dependent behavioral avoidance instead of directregulation of innate immunity [45] Another antimicrobialmechanism in C elegans is the wormrsquos antiviral RNA inter-ference machinery which has been discovered to function indealingwith the replication of the artificially introducedFlockhouse virus (FHV) and Orsay virus infection in C elegans[7 46]

The interaction between microbial pathogens and Celegans is a relatively new research topic It is likely that apartfrom the previous means other mechanisms of interactionbetween the pathogens and the worm have yet to be discov-ered In particular more research is needed to determine thecomplex interplay among different mechanisms

3 Interactions between Commensal Microbesand C elegans

31 Bacteria Are the Food Source of C elegans In the naturalcondition C elegans often encounters many different types

4 ISRNMicrobiology

of materials and it uses mechanoreceptor neurons (MRNs)to recognize collisions with particles and detect bacteriaHermaphrodites and males possess 22 putative MRNs malespossess another 46 MRNs most if not all of which areneeded for mating [47] In the process of touch sensationa mechanical stimulus is converted into electrical signalsthrough the activation of ion channels that respond tomechanical stimuli [48] Serotonin an endogenous pharyn-geal pumping activator whose action is triggered by bacteriaactivates pharyngeal pumping and isthmus peristalsis (bothare required motions in the process of C elegansrsquo feeding) byactivating two separate neural pathways [49ndash51] For activat-ing pumping the SER-7 serotonin receptor in the MCmotorneurons in the feeding organ activates cholinergic transmis-sion from MC to the pharyngeal muscles by triggering theGs alpha signaling pathway For activating isthmus peristalsisthe SER-7 in the M4 (and possibly M2) motor neuron in thefeeding organ stimulates the G(12)alpha signaling pathway ina cell-autonomous manner which probably initiates neuro-transmission fromM4 to the pharyngeal muscles [52] Somesoil bacteria are commensal but others may be pathogenicC elegans is attracted to nutritious bacteria and is repelledby pathogens and toxins using mechanisms previously dis-cussed C elegans discriminates food both physically basedon size and chemically based on taste and olfaction [53]Interestingly depending on its experience C elegans canalso differentiate beneficial bacteria from toxic bacteria byincreasingly releasing the neurotransmitter serotonin ontointerneurons [54] C elegans has evolved diverse actions forseeking high quality food and leaving low quality bacteriaThis food-searching performance is enhanced in the wormsthat have already experienced good food When searchingfor good food worms switch between two motion modesdwelling which is a kind of movement with recurrent ceasesand turns which is common when animals are on good foodand roaming which is a type of unswerving fast movementwhich usually happens when worms are on bad food AIYneuron has been found serving to extend roaming terms andit is capital for seeking effective food [55]

32 Bacterial Strain Affects the Life Span of C elegans Twostrains ofBacillus mycoides andBacillus soli have been singledout as C elegansrsquo preferred food compared to strain E coliOP50 a common food used for the worm at laboratory andboth can extend the life span of C elegans by activatingthe autophagic process [56] Lactobacillus rhamnosus CNCMI-3690 also can lengthen the wormrsquos life expectancy andinduce different expression of the DAF-16insulin-like path-way which is greatly conserved in humans Importantly thismay suggest that C elegans can probably be used to identifynew potential antioxidant probiotic strains for future use inhumans [14] Also it has been observed that food limitationcan increase the lifespan of C elegans [57] Additionally asworms age bacteria accumulate in the intestinal tract [58]and C elegansrsquo intestinal bacterial accumulation which isregulated by intestinal immunity is one of the importantlifespan determinants (other factors are bacterial strainworm genotype and biologic age) [59]

33 Interspecies Signaling Occurs between C elegans and Mi-crobes Bacterially derived nitric oxide (NO) produced fromthe natural food of C elegans Bacilli that contain functionalNO synthase is an essential signaling molecule in multicel-lular organismsThis compound elevatesC elegansrsquo longevityand stresses resistance through a class of genes that act underthe paired control of HSF-1 and DAF-16 transcription factors[60] Moreover a recent study reports that two Escherichiacoli endogenous noncoding RNAs OxyS and DsrA affectC elegans physiology OxyS down regulates che-2 leadingto C elegans chemosensory behavior impairment and DsrAinhibits diacylglycerol lipase gene F42G96 giving rise toa longevity decrease The study indicates that noncodingRNAs might have interspecies ecological roles [61] Anotherstudy [62] finds that bacterial strain affects the fat storage ofC elegans through interspecies signaling The authors havereported that nutrient differences of fatty acid compositionand carbohydrate levels in different E coli strains werenot found to have a causative effect on fat storage levelsin the worms instead specific peptides or amino acidsmay have provided nutritional signals regulating fat storagelevels

34 C elegansrsquo Behavioral State Varies in Response to BacterialSupplies Food quantity and quality can modulate C elegansrsquobehavioral stages If worms are given sufficient high-qualityfood they will finally become saturated and stagnant andstop eating and moving [63] If the first larval stage (L1)worms are starved they can choose to enter into dauer stagein which C elegans becomes thin dense and motionlessunless disturbed probably for reserving energy Dauer lar-vae usually gather together into a droplet of condensationAnother dauer-specific behavior is nictation in which thelarva sets a projection and jumps up on its tail swaying itshead in the air [64]This would possibly allow the dauer larvato adhere to passing organisms to be transferred itself to anew environment or to search for food source Dauer larvaecan survive several months without food After the food isprovided again they can bypass the larval stages 2 (L2) and 3(L3) and get into the fourth larval stage (L4) directly [65]

4 Interactions between Host and IntestinalMicrobiota in C elegans

As far as we are aware all the investigations on host-microbein C elegans had dealt with only one or few bacterialspecies till the present year In 2013 Shapirarsquos researchgroup first characterized the C elegans natural gut microbialcommunities by growing germ-free worms in a natural-mimic environment of soil and rotting fruit with 18 specieshaving been identified These species include Bacillus spBacillusmegateriumBacillus spBacillus aryabhattaiBacillusthuringiensis Bacillus foraminisBacillus asahii BacillusnealsoniiBacillus circulans Bacillus subtilis PaenibacillusspPaenibacillus lautusPaenibacillus odorifer LysinibacillusfusiformisLysinibacillus xylanilyticusLysinibacillus sphaeri-cus Staphylococcus warneriStaphylococcus pasteuri Bacillus

ISRNMicrobiology 5

spBacillus pumilus Pseudomonas spPseudomonas oleovor-ansPseudomonas stutzeriP mendocinaPseudomonas pseu-doalcaligenes P aeruginosaP mendocinaPseudomonas alcal-igenes P oleovoransP mendocinaP pseudoalcaligenes Pseu-domonas trivialisPseudomonas poae Pseudomonas fluores-censPseudomonas moraviensisPseudomonas koreensisPseu-domonas putida Arthrobacter sp Enterobacter spPasteur-ella aerogenes Rahnella aquatilis and Buttiauxella agres-tisButtiauxella noackiae They discovered that members ofC elegans microbiota can enhance the hostrsquos pathogenicresistance although disparate components may employ dis-tinct resistance mechanisms For the two primary speciesof the identified bacteria Bacillus megaterium (BM) andPseudomonas mendocina (PM) the increase in hostrsquos infec-tion resistance supplied by BM is related to the compromisedreproduction while the protection provided by PM is repro-duction-independent by activating the p38-dependent path-way to prime the worm immune system Considering thep38 pathway is one of the functionally conserved signalingpathways throughout the animal kingdom this disclosuremay indicate that similar interactions might also be presentin mammals [66]

5 Outlook

It has beenwell recognized thatmammals including humanshave highly complex microbiota in their intestines thatcontributes to gut maturation host nutrition and pathogenresistance as well as regulate host energy metabolism andinflammatory immune responses Therefore a good under-standing of intestinal microbial ecology allows us to bettermanage and promote human health Due to the difficulty ofusing human subjects as models in experiments mice havebeen commonly used in the ecological study of mammalintestinal microbial communities however the generationinterval of mice is long and it is more difficult and costlyto handle the animal Given the advantages of C elegans as amodel animal and importantly the lower costs associatedwithC elegans experiments an interesting question to ask is thefollowing can studying the host-microbiota interactions inC elegans confer insights into the counterparts in mammalsAt the moment there is no clear answer to it

C elegans has been widely used as a model to investigateanimal development and behavior but the research oninteraction between microbe and C elegans is still relativelynew Recent investigations have greatly enhanced our under-standing of C elegans-microbe relationships but all exceptone involve only one or few microbial species More researchis needed to examine for instance how a complex microbialcommunity may evolve and be established in the wormrsquosintestine and how this microbiota interacts with the hostbefore we can confidently answer the previous question

References

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[2] S Hudault J Guignot and A L Servin ldquoEscherichia colistrains colonising the gastrointestinal tract protect germfreemice against Salmonella typhimurium infectionrdquo Gut vol 49no 1 pp 47ndash55 2001

[3] G Reid J Howard and B S Gan ldquoCan bacterial interferenceprevent infectionrdquoTrends inMicrobiology vol 9 no 9 pp 424ndash428 2001

[4] C Sekse M Sunde B-A Lindstedt et al ldquoPotentially human-pathogenic Escherichia coli O26 in Norwegian sheep flocksrdquoApplied and Environmental Microbiology vol 77 no 14 pp4949ndash4958 2011

[5] V Nigon ldquoLes modalites de la reproduction et le determinismedu sexe chez quelques nematodes libresrdquo Annales des SciencesNaturelles Zoologie et Biologie Animale vol 11 no 2 pp 1ndash1321949

[6] W L Nicholas E C Dougherty and E L Hansen ldquoAxeniccultivation of caenorharditis briggsae (nematoda rhabditidae)with chemically undefined supplements comparative studieswith related nematodesrdquo Annals of the New York Academy ofSciences vol 77 no 2 pp 218ndash236 1959

[7] M A Felix A Ashe J Piffaretti et al ldquoNatural and experi-mental infection of Caenorhabditis nematodes by novel virusesrelated to nodavirusesrdquo PLOS Biology vol 9 no 1 Article IDe1000586 2011

[8] E K Marsh and R C May ldquoCaenorhabditis elegans a modelorganism for investigating immunityrdquoApplied and Environmen-tal Microbiology vol 78 no 7 pp 2075ndash2081 2012

[9] S Brenner ldquoThe genetics of behaviourrdquo BritishMedical Bulletinvol 29 no 3 pp 269ndash271 1973

[10] W BWoodTheNematode Caenorhabditis Elegans Cold SpringHarbor Monograph Series Cold Spring Harbor LaboratoryNew York NY USA 1988

[11] S Kim D-H Park T H Kim M Hwang and J ShimldquoFunctional analysis of pyrimidine biosynthesis enzymes usingthe anticancer drug 5-fluorouracil in Caenorhabditis elegansrdquoThe FEBS Journal vol 276 no 17 pp 4715ndash4726 2009

[12] L V Scholer T H Moller S Noslashrgaard L Vestergaard and AOlsen ldquoIsolating genes involved with genotoxic drug responsein the nematode Caenorhabditis elegans using genome-wideRNAi screeningrdquoMethods inMolecular Biology vol 920 pp 27ndash38 2012

[13] N Kashima Y Fujikura T Komura et al ldquoDevelopment of amethod for oral administration of hydrophobic substances toCaenorhabditis elegans pro-longevity effects of oral supplemen-tation with lipid-soluble antioxidantsrdquo Biogerontology vol 13pp 337ndash344 2012

[14] G Grompone P Martorell S Llopis et al ldquoAnti-inflammatoryLactobacillus rhamnosus CNCM I-3690 strain protects againstoxidative stress and increases lifespan in Caenorhabditis ele-gansrdquo PLoS One vol 7 no 12 Article ID e52493 2012

[15] C Darby ldquoInteractions with microbial pathogensrdquoWormBookpp 1ndash15 2005

[16] J P Oza J B Yeh and N O Reich ldquoDNA methylationmodulates Salmonella enterica serovar Typhimurium virulencein Caenorhabditis elegansrdquo FEMSMicrobiology Letters vol 245no 1 pp 53ndash59 2005

[17] T Akimkina K Yook S Curnock and J Hodgkin ldquoGenomecharacterization analysis of virulence and transformation ofMicrobacterium nematophilum a coryneform pathogen of thenematode Caenorhabditis elegansrdquo FEMS Microbiology Lettersvol 264 no 2 pp 145ndash151 2006

6 ISRNMicrobiology

[18] L E Thomsen S S Slutz M-W Tan and H Ingmer ldquoCaen-orhabditis elegans is a model host for Listeria monocytogenesrdquoApplied and Environmental Microbiology vol 72 no 2 pp1700ndash1701 2006

[19] M V Jesudason V Balaji and S Densibai ldquoToxigenicity testingof clinical isolates of non-typhoidal salmonellae in Vero cellculture amp Caenorhabditis elegans modelrdquo Indian Journal ofMedical Research vol 123 no 6 pp 821ndash824 2006

[20] B Spanier M Starke F Higel S Scherer and T M FuchsldquoYersinia enterocolitica Infection and tcaA-dependent killing ofcaenorhabditis elesansrdquo Applied and Environmental Microbiol-ogy vol 76 no 18 pp 6277ndash6285 2010

[21] N Neidig R J Paul S Scheu and A Jousset ldquoSecondarymetabolites of pseudomonas fluorescens CHA0 drive com-plex non-trophic interactions with bacterivorous nematodesrdquoMicrobial Ecology vol 61 no 4 pp 853ndash859 2011

[22] B S Sivamaruthi A Ganguli M Kumar S Bhaviya S KPandian and K Balamurugan ldquoCaenorhabditis elegans as amodel for studying Cronobacter sakazakii ATCC BAA-894pathogenesisrdquo Journal of Basic Microbiology vol 51 no 5 pp540ndash549 2011

[23] P Kesika S Karutha Pandian and K Balamurugan ldquoAnalysisof Shigella flexneri-mediated infections in model organismCaenorhabditis elegansrdquo Scandinavian Journal of Infectious Dis-eases vol 43 no 4 pp 286ndash295 2011

[24] K C Reddy R C Hunter N Bhatla D K Newman and DH Kim ldquoCaenorhabditis elegansNPR-1-mediated behaviors aresuppressed in the presence of mucoid bacteriardquo Proceedings ofthe National Academy of Sciences of the United States of Americavol 108 no 31 pp 12887ndash12892 2011

[25] R Pukkila-Worley F M Ausubel and E Mylonakis ldquoCandidaalbicans infection of Caenorhabditis elegans induces antifungalimmune defensesrdquo PLoS Pathogens vol 7 no 6 Article IDe1002074 2011

[26] S-H Lee S-K Ooi N M Mahadi M-W Tan and S NathanldquoComplete killing of Caenorhabditis elegans by Burkholderiapseudomallei is dependent on prolonged direct associationwiththe viable pathogenrdquo PLoS One vol 6 no 3 Article ID e167072011

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[28] M K Fasseas C Fasseas K C Mountzouris and P SyntichakildquoEffects of Lactobacillus salivarius Lactobacillus reuteri andPediococcus acidilactici on the nematode Caenorhabditis ele-gans include possible antitumor activityrdquo Applied Microbiologyand Biotechnology vol 97 no 5 pp 2109ndash2118 2013

[29] G JebaMercy and K Balamurugan ldquoEffects of sequentialinfections ofCaenorhabditis eleganswith Staphylococcus aureusand Proteus mirabilisrdquo Microbiology and Immunology vol 56no 12 pp 825ndash835 2012

[30] C Portal-Celhay K Nehrke and M J Blaser ldquoEffect of Caen-orhabditis elegans age and genotype on horizontal gene transferin intestinal bacteriardquoTheFASEB Journal vol 27 no 2 pp 760ndash768 2013

[31] E Pradel Y Zhang N Pujol T Matsuyama C I Bargmannand J J Ewbank ldquoDetection and avoidance of a naturalproduct from the pathogenic bacterium Serratia marcescens byCaenorhabditis elegansrdquo Proceedings of the National Academy ofSciences of the United States of America vol 104 no 7 pp 2295ndash2300 2007

[32] J L Tenor and A Aballay ldquoA conserved Toll-like receptor isrequired for Caenorhabditis elegans innate immunityrdquo EMBOReports vol 9 no 1 pp 103ndash109 2008

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[34] R P Shivers T Kooistra S W Chu D J Pagano and D HKim ldquoTissue-specific activities of an immune signaling moduleregulate physiological responses to pathogenic and nutritionalbacteria in C elegansrdquo Cell Host and Microbe vol 6 no 4 pp321ndash330 2009

[35] Y Zhang H Lu and C I Bargmann ldquoPathogenic bacteriainduce aversive olfactory learning in Caenorhabditis elegansrdquoNature vol 438 no 7065 pp 179ndash184 2005

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[38] C Y Kao F C Los D L Huffman et al ldquoGlobal functionalanalyses of cellular responses to pore-forming toxinsrdquo PLOSPathogens vol 7 no 3 Article ID e1001314 2011

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[40] T Roeder M Stanisak C Gelhaus I Bruchhaus J Grotzingerand M Leippe ldquoCaenopores are antimicrobial peptides in thenematode Caenorhabditis elegans instrumental in nutrition andimmunityrdquo Developmental and Comparative Immunology vol34 no 2 pp 203ndash209 2010

[41] H Shi J Tan and H Schachter ldquoN-Glycans are involved inthe response of Caenorhabditis elegans to bacterial pathogensrdquoMethods in Enzymology vol 417 pp 359ndash389 2006

[42] E K Marsh M C W van den Berg and R C May ldquoA Two-Gene balance regulates salmonella typhimurium tolerance inthe nematode Caenorhabditis elegansrdquo PLoS One vol 6 no 3Article ID e16839 2011

[43] V Chavez A Mohri-Shiomi A Maadani L A Vega and DA Garsin ldquoOxidative stress enzymes are required for DAF-16-mediated immunity due to generation of reactive oxygenspecies by Caenorhabditis elegansrdquo Genetics vol 176 no 3 pp1567ndash1577 2007

[44] M Studencka A Konzer G Moneron et al ldquoNovel roles ofCaenorhabditis elegans heterochromatin proteinHP1 and linkerhistone in the regulation of innate immune gene expressionrdquoMolecular and Cellular Biology vol 32 no 2 pp 251ndash265 2012

[45] K C Reddy E C Andersen L Kruglyak and D H Kim ldquoApolymorphism in npr-1 is a behavioral determinant of pathogensusceptibility in C elegansrdquo Science vol 323 no 5912 pp 382ndash384 2009

[46] R Lu M Maduro F Li et al ldquoAnimal virus replication andRNAi-mediated antiviral silencing in Caenorhabditis elegansrdquoNature vol 436 no 7053 pp 1040ndash1043 2005

[47] M B Goodman ldquoMechanosensationrdquo WormBook pp 1ndash142006

[48] L Bianchi ldquoMechanotransduction touch and feel at the molec-ular level as modeled in Caenorhabditis elegansrdquo MolecularNeurobiology vol 36 no 3 pp 254ndash271 2007

ISRNMicrobiology 7

[49] N A Croll andM S James ldquoIntegrated behavior in the feedingphase ofCaenorhabditis elegansrdquo Journal of Zoology vol 184 pp507ndash517 1978

[50] H R Horvitz M Chalfie and C Trent ldquoSerotonin and octo-pamine in the nematode Caenorhabditis elegansrdquo Science vol216 no 4549 pp 1012ndash1014 1982

[51] J-T A ChiangM Steciuk B Shtonda and L Avery ldquoEvolutionof pharyngeal behaviors and neuronal functions in free-livingsoil nematodesrdquo Journal of Experimental Biology vol 209 no10 pp 1859ndash1873 2006

[52] B-M Song and L Avery ldquoSerotonin activates overall feedingby activating two separate neural pathways in Caenorhabditiselegansrdquo Journal of Neuroscience vol 32 no 6 pp 1920ndash19312012

[53] Y Kiyama K Miyahara and Y Ohshima ldquoActive uptake ofartificial particles in the nematode Caenorhabditis elegansrdquoJournal of Experimental Biology vol 215 no 7 pp 1178ndash11832012

[54] C H Rankin ldquoNematode behavior the taste of success thesmell of dangerrdquo Current Biology vol 16 no 3 pp R89ndashR912006

[55] B B Shtonda and L Avery ldquoDietary choice behavior inCaenorhabditis elegansrdquo Journal of Experimental Biology vol209 no 1 pp 89ndash102 2006

[56] E A-E Abada H Sung M Dwivedi B-J Park S-K Lee andJ Ahnn ldquoC elegans behavior of preference choice on bacterialfoodrdquoMolecules and Cells vol 28 no 3 pp 209ndash213 2009

[57] S So T Tokumaru K Miyahara and Y Ohshima ldquoControl oflifespan by food bacteria nutrient limitation and pathogenicityof food in C elegansrdquo Mechanisms of Ageing and Developmentvol 132 no 4 pp 210ndash212 2011

[58] D Garigan A-L Hsu A G Fraser R S Kamath J Abringetand C Kenyon ldquoGenetic analysis of tissue aging in Caenorhab-ditis elegans a role for heat-shock factor and bacterial prolifer-ationrdquo Genetics vol 161 no 3 pp 1101ndash1112 2002

[59] C Portal-Celhay E R Bradley and M J Blaser ldquoControl ofintestinal bacterial proliferation in regulation of lifespan inCaenorhabditis elegansrdquo BMC Microbiology vol 12 article 492012

[60] I Gusarov L Gautier O Smolentseva et al ldquoBacterial nitricoxide extends the lifespan of C elegansrdquo Cell vol 152 no 4 pp818ndash830 2013

[61] H Liu X Wang H Wang et al ldquoEscherichia coli noncodingRNAs can affect gene expression and physiology of Caenorhab-ditis elegansrdquo Nature Communications vol 3 article 1073 2012

[62] K K Brooks B Liang and J L Watts ldquoThe influence ofbacterial diet on fat storage in C elegansrdquo PLoS One vol 4 no10 Article ID e7545 2009

[63] L Avery andY-J You ldquoC elegans feedingrdquoWormBook pp 1ndash232012

[64] N A Croll and B E Matthews Biology of Nematodes JohnWiley amp Sons New York NY USA 1977

[65] D L Riddle C Elegans II Cold Spring Harbor LaboratoryPress Plainview NY USA 1997

[66] S Montalvo-Katz H Huang M David Appel M Berg andM Shapira ldquoAssociation with soil bacteria enhances p38-dependent infection resistance in Caenorhabditis eleganrdquo Infec-tion and Immunity vol 81 no 2 pp 514ndash520 2013

Submit your manuscripts athttpwwwhindawicom

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Anatomy Research International

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International Journal of

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Zoology


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BioinformaticsAdvances in

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Evolutionary BiologyInternational Journal of



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ArchaeaHindawi Publishing Corporationhttpwwwhindawicom Volume 2014


Genetics Research International


Advances in

Virolog y

Hindawi Publishing Corporationhttpwwwhindawicom

Nucleic AcidsJournal of

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Stem CellsInternational



Enzyme Research



Microbiology

2 ISRNMicrobiology

in the worm Notably these microbes include some well-known human pathogens such as Gram-negative bacteriaof genera Burkholderia Pseudomonas Salmonella Serratiaand Yersinia Gram-positive bacteria Enterococcus Staphy-lococcus and Streptococcus and the fungus Cryptococcusneoformans Next we summarize the mechanisms involvedin the interplay of C elegans with its microbial pathogens

21 Tactics Pathogens Apply to Injure C elegans Usuallymicrobial pathogens colonize the C elegans intestine anddecrease its lifespan Some of them adhere to the nematodecuticle while others produce toxins that kill C elegans with-out a need for the live bacterial cells to directly contact withthe worm [15] The following (presented chronologically) aresome examples of major tactics that pathogenic microbesapply to injure C elegans

(i) Salmonella enterica serovar Typhimurium is found tobe virulent in C elegans through modulation of itsvirulence by DNA adenine methyltransferase (DAM)[16]

(ii) A coryneform bacterium named Microbacteriumnematophilum can colonize the rectum of infectedworms and cause localized swelling coprostasis andretardant growth [17]

(iii) Listeria monocytogenes can infect C elegans extracel-lularly leading to its death by bacterial accumulationin the worm intestine [18]

(iv) Direct interaction between live nontyphoidal salmo-nellae (NTS) a bacterium that causes gastroenteritisworldwide and C elegans is necessary for the wormrsquoslethality [19]

(v) Yersinia enterocolitica strains can kill C elegans andthe tcaA gene that encodes an insecticidal toxin playsa great role in the nematocidal activity [20]

(vi) In soil in order to prevent themselves from beingpredated by bacterivorous nematodes many bacteriahave evolved defense mechanisms such as releasingtoxic molecules For example the extracellular sec-ondary metabolites that are produced by the modelsoil bacterium Pseudomonas fluorescens function asa defense strategy against bacterivorous nematodes[21]

(vii) Cronobacter sakazakii a human pathogen can infectC elegans at an infection rate that depends on thebacterial accumulation inside the host and induce theantimicrobial genes in C elegans [22]

(viii) Shigella flexneri the causative agent of bacillary dys-entery can kill C elegans The bacterial virulencegenes and the candidate antimicrobial genes of thehost are kinetically regulated in C elegans duringinfection [23]

(ix) Bacterial mucoid strains synthesize exopolysaccha-ride matrix to avoid the induction of NPR-1-depend-ent behaviors ofC elegans so as to inhibit specific hostresponses to microbes [24]

(x) The yeast form of Candida albicans can cause anintestinal infection in C elegans whereas heat-killedyeast is innocuous This indicates that the hostresponse to C albicans is largely mediated by patternrecognition that is pathogen-associated molecularpatterns or PAMPs which are a group of conservedmicrobial molecules Also it has been found that inresponse to fungal pathogens C elegans selectivelyrepresses the transcription of antibacterial immuneeffectors That is to say nematodes selectively mountspecific antifungal defenses at the expense of antibac-terial responses [25]

(xi) Different strains of Burkholderia pseudomallei thecausative agent ofmelioidosis that can cause consider-able damage in animals have diverse ability to kill Celegans Its virulence depends on a junction of geneticand environmental factors C elegans requires pro-liferating B pseudomallei to consecutively producetoxins to regulate thorough killing [26]

(xii) Vibrio cholerae cytolysin (VCC) is reported as amajorvirulence factor which invokes multifarious immuneresponse related genes during V cholerae infection inC elegans [27]

(xiii) Three lactic bacteria strains Lactobacillus salivar-ius Lactobacillus reuteri and Pediococcus acidilacticihave been found to hinder the wormrsquos developmentand growth obstruct the germ cells growth andinduce the gene expressions involved in pathogenresponse [28]

Additionally it is worth noting that the virulence ofmicrobes can be impacted by preinfection of C elegans withother pathogens For instance preinfection with pathogenStaphylococcus aureus increases the vulnerability of the Celegans host by perverting its immune system which thenallows the opportunistic pathogen Proteus mirabilis to bepathogenic to this host [29] Also pore-forming toxins (PFTs)are important bacterial virulence factors and essential forthe pathogenesis of many Gram-positive and Gram-negativebacteria They act by poking holes in the plasma membraneof cells Besides horizontal gene transfer (HGT) betweenbacteria occurs in the intestinal tract of their animal hosts andfacilitates both virulence and antibiotic resistance [30] Last ithas been discovered that Orsay virus can infectC elegans andcause abnormal morphologies of C elegans intestinal cellsthemechanismunderneath this type of infection has not beenrevealed yet [7]

22 Tactics Employed by C elegans to Battle against PathogensA number of strategies are known to be used by C elegans tobattle against pathogens First C elegans owns mechanismsto avoid certain pathogens For example C elegans specif-ically avoids some strains of Serratia appertaining to theirproduction of the cyclic lipodepsipentapeptide serrawettinW2 This voidance behavior requires G protein signalingpathways and the sole C elegans Toll-like receptor TOL-1 [31] The hypothesis is further supported by the findingthat pathogen recognition through Toll-like receptors (TLRs)

ISRNMicrobiology 3









4 ISRNMicrobiology







ISRNMicrobiology 5


5 Outlook



References


















6 ISRNMicrobiology
































ISRNMicrobiology 7


























Volume 2014

Zoology






















Advances in

Virolog y



Volume 2014




Enzyme Research



Microbiology

ISRNMicrobiology 3









4 ISRNMicrobiology







ISRNMicrobiology 5


5 Outlook



References


















6 ISRNMicrobiology
































ISRNMicrobiology 7


























Volume 2014

Zoology






















Advances in

Virolog y



Volume 2014




Enzyme Research



Microbiology

4 ISRNMicrobiology







ISRNMicrobiology 5


5 Outlook



References


















6 ISRNMicrobiology
































ISRNMicrobiology 7


























Volume 2014

Zoology






















Advances in

Virolog y



Volume 2014




Enzyme Research



Microbiology

ISRNMicrobiology 5


5 Outlook



References


















6 ISRNMicrobiology
































ISRNMicrobiology 7


























Volume 2014

Zoology






















Advances in

Virolog y



Volume 2014




Enzyme Research



Microbiology

6 ISRNMicrobiology
































ISRNMicrobiology 7


























Volume 2014

Zoology






















Advances in

Virolog y



Volume 2014




Enzyme Research



Microbiology

ISRNMicrobiology 7


























Volume 2014

Zoology






















Advances in

Virolog y



Volume 2014




Enzyme Research



Microbiology








Volume 2014

Zoology






















Advances in

Virolog y



Volume 2014




Enzyme Research



Microbiology

review article host-microbe interactions in caenorhabditis ...pathogens both in the cell-autonomous...

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