BS1040 TOPIC 5: MICROBIAL PATHOGENESIS (LECTURE 1)

What is pathology?

The study of disease, involving the malfunction or disruption of a biological process or body part.

What is a pathogen?

A microorganism that can cause disease, typically including bacteria, viruses, fungi, and protozoa.

What defines a parasite?

An organism that lives on or in a host and is adapted to it, causing harm; usually larger multicellular organisms like protozoa, worms, fungi, insects, and plants.

What is pathogenesis?

the manner in which a disease develops

What is virulence?

ability to cause disease

What is virulence determinant?

A component that contributes to the virulence of an organism

Koch's four postulates

1. The microorganism must be present in all disease cases

2. The microorganism must be isolated from a diseased organism and grown in pure culture in vitro

3. The cultured microorganism is reproduced when its been inoculated into susceptible host

4. The microorganism is recovered from the experimentally-infected host and shown to be the same microorganism found in diseased host

molecular Koch's postulates

1. The phenotype under study should be associated with pathogenic strains of a species.

2. Specific inactivation of the suspected virulence gene(s) should lead to a measurable loss in virulence or pathogenicity. The gene(s) should be isolated by molecular methods.

3. Reversion or replacement of the mutated gene should restore pathogenicity.

issues and exceptions as shortcoming to Koch's postulates

1- asymptomatic carriers, sub-clinical infection so pathogen no associated with disease

2-some pathogens can't be cultured. theres no known media for some bacteria or appropriate host cell line for a virus

3-appropriate host model may not be available and use of primary host may not be ethical. so alternative hosts ma not reproduce disease accurately. host genotype or acquired immune its may reduce susceptibility

4-same issue of ability to culture

commensals

organisms that live together in close association and may or may not benefit each other

obligate/primary pathogens

Can cause disease regardless of individual's health

-overcome defenses to make host susceptible

Opportunistic pathogens

cause disease when the host's defenses are compromised or when they grow in part of the body that is not natural to them

zoonotic pathogens

have been transferred from other animals to humans but no apparent disease in humans

examples of obligate/primary pathogen

vibrio cholera and mycobacterium tuberculosis

Vibrio cholera

-causes high vol of watery diarrhoea

-cholera toxin is primary basis for diarrhoea

-death due to hypoyolemic shock

-untretaed <50% mortality

Mycobacterium tuberculosis

-causes tuberculosis

-tubercules in lungs lead to tissue necrosis and can spread to blood

-untreated with disease 50% mortality

HIV

-the virus that causes AIDS

-infects CD4+ lymphocytes

Treponema pallidum

causes syphilis, venereal disease and yaws

syphilis forms chancre's, spreads via lymphatics and blood

multistage disease lasting many years

Mycobacterium leprae

causes leprosy

target cell is Schwann cell- causes nerve damage

never grown in vitro. directly stained in samples

obligate intracellular pathogen

Uropathogenic E.coli

causes UTI

originates from gut microbiome

Pseudomonas aeruginosa

Common bacteria that can lead to a bacterial infection that appears as a green, yellow, or black discoloration on the nail bed.

infection of burns.

huge variety of different infections in many hosts

Staphylococcus aureus

gram positive cocci

complicated by AMR

problem in immunosuppressed and hospitalised

Clostridium difficile

only infects after dysbiosis due to AM use

can colonise neonates

Candida albicans

Fungi pathogen of gut flora

common infection of tongue piercing

Variety of severity and symptoms

-host specificity

-disease models in animals

-non-animal models

-variation in severity of clinical infection

-genotype of the host

-pre-existing immunity

-variation in pathogen virulence

what study used humans as models?

Tuskegee Syphilis study

Tuskegee Syphