Institute for Microbiology, Medical Faculty of Masaryk University Institute for Microbiology, Medical Faculty of Masaryk University and St. Anna Faculty Hospital in Brno and St. Anna Faculty Hospital in Brno

Miroslav VotavaMiroslav Votava

PATHOGENICITY AND PATHOGENICITY AND VIRULENCEVIRULENCE

Lecture for 2nd-year studentsLecture for 2nd-year studentsMarch 31March 31stst, 2008, 2008

Pathogenicity Pathogenicity = = AAbility of a microbe bility of a microbe to be to be harmfulharmful to to

health and to cause diseasehealth and to cause disease IInfectiousness nfectiousness = ability to cause infection= ability to cause infectionInfection Infection – broader term than disease– broader term than diseaseIn the disease In the disease symptoms of disease symptoms of disease are are

presentpresent (the infection is (the infection is manifest manifest one)one) But the infection may proceed without But the infection may proceed without

symptoms (symptoms (inapparent inapparent infection)infection)Apart from infections microbes can cause Apart from infections microbes can cause

foodfood poisoning poisoning,, as wellas well

Ecological remarkEcological remarkEcology Ecology = science on mutual relations among organisms = science on mutual relations among organisms

and relations between organisms and their environmentand relations between organisms and their environmentSymbiosis Symbiosis = close association of two di= close association of two differentfferent organisms organismsThree forms of symbiosis:Three forms of symbiosis: Mutualism Mutualism – both partners benefit from the association – both partners benefit from the association

and are unable to survive without itand are unable to survive without itCommensalism Commensalism – the association – the association is is beneficial for one beneficial for one

partner and indifferent to the other partner and indifferent to the other Parasitism Parasitism – the association benefits one partner and – the association benefits one partner and

harms the other (the host) harms the other (the host) → → consequence = consequence = pathogenicitypathogenicity

InfectionInfectionDefinition of infection is not an easy oneDefinition of infection is not an easy oneInfection Infection = situation when the = situation when the etiological etiological

agent agent of infection of infection invades invades an organism an organism and and multiplies multiplies in it; or it settles on bodily in it; or it settles on bodily surfaces and acts adversely theresurfaces and acts adversely there

Colonization Colonization = settlement of bodily = settlement of bodily surface by a surface by a nonpathogenicnonpathogenic microbe (or microbe (or by a pathogen that does not cause by a pathogen that does not cause pathological symptoms there)pathological symptoms there)

History of infectious diseasesHistory of infectious diseases – I – I Leviticus (3rd book of Moses) – ban of porkLeviticus (3rd book of Moses) – ban of porkQuarantine (40 days) – plague Quarantine (40 days) – plague Fracastoro (1485-1553): „De contagione“ Fracastoro (1485-1553): „De contagione“ 1676 Antony van Leeuwehoek – saw bacteria 1676 Antony van Leeuwehoek – saw bacteria 1838 Sch1838 Schönlein – mould in hair during favusönlein – mould in hair during favus1850 Davaine – bacteria in sheep with anthrax1850 Davaine – bacteria in sheep with anthrax1857 Pasteur – microbes → spoil wine and beer1857 Pasteur – microbes → spoil wine and beer1865 Villemin – micros1865 Villemin – microsccopically: bacteria in TBC opically: bacteria in TBC 1869 Pasteur – parasites in silkworm 1869 Pasteur – parasites in silkworm 1876 Lister – antisepsis 1876 Lister – antisepsis 1876 Robert Koch a1876 Robert Koch andnd Louis Pasteur – anthrax Louis Pasteur – anthrax

History of infectious diseasesHistory of infectious diseases – II – II

Physiological thesis of Hippocrates:Physiological thesis of Hippocrates:(Infectious) disease = consequence of certain (Infectious) disease = consequence of certain

inadequacy of organisminadequacy of organismMicrobial antithesis of Pasteur and Koch:Microbial antithesis of Pasteur and Koch:The cause of the infectious disease is a microbeThe cause of the infectious disease is a microbeEcological synthesis:Ecological synthesis:= synthesis of physiological thesis and microbial = synthesis of physiological thesis and microbial

antithesis – for the antithesis – for the occurenceoccurence of the of the infectious infectious diseasedisease the microbe, host and environment the microbe, host and environment are are responsibleresponsible

