Bacterial pathogenesis

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Bacteria and disease Terminology

Pathogen- a microbe that harms the host/causes diseases

Commensal- a microbe that dent cause harm and is typically considered part of the normal flora

Saprophyte- feeds and decomposes dead organic material

Infection -

Infectious Disease -

Pathogenesis of a disease- is the biological mechanism that leads to the diseased state

Virulence- the relative ability of a pathogen to cause disease in the host

Opportunistic pathogen- can be part of the normal flora but may be harmful if they move from one part of the body to another

Strict pathogen -

Colonisation-

Slides 3 an 4

How bacteria cause disease

Billions of microbes in / on body

Most beneficial even essential roles for health

Other microbes may bring about damage to host

Host- pathogen relationships are dynamic as each can modify functions and activities of the other

Pathogens have a range of virulence that allows them to bring about disease

Most bacteria never pathogenic

Some potentially pathogenic

Few always pathogenic

Pathogenesis

2 major components

Virulence factors that damage or alter host cells and tissues

Host repose (immune and inflammatory response ) that may lead to disease

Pathogen host interaction

Steps

Exposure

Adherence

Invasion

Colonisation

Invasiveness and Additional virulence factor interaction with host molecules

Tissue damage - disease

Host determinants

Species

Breed

Age

Sex

Genetic factors

Physiological factors

Nutrition

Malnourished? etc

Immune competence

Pathogen determinanats

Virulence

Environmental stability

Route of entry

Infective dose

Tissue tropism

Some bacteria prefer certain tissues

Susceptibility to host defence

Virulence factors

Mechanisms / products of pathogens that promote their ability to cause infection and disease

Include outer membrane proteins, endotoxins etc

Could be types

Factors promoting colonisation / invasion of host

Factors causing damage of host

Identification of pathogen virulence include including virulence factor gene knock outs in bacteria then subjecting an animal disease model

Examples

Plasmid - not always

Bacteriophages

Flagellum

Exotoxins

Endotoxins - released on death of cell

Proteases

Siderophores - harvest iron from other sources

Capsule

Pili

Adhesions

Lipoysaccharide

Koch's Postulates

Developed tests to assess germ theory

This was enabled by culture methods for microorganism growth that Pasteur developed

Bacillus anthraces was first bacteriaum proven to be the causative agent for a disease, anthrax

Also discovered agents of cholera and tuberculosis

Steps

Microbe should be found in all cases and at all sites of disease

Microbe isolated from infected persons and maintained in pure culture

Pure cultured microbes should cause symptoms of disease on inoculation into a susceptible individual

Microbe should be preisolated from intentionally infected host

Provided solid conceptual basis for understanding ID

Limitations

Viruses/some bacteria/parasites can't grow independent of host

Asymptomatic carriers

Opportunistic pathogens

Polymicrobial diseases

Identifying virulence factors - molecular level (Falkow)

Phenotype under investigation should be associated with pathogenic members of a genus or pathogenic strains of species

Specific inactivation of genes associated wth a suspected virulence trait should lead to measurable loss in virulence

Reactivation of mutated gene should lead to restoration of pathogenicity

Implementation

Either use original host or make murine model of disease

Isolate bacteria , make mutant bacteria . then reintroduce mutant and will type ???

Slide 16

Adherence

To skin or mm

Specific to epithelial cells

???slide 17

Invasion

Slide 18

Intracellular

Invade and survive within immune system associated phagocytic cells

Trojan horse tactic enabling transport to other tissues

Colonisation and growth

Pathogen must fine relevant environment for growth

Some remain localised producing small focus of infection

Generalised. infections occur due to bacteraemia - pat

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Secreted virulence factors

Secreted extracellular proteins can aid establishments and maintenance of pathogens

Often break down host tissue

Coagulase

Proteases

Nucleases

Leukocidins

Haemolysins

Coagulase test

Causes blood clotting

Mix dense liquid suspension of bacteria wit plasma , incubate and look for clot

Endotoxins

Endotoxin -

Can spread from site of infect??

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Bacterial toxins

Can be important for survival in host

Proteins responsible for many symptoms caused by pathogens during infection

Slide 24?

How bacteria become pathogenic

Transformation - uptake of naked DNA from environment

Conjugation - direct transfer of plasmid DNA

Transduction- DNA transfer mediated by bacteriophages

Plasmids and conjugation

Slide 26

Transmission of DNA between bacteria

DNA transferred as plasmids

Undirectional

Plasmids can carry virulence genes

Also responsible for transfer of AMR

Bacteriophages

Help to transfer virulence factors

Can cause bacteria to become pathogenic

Mobile genetic elements

Transposable genetic elements

Pathogenicity islands

Uropathogenic

Commensal -- pathogen

Pathogenicity islands added to commensal bacteria

Then able to cause infections