PathogenicityPathogenicity

What makes some What makes some bacteria dangerous?bacteria dangerous?

Disease ProcessDisease Process

InfectionInfection

DiseaseDisease

Virulence factorsVirulence factors

No virulence factorsNo virulence factors

Silent infectionSilent infection

PathogenicityPathogenicity

SymptomsSymptomsEnvironmentEnvironment

Pathogenicity

Ability to cause disease - this is qualitative yes or no

Virulence - degree of pathogenicity

Requires that organism survive host

defenses cause damage Have virulence factors

Bacterial virulence factors for adherence, colonization, and invasiveness

VirulenceVirulence• varies with infectivity

and severity of damage Infectivity is often the

single most important feature; the microbe must be able to "stick" around• Attachment molecules

for bacteria are termed adhesins such as…..

Microbes often enter cells to establish as intracellular parasites

Some microbes move around the body from site of infection - invasiveness

Within cells that circulate Through cells- in and out Through junctions that

they weaken Cell entry of bacteria is

typically by phagocytosis• Professional

phagocytes• Non phagocytic cells

are induced to local phagocytosis (Type III secretion)

Salmonella entering gut cells

Spreading factors - enzymes to destroy intercellular cement

collagenase, hyaluronidase, fibrinolysin, lecithinase, streptokinase

Gangrene of the hand

Need to avoid host defenses to surviveNeed to avoid host defenses to survive Antiphagocytic factors

• Capsules, cell wall proteins• leukocidin• coagulase (walls off)• survival in WBC - intracellular parasites

(mycobacteria, Listeria) IgA protease - Neisseria Opportunistic pathogens need compromised host

N. meningitidis crosses blood-brain barrier

Need for iron to surviveNeed for iron to survive

How do bacteria damage the host?How do bacteria damage the host?

ENDOTOXIN vs ENDOTOXIN vs EXOTOXINEXOTOXIN

• Composition

LPS (lipidA) vs protein(immunogenic)

• Toxic response

fever and shock vs specific affect

• Typically produced bygram negatives vs gram positives and negatives

What is the mode of action of each of these exotoxins? diphtheria

tetanus botulism cholera pertussis Anthrax Samonella and E.coli

Botulism and tetanus are produced by Botulism and tetanus are produced by endospore-forming bacteriaendospore-forming bacteria

Cholera deaths are Cholera deaths are preventablepreventable

(iii) (iii) SalmonellaSalmonella

Salmonella typhimurium - rod prokaryote (dividing); note the flagella. Causes salmonellosis(food poisoning). (x 20,800) © Dr Dennis Kunkel, University of Hawaii. Used with permission

Based on genetic studies there is a single species ofSalmonella (Salmonella entericaSalmonella enterica).

Using appropriate antibodies more than 2000 antigenic "types" have been recognized.

Only a few types that are commonly associated with characteristic human diseases -

1. 1. S. enteritidisS. enteritidis

2. 2. S. cholerae-suisS. cholerae-suis

3. 3. S. typhiS. typhi

1.1. Salmonellosis Salmonellosis, the common salmonella infection,is caused by a variety of serotypes (most commonly S. enteritidisS. enteritidis) and is transmitted fromcontaminated food (such as poultry and eggs).

2. It does not have a human reservoir.

3. It usually presents as a gastroenteritis• nausea• vomiting• non-bloody stool

4. The disease is usually self-limiting (2 - 5 days).

Like Shigella, salmonellasalmonella invade the epithelium and do not produce systemic infection.

In uncomplicated cases of salmonellosis, which are the vast majority, antibiotic therapy is not useful.

S. cholerae-suis S. cholerae-suis (seen much less commonly)causes septicemiacauses septicemia after invasion.

In this case, antibiotic therapy is required.

The severest form of salmonella infectionsseverest form of salmonella infections is called"typhoid" or enteric fever.

Typhoid is caused by Salmonella typhiSalmonella typhi.

This disease is rarely seen in the Australia.