Koch´s postulatesKoch´s postulates

A particularA particular microbe is the etiological agent, if microbe is the etiological agent, if1.1. it is present in every case of the disease and its it is present in every case of the disease and its

localization in the body corresponds to localization in the body corresponds to the the damages observed;damages observed;

2.2. it is isolated from the host and kept in pure it is isolated from the host and kept in pure culture for several generations; culture for several generations;

3.3. by means of the microbe grown in this way it is by means of the microbe grown in this way it is possible to imitate the disease on another hostpossible to imitate the disease on another host;;

4.4. it is again isolated from the experimentally it is again isolated from the experimentally infected host.infected host.

Relationship between the Relationship between the microbe and the hostmicrobe and the host

Dynamic Dynamic and influenced by the and influenced by the environmentenvironment microbemicrobe host host

environmentenvironmentIllness is not a rule Illness is not a rule – – peaceful coexistence peaceful coexistence is is

usually better for the parasiteusually better for the parasiteIn spite of that the host tries In spite of that the host tries to get ridto get rid of the of the

parasiteparasite – to destroy, remove – to destroy, remove or at least or at least to localize itto localize it

PathogenicityPathogenicity

PathogenicityPathogenicity depends ondepends on bothboth microbial and microbial and host host speciesspecies

ParticularParticular microbial species is microbial species is pathogenicpathogenic for for a specific host species only, for another a specific host species only, for another species it may be species it may be non-pathogenicnon-pathogenic

This host species is This host species is susceptible susceptible to the to the relevant microbial species, to relevant microbial species, to aa different different microbial species it can be microbial species it can be resistantresistant

Primary and opportune pathogensPrimary and opportune pathogens Primary (obligate) pathogens →Primary (obligate) pathogens → disease also disease also

in otherwise healthy individuals: chiefly in otherwise healthy individuals: chiefly agents of agents of classical infectionsclassical infections (diphtheria, (diphtheria, typhoid fever, plague, gonorrhea, tetanus, typhoid fever, plague, gonorrhea, tetanus, influenza, morbilli etc.)influenza, morbilli etc.)

Opportunistic (facultative) pathogens →Opportunistic (facultative) pathogens → disease under certain conditions or at a disease under certain conditions or at a certain disposition only: usually members certain disposition only: usually members of of normal floranormal flora

• when they reach another site in the body when they reach another site in the body • or when the immunity of the individual is or when the immunity of the individual is

loweredlowered

Natural and experimental Natural and experimental pathogenicitypathogenicity

Microbes naturally pathogenic Microbes naturally pathogenic forfor man man && animals:animals:Staph. aureus, Francisella tularensis, Clostridium Staph. aureus, Francisella tularensis, Clostridium

botulinum, botulinum, rabies v., tick-borne encephalitis v.rabies v., tick-borne encephalitis v.Microbes pathogenic for animals experimentally:Microbes pathogenic for animals experimentally:Bacillus anthracis, Streptococcus pneumoniae, Bacillus anthracis, Streptococcus pneumoniae,

Clostridium tetani –Clostridium tetani – mouse mouse Mycobact. tuberculosis, Mycobact. tuberculosis, rickettsiaerickettsiae – – guinea pigguinea pig Treponema pallidum, Treponema pallidum, herpes simplex v. – rabbit herpes simplex v. – rabbit MiMiccrobes pathogenic for man only: robes pathogenic for man only: Neisseria gonorrhoeae, Haemophilus ducreyiNeisseria gonorrhoeae, Haemophilus ducreyiMiMiccrobes non-pathogenic for man:robes non-pathogenic for man:Majority of soil and water microorganismsMajority of soil and water microorganisms

Opportunistic pathogens – IOpportunistic pathogens – I

TypicalTypical opportunistic pathogen: opportunistic pathogen:Escherichia coliEscherichia coli

