Medical MicrobiologyMedical Microbiology

Chapter 19Chapter 19

Mechanisms of Bacterial Mechanisms of Bacterial PathogenesisPathogenesis

TermsTerms Pathology – study of diseasePathology – study of disease Etiology – cause of diseaseEtiology – cause of disease Pathogenesis – manner in which a Pathogenesis – manner in which a

disease developsdisease develops Infection – invasion or colonization of Infection – invasion or colonization of

the body by pathogenic the body by pathogenic microorganismsmicroorganisms

Disease – change from a state of Disease – change from a state of healthhealth

DiseasesDiseases How are diseases catagorized?How are diseases catagorized? Spread:Spread:

– CommunicableCommunicable– ContagiousContagious– NoncommunicableNoncommunicable

Categorization according to how often Categorization according to how often they occur in a given location:they occur in a given location:– endemic - constantly presentendemic - constantly present– epidemic - disease occurring in excess of epidemic - disease occurring in excess of

normal expectancynormal expectancy– Pandemic - worldwide epidemicPandemic - worldwide epidemic

DiseaseDisease

Severity or duration:Severity or duration:– AcuteAcute– ChronicChronic– LatentLatent

Extent of infection:Extent of infection:– Local infectionLocal infection– Systemic infectionSystemic infection– Bacteremia, septicemia, toxemia, Bacteremia, septicemia, toxemia,

viremiaviremia

DiseaseDisease

Primary infection vs. secondary Primary infection vs. secondary infectioninfection

Subclinical infectionSubclinical infection

Spread of DiseaseSpread of Disease

Etiology or etiological agent - cause of a Etiology or etiological agent - cause of a diseasedisease

Reservoir - continual source of pathogensReservoir - continual source of pathogens– human, animal, non-livinghuman, animal, non-living

Mechanisms of Transmission:Mechanisms of Transmission:– contact transmission - from one person to contact transmission - from one person to

another personanother person directdirect indirect (through a fomite)indirect (through a fomite) droplet (sneezing, coughing and talking)droplet (sneezing, coughing and talking)

Spread of Disease (cont.)Spread of Disease (cont.)

– Vehicle Transmission - transmission of Vehicle Transmission - transmission of disease by a mediumdisease by a medium

water, food, airwater, food, air

– Vector Transmission - transmission of Vector Transmission - transmission of disease by an insectdisease by an insect

Nosocomial infectionsNosocomial infections

EpidemiologyEpidemiology

Epidemiology is the study of the Epidemiology is the study of the frequency and distribution of frequency and distribution of diseasedisease– ExamplesExamples

The CDCThe CDC

The Centers for Disease Control and The Centers for Disease Control and Prevention (CDC) is the nation’s Prevention (CDC) is the nation’s center for epidemiology center for epidemiology – The CDC tracks some 50 infectious The CDC tracks some 50 infectious

diseases nationwidediseases nationwide– they help county and state agencies they help county and state agencies

during epidemicsduring epidemics– The CDC publishes a weekly newsletter The CDC publishes a weekly newsletter

called called Morbitity and Mortality WeeklyMorbitity and Mortality Weekly

Virulence FactorsVirulence Factors Successful pathogens have a variety of Successful pathogens have a variety of

factors that contribute to their ability to factors that contribute to their ability to cause diseasecause disease– these are called these are called virulence factorsvirulence factors

Mechanisms of Mechanisms of PathogenesisPathogenesis

Successful pathogens carry out a Successful pathogens carry out a sequence of events:sequence of events:– transmissiontransmission to a susceptible host to a susceptible host– gain gain accessaccess to the host to the host– adherenceadherence to the target tissue to the target tissue– colonizationcolonization and sometimes and sometimes invasioninvasion– damagedamage to the host to the host– exitexit from the hostfrom the host– transmissiontransmission to a new host to a new host

Mechanisms of Mechanisms of PathogenesisPathogenesis

TransmissionTransmission– Contact, vehicle, vector, etc.Contact, vehicle, vector, etc.

Access – Portals of EntryAccess – Portals of Entry– Mucous membranesMucous membranes– SkinSkin– Parenteral Route – through damage to Parenteral Route – through damage to

the skin or mucous membranesthe skin or mucous membranes– Table 19.1Table 19.1

Adherence and InvasionAdherence and Invasion Adherence:Adherence:

– AdhesinsAdhesins Many are found on fimbriaeMany are found on fimbriae Table 19-2Table 19-2

– CapsulesCapsules– BiofilmsBiofilms

Invasion – some pathogens can cross the Invasion – some pathogens can cross the mucous membranesmucous membranes

ColonizationColonization Colonization – bacteria can evade the immune Colonization – bacteria can evade the immune

system and replicate to cause disease.system and replicate to cause disease.– Antiphagocytic structuresAntiphagocytic structures::

Capsule – extremely important virulence factorCapsule – extremely important virulence factor– They are also poorly antigenic (polysaccharides)They are also poorly antigenic (polysaccharides)

Cell walls (mycobacteria)Cell walls (mycobacteria)