Typhoid is one of the historical causes of widespread epidemics and still causes epidemics inthe third world.

Salmonella typhiSalmonella typhi• The organism is transmitted from:

1. a human reservoir 1. a human reservoir

2. in the water supply (if sanitary conditions 2. in the water supply (if sanitary conditions are poor)are poor)

3. in contaminated food3. in contaminated food

• It initially invades the intestinal epithelium and during this acute phase, gastrointestinal symptoms are noted.

• The organisms penetrates (usually within the first week) and passes into the bloodstream where it is disseminated in macrophages.

• Typical features of a systemic bacterial infection are noted.

• The septicemia usually is temporary with the organism finally lodging in the gall bladder.

• Organisms are shed into the intestine for some weeks.

• At this time the gastroenteritis (including diarrhea) is noted again.

• A carrier state is common; thus one person e.g. a food handler can cause a lot of spread.

• Antibiotic therapy is essential.

• Vaccines are not widely effective and not generally used.

• The Vi (capsular) antigenVi (capsular) antigen plays a role in the pathogenesis of typhoid.

Pertussis toxin helps bacteria bind to Pertussis toxin helps bacteria bind to cilia and to kill cellscilia and to kill cells

Pentameric B subunit Pentameric B subunit delivers A subunit delivers A subunit

ADP-ribosylates ADP-ribosylates protein that is part of protein that is part of signal transduction signal transduction mechanism at cell mechanism at cell surfacesurface

Kills cells in Kills cells in respiratory tractrespiratory tract

Anthrax still poses a threatAnthrax still poses a threat

Three proteinsThree proteins• Lethal factor (LF)Lethal factor (LF)• Edema factor (EF)Edema factor (EF)• Protective antigen (PA)Protective antigen (PA)

PA binds forms a PA binds forms a heptamer to which EF heptamer to which EF and LF bindand LF bind

Endocytosis and pH Endocytosis and pH change cause fusion of PA change cause fusion of PA with vesicle and release of with vesicle and release of LF and EFLF and EF

Inhibit cell signalling and Inhibit cell signalling and cause cell deathcause cell death

Damage is often caused by the hostDamage is often caused by the host

Cytokine releaseCytokine release Antibody cross Antibody cross

reactionsreactions Immune complex Immune complex

depositiondeposition

What about viruses?What about viruses?

Adherence - access to cell with receptor Maintenance - ability to replicate Spread - no destruction in or out of cell Damage - lysis of cells, cytokine release,

cross reactions of immune response

Host DefensesHost Defenses

Innate Resistance - geneticInnate Resistance - genetic Nonspecific - Nonspecific - present at all times but varies

with portal of entry; directed against most bacteria

Specific immunity - Specific immunity - induced only after exposure; specific to the agent

Nonspecific defensesNonspecific defenses

Skin and mucous membrane surfaces • physical barriers

Characteristics of skin • dry and cool• low pH• chemicals - fatty acids,

lysozyme• competition from

normal flora• lymphoid cells beneath

surface - magainins

How does mucous membrane differ?How does mucous membrane differ?

Moist Warm Living Defended by

• Mucus

• Sloughing

• Chemicals

• Peristalsis/cilia

• Normal flora

• Immune cells/molecules - -magainins

Other chemical defensesOther chemical defenses

Complement

Phagocytes - neutrophil(PMN) monocyte Phagocytes - neutrophil(PMN) monocyte and macrophage (fixed or wandering)and macrophage (fixed or wandering)

Contain granules (lysosomes for digesting) • chemotaxis,• engulfment(phagos

ome);• fusion(phagolysoso

me);• Degranulation

Activation of Compliment by AntgensActivation of Compliment by Antgens“Classical pathway”“Classical pathway”

Inflammation Inflammation

Localizes infection and prevents spread. Localizes infection and prevents spread. Redness, swelling, pain and heat are due to vascular Redness, swelling, pain and heat are due to vascular

permeability which allows for phagocytic chemotaxis.permeability which allows for phagocytic chemotaxis.