07 pathogenicity and_virulence

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 Votava, Vladana WoznicováMiroslav Votava, Vladana Woznicová

PATHOGENICITY AND PATHOGENICITY AND VIRULENCEVIRULENCE

Lecture for 2nd-year studentsLecture for 2nd-year studentsMarch 3March 300, 200, 20099

Pathogenicity Pathogenicity

= = AAbility of a microbe bility of a microbe to be to be harmfulharmful to health and to health and to cause diseaseto cause disease

IInfectiousness nfectiousness = ability to cause infection= ability to cause infection

Infection Infection – broader term than disease– broader term than disease

In the diseaseIn the disease,, symptoms of disease symptoms of disease are presentare present (the infection is (the infection is manifest manifest one)one)

But the infection may proceed without symptoms But the infection may proceed without symptoms ((inapparent inapparent infection)infection)

Apart from infectionsApart from infections,, microbes can cause food microbes can cause food poisoningpoisoning,, 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 organisms

Three forms of symbiosisThree forms of symbiosis::

Mutualism Mutualism – – bothboth partners partners benefitbenefit from the association from the association and are unable to survive without itand are unable to survive without it

Commensalism Commensalism – the association – the association is is beneficial for one beneficial for one partner and indifferent to the otherpartner and indifferent to the other

Parasitism Parasitism – the association – the association benefits one partner and benefits one partner and harms the otherharms the other (the host) (the host) → → consequence = consequence = pathogenicitypathogenicity

InfectionInfection

Definition of infection is not an easy oneDefinition of infection is not an easy one

Infection Infection = situation when the = situation when the etiological agent etiological agent of infection of infection invades invades an organism and an organism and multiplies multiplies in it; or it settles on bodily surfaces in it; or it settles on bodily surfaces and acts adversely thereand acts adversely there

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

History of infectious diseasesHistory of infectious diseases

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

inadequacy of organisminadequacy of organism

Microbial 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 microbe

Ecological 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, if

1.1. it is present it is present in every casein every case of the disease and its 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 it is isolated from the hostisolated from the host and kept in pure 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 possible to imitate the disease on another hostdisease on another host;;

4.4. it is it is again isolatedagain isolated from the experimentally 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 – peaceful coexistence is Illness is not a rule – peaceful coexistence 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 in disease also in otherwise healthy individuals: chiefly agents of otherwise healthy individuals: chiefly agents of classical infectionsclassical infections (diphtheria, typhoid fever, (diphtheria, typhoid fever, plague, gonorrhea, tetanus, influenza, morbilli plague, gonorrhea, tetanus, influenza, morbilli etc.)etc.)

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

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

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, Clostridium Bacillus anthracis, Streptococcus pneumoniae, Clostridium

tetani –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 ducreyi

MiMiccrobes 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 infections

At lowered immunity (newborns): At lowered immunity (newborns): • meningitismeningitis • diarrhea (EPEC – serotypes O55, O111)diarrhea (EPEC – serotypes O55, O111)

S. aureus bacteria escaping destruction by human white blood cells

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Opportunistic pathogens – IIOpportunistic pathogens – II

AnotherAnother opportunistic pathogen: opportunistic pathogen:Staphylococcus epidermidisStaphylococcus epidermidis

Part 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)• CystitisCystitis

At 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 pathogenicity

VirulenceVirulence = 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 kill

LDLD5050 = 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 TBC

Original strain: Original strain: Mycobacterium bovisMycobacterium bovis – – is less is less pathogenic for man than pathogenic for man than Mycob. tuberculosisMycob. tuberculosis

The 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 Hunters

Paul de Kruif: Men against DeathPaul de Kruif: Men against Death

Axel Munthe: The Story of San MicheleAxel Munthe: The Story of San Michele

Sinclair Lewis: ArrowsmithSinclair Lewis: Arrowsmith

André Maurois: La vie de Sir Alexander André Maurois: La vie de Sir Alexander FlemingFleming

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

Thank you for your attentionThank you for your attention