– Intracellular growthIntracellular growth– Antigenic variation – changing of antigensAntigenic variation – changing of antigens– Inactivation of antibodies or complementInactivation of antibodies or complement

DamageDamage Damage:Damage:

– EnzymesEnzymes– ToxinsToxins– Inappropriate Immune ResponsesInappropriate Immune Responses

Exaggerated inflammation (endotoxin)Exaggerated inflammation (endotoxin) Cross-reactive antibodies - strep throat Cross-reactive antibodies - strep throat

and rheumatic fever/glomerulonephritisand rheumatic fever/glomerulonephritis

EnzymesEnzymes Enzymes are released from cells and Enzymes are released from cells and

damage host tissuesdamage host tissues– Leukocidins - kill white blood cells Leukocidins - kill white blood cells – Hemolysins - cause the lysis of RBCsHemolysins - cause the lysis of RBCs

hemolysin - complete breakdown of RBCshemolysin - complete breakdown of RBCs hemolysin - incomplete breakdown of hemolysin - incomplete breakdown of

RBCsRBCs

– Streptokinase/Staphylokinase - breaks Streptokinase/Staphylokinase - breaks down blood clotsdown blood clots

How could this be related to virulence?How could this be related to virulence?

Enzymes (cont.)Enzymes (cont.)– Coagulase - causes the formation of Coagulase - causes the formation of

blood clotsblood clots almost all pathogenic strains of S. almost all pathogenic strains of S.

aureus produce this enzymeaureus produce this enzyme How does this contribute to virulence?How does this contribute to virulence?

– Collagenase - breaks down collagenCollagenase - breaks down collagen produced by the clostridia that cause produced by the clostridia that cause

gas gangrenegas gangrene– Proteases, hyaluronidase, Proteases, hyaluronidase,

phospholipase C, etc.phospholipase C, etc.

EndotoxinEndotoxin What is endotoxin? What is endotoxin?

– the lipid A portion of the lipid A portion of lipopolysaccharide (LPS) lipopolysaccharide (LPS)

Fever - elevated body temperatureFever - elevated body temperature Vasodilation (leading to shock) Vasodilation (leading to shock) InflammationInflammation can even result in deathcan even result in death

ExotoxinsExotoxins

These are substances released from These are substances released from bacteria that damage host tissues.bacteria that damage host tissues.

CytotoxinsCytotoxins - cause damage to cells - cause damage to cells– Erythrogenic toxins – (Erythrogenic toxins – (S. pyogenesS. pyogenes) )

damage cells lining capillaries and damage cells lining capillaries and cause blood to leak out under the cause blood to leak out under the skin (scarlet fever).skin (scarlet fever).

ExotoxinsExotoxins

EnterotoxinsEnterotoxins - cause damage to the - cause damage to the gastrointestinal tractgastrointestinal tract– diarrhea and vomitingdiarrhea and vomiting– Caused by electrolyte loss (resulting Caused by electrolyte loss (resulting

in water loss into the large intestine)in water loss into the large intestine) Cholera and some E. coli infections Cholera and some E. coli infections

(traveler’s diarrhea) – Figure 19-3 B(traveler’s diarrhea) – Figure 19-3 B staphylococcal food poisoningstaphylococcal food poisoning

Exotoxins (cont.)Exotoxins (cont.)

– Some enterotoxins also kill the cells Some enterotoxins also kill the cells lining the intestines causing lining the intestines causing dysentery dysentery (bloody diarrhea)(bloody diarrhea)

bacterial dysentery (bacterial dysentery (ShigellaShigella) and ) and E. coliE. coli O157:H7 infectionsO157:H7 infections

NeurotoxinsNeurotoxins - inhibit the normal - inhibit the normal functioning of the nervous systemfunctioning of the nervous system– Tetanus toxin (Tetanus toxin (Clostridium tetaniiClostridium tetanii) blocks ) blocks

inhibitory nerve impulses that allow inhibitory nerve impulses that allow muscles to relax muscles to relax

Lock JawLock Jaw

Exotoxins (cont.)Exotoxins (cont.)

– Botulinum toxin (Botulinum toxin (Clostridium botulinumClostridium botulinum) ) inhibits the functioning of motor neurons inhibits the functioning of motor neurons causing flaccid paralysis (muscles can’t causing flaccid paralysis (muscles can’t contract)contract)

– 1mg can kill 1,000,000 guinea pigs1mg can kill 1,000,000 guinea pigs– Figure 19-3 CFigure 19-3 C

Table 19-3Table 19-3

SuperantigensSuperantigens SuperantigensSuperantigens - toxins that stimulate - toxins that stimulate

non-specific activation of T-cellsnon-specific activation of T-cells– These then release large amount of These then release large amount of

cytokines leading to shockcytokines leading to shock

– toxic shock syndrome is caused by a toxic shock syndrome is caused by a superantigen produced by superantigen produced by Staphylococcus aureusStaphylococcus aureus

– can result in deathcan result in death– Figure 19-4Figure 19-4