(2.2) Pathogenesis of Bacterial Infection and Normal Human Microbiota

pathogenesis of bacterial infection

Initiation of the infectious process and the mechanisms that lead to the development of signs and symptoms of disease

The organism must ALWAYS be found in humans with the infectious disease but not found in healthy ones.

What is the 1st criterion of Koch’s postulates?

The organism must be ISOLATED from humans with the infectious disease and grown in pure culture.

What is the 2nd criterion of Koch’s postulates?

The organism isolated in pure culture must INITIATE DISEASE when re-inoculated into susceptible animals.

What is the 3rd criterion of Koch’s postulates?

The organism should be RE-ISOLATED from the experimentally infected animals.

What is the 4th criterion of Koch’s postulates?

Invasion, transmissibility, adherence, persistence, immune evasion, and toxigenicity

What are the major characteristics of pathogenic bacteria?

Pathogenicity

The ability of an infectious agent to cause disease.

virulence

The quantitative ability of an agent to cause disease

Virulent agents

_________________cause disease when introduced into the host in small numbers.

Adherence + persistence + invasion + toxigenicity

What characteristics contribute to bacterial virulence?

Microbiota

Microbial flora harbored by normal, healthy individuals.

Pathogen

A microorganism capable of causing disease.

Pathogen

A microorganism that does not cause disease; may be part of the normal microbiota.

Opportunistic pathogen

An agent capable of causing disease only when the host’s resistance is impaired (immunocompromised)

Normal skin and mucous membranes

What provides the primary defense against infection?

Sites where mucous membranes meet the skin

What are the most frequent portals of entry for pathogenic bacteria?

Upper and lower airways

What are the main respiratory portals of entry?

Mouth

What is the primary gastrointestinal portal of entry?

Genital and urinary tracts

Which reproductive and excretory tracts can serve as portals of entry?

Cuts, burns, and other skin or mucous membrane injuries

What abnormal areas can serve as portals of entry for pathogenic bacteria?

Animal pathogens can be transmitted to humans through animals or animal products

How can animals serve as a source of human infection?

Salmonella + Campylobacter

Which bacteria can be transmitted to humans through contaminated animal food products?

Bloody diarrhea

What gastrointestinal disease is commonly associated with Campylobacter infection?

Rodents + rodent fleas → flea transmission to humans

What is the natural reservoir and mode of transmission of Yersinia pestis?

Animal products such as raw hair from infected animals

How is Bacillus anthracis transmitted from animals to humans?

C. perfringens → gastroenteritis; C. botulinum → botulism

How can Clostridium species be transmitted through ingestion?

C. perfringens → gas gangrene; C. tetani → tetanus

How can Clostridium species cause infection through contaminated wounds?

Improper preparation, sanitation, or cooking of animals and animal products

What increases the risk of animal-derived infections in humans?

diarrhea, cough, and genital discharge help spread microorganisms

How do clinical manifestations of infectious diseases promote transmission?

Contaminated water or seafood

How is Vibrio cholerae transmitted?

Profuse “rice-water” diarrhea → contaminates water sources

How does Vibrio cholerae promote its own transmission?

Food contaminated with sewage containing E. coli → diarrhea → bacterial transmission

How is Escherichia coli transmitted through food?

Respiratory aerosols produced by coughing

How is Mycobacterium tuberculosis transmitted?

Humans

What is the natural host of Mycobacterium tuberculosis?

Hands

How are many bacteria commonly transmitted from one person to another?

Nose → hands → other body sites or another person

How can Staphylococcus aureus be spread from a person with nasal carriage?

Anterior nares

Where is Staphylococcus aureus commonly carried?

colonization

Establishment of a stable bacterial population on the skin or mucous membranes

Mucosal surface

Where does the initial interaction between bacteria and host tissue usually occur?

Adhesion to the mucosal cell surface

What is normally required for bacterial colonization?

bacterial colonization

____________ allows for the establishment of a focus of infection that may remain localized or spread to other tissues

Adherence factors, toxins, enzymes, antiphagocytic factors, intracellular pathogenicity, iron requirement, antigenic heterogeneity (ATE AIRA)

What are the major virulence factors of bacteria?

Essential for colonization and penetration through tissues

What is the role of adherence factors in bacterial virulence?

adherence factors

____________Prevent removal by innate defenses such as gut peristalsis and flushing by mucus, saliva, and urine

Surface hydrophobicity + net surface charge

What nonspecific bacterial surface properties contribute to the initial stages of adhesion?

↑ Hydrophobicity → ↑ adherence

How does increased bacterial surface hydrophobicity affect adherence?

Both have a net negative surface charge

Why do bacteria and host cells have repulsive electrostatic forces?

Bacterial ligands + host cell receptors

What are the two major components involved in specific bacterial adherence?

pili

Long, thick, rod-like appendages used for bacterial attachment; mainly found in Gram-negative bacteria

Type 1 pili

What type of pili does E. coli use for adherence to epithelial cell receptors?

D-mannose

What can block Type 1 pili-mediated adherence of E. coli in vitro?

P-pili

What type of pili is commonly associated with E. coli causing UTIs?

fimbriae

Short, thin, hair-like structures that mediate bacterial adherence to host cells

Gram-positive and Gram-negative bacteria

Where can fimbriae be found?

Fimbriae-mediated adherence

How do diarrheagenic E. coli adhere to intestinal epithelial cells?

Fimbriae

What structures help Group A Streptococcus adhere to buccal epithelial cells?

Lipoteichoic acid + Protein F + M protein

What components are found in Group A Streptococcus fimbriae?

Fibronectin

What mediates the adherence of lipoteichoic acid and Protein F of Group A Streptococcus to buccal epithelial cells?

M protein

What bacterial protein is important for Group A Streptococcus adherence to buccal epithelial cells?

Host cell receptor interactions

What determines the outcome after bacterial ligands bind to host cell receptors?

invasion in bacterial infection

Penetration of bacteria into host cells and tissues

Invasion of the host epithelium

What is central to the infectious process and allows bacteria to enter host tissues?

Invasins

What bacterial factors mediate invasion?

invasins

Bacterial surface or secreted proteins that target host cell receptors

exotoxins

Protein toxins usually secreted by bacteria that modify or destroy cellular structures

Acute onset due to their high potency

When are the effects of exotoxins usually seen?

Inhibits acetylcholine release → flaccid paralysis

What is the mechanism of botulinum toxin?

Botulism, anthrax, cholera, diphtheria

What are examples of diseases caused by exotoxins?

endotoxins

Lipid components of the bacterial cell membrane, particularly LPS

Gram-negative bacteria

Which type of bacteria contains lipopolysaccharide (LPS) endotoxin?

Excreted by living bacterial cells

Where are exotoxins found?

Gram-positive and Gram-negative bacteria

Which bacteria produce exotoxins?

Polypeptides

What is the chemical composition of exotoxins?

Relatively unstable; toxicity is often destroyed above 60°C

How stable are exotoxins to heat?

Highly immunogenic → stimulate high-titer antitoxin

How immunogenic are exotoxins?

Toxoids

What can exotoxins be converted into for immunization?

Tetanus toxoid

What is an example of an exotoxin converted into a toxoid?

Highly toxic; can be fatal in microgram quantities or less

How toxic are exotoxins?

Bind to specific cellular receptors

How do exotoxins usually act on host cells?

Naur

Do exotoxins usually cause fever?

Extrachromosomal genes, such as plasmids

Where are the genes encoding exotoxins commonly located?

Integral part of the cell wall of Gram-negative bacteria

Where are endotoxins found?

during bacterial death and partly during bacterial growth

When are endotoxins released?

Lipopolysaccharide (LPS); lipid A causes toxicity

What is the chemical composition of endotoxins?

Relatively stable; can withstand >60°C for hours

How stable are endotoxins to heat?

Weakly immunogenic

How immunogenic are endotoxins?

Nour

Can endotoxins be converted into toxoids?

Moderately toxic; fatal in tens to hundreds of micrograms

How toxic are endotoxins compared with exotoxins?

No specific receptors

Do endotoxins bind to specific cellular receptors?

Release of IL-1 and other inflammatory mediators

How do endotoxins cause fever?

Chromosomal genes

Where are the genes responsible for endotoxin synthesis located?

Contamination with soil or feces

How are Clostridium perfringens spores introduced into wounds?

Necrotic tissue → anaerobic environment

What condition allows C. perfringens spores to germinate and produce toxins?

Necrotizing + hemolytic toxins

What toxins contribute to the development of gas gangrene?

Gas formation + impaired blood supply + tissue distention

What factors, together with toxins, contribute to gas gangrene?

Lecithinase

What is the alpha toxin of C. perfringens?

Splits lecithin → phosphorylcholine + diglyceride

How does the alpha toxin damage cell membranes?

Necrotizing effect

What is the effect of the theta toxin?

Damage connective tissue matrix → loosen tissue fibers → facilitate bacterial spread

How do collagenases and DNases contribute to C. perfringens infection?

Binds to host cells and mediates toxin adherence

What does the B subunit of an A-B type toxin do?