A part of normal colonic flora (but 1 % only)A part of normal colonic flora (but 1 % only)Outside the large intestine = pathogenOutside the large intestine = pathogen• cystitis, pyelonephritis, urosepsiscystitis, pyelonephritis, urosepsis• cholecystitis, peritonitischolecystitis, peritonitis• wound infectionswound infectionsAt lowered immunity (newborns): At lowered immunity (newborns): • meningitismeningitis • diarrhea (EPEC – serotypes O55, O111)diarrhea (EPEC – serotypes O55, O111)

Opportunistic pathogens – IIOpportunistic pathogens – IIAnotherAnother opportunistic pathogen: opportunistic pathogen:

Staphylococcus epidermidisStaphylococcus epidermidisPart of normal skin and mucosal floraPart of normal skin and mucosal floraOutside the skin and mucosae = pathogenOutside the skin and mucosae = pathogen• wound infections (also surgical: sternum, eye)wound infections (also surgical: sternum, eye)• cystitiscystitisAt lowered immunity:At lowered immunity:• above all blood stream infections in individuals above all blood stream infections in individuals

with i.v. catheters, infections of implants and with i.v. catheters, infections of implants and other devicesother devices

• sepsis in newborns and neutropenic individuals sepsis in newborns and neutropenic individuals

Virulence Virulence

VirulenceVirulence = = degreedegree (measure) (measure) of pathogenicityof pathogenicityVirulenceVirulence = property of certain = property of certain strainstrain – a pathogenic – a pathogenic

species can incorporate species can incorporate highly virulent strains highly virulent strains as well as almost as well as almost avirulent avirulent onesones

Indicator of strain virulence:Indicator of strain virulence: ability to kill ability to killLDLD5050 = 50% lethal dose (the amount of microbe that = 50% lethal dose (the amount of microbe that

is able to kill exactly ½ of experimental animals)is able to kill exactly ½ of experimental animals)Increasing virulence: Increasing virulence: repeated passages of the repeated passages of the

strain (be cautious with the strains from strain (be cautious with the strains from dissection material)dissection material)

Attenuation Attenuation = artificial = artificial weakening of virulenceweakening of virulence

AttenuationAttenuation

BCG-vaccine BCG-vaccine (bacille Calmette-Guérin) (bacille Calmette-Guérin) against TBCagainst TBCOriginal strain: Original strain: Mycobacterium bovisMycobacterium bovis – – is less is less

pathogenic for man than pathogenic for man than Mycob. tuberculosisMycob. tuberculosisThe selected The selected strain was tormented 12 years on strain was tormented 12 years on

potato with bilepotato with bile until it lost most of its virulence until it lost most of its virulence (it is almost avirulent)(it is almost avirulent)

InIn a normal newborn a normal newborn BCGBCG causes causes only a local only a local processprocess in the site of injection or in a regional in the site of injection or in a regional lymph nodelymph node

Very rarely in an Very rarely in an immunodeficient newbornimmunodeficient newborn it can it can cause the cause the generalized infectiongeneralized infection

MICROBEMICROBE obligatelyobligately opportunistically opportunisticallySpecies:Species: pathogenic pathogenic non-pathogenicpathogenic pathogenic non-pathogenic

Strain:Strain: virulent avirulentvirulent avirulent

Individual:Individual: sensitive nonspecifically unresponsive sensitive nonspecifically unresponsive or specifically immuneor specifically immune

Species:Species: susceptible susceptible resistantresistant

HOSTHOST

Recommended reading materialRecommended reading material

Paul de Kruif: Microbe HuntersPaul de Kruif: Microbe HuntersPaul de Kruif: Men against DeathPaul de Kruif: Men against DeathAxel Munthe: The Story of San MicheleAxel Munthe: The Story of San MicheleSinclair Lewis: ArrowsmithSinclair Lewis: ArrowsmithAndré Maurois: La vie de Sir Alexander André Maurois: La vie de Sir Alexander

FlemingFlemingHans Zinsser: Rats, Lice, and HistoryHans Zinsser: Rats, Lice, and History

Thank you for your attentionThank you for your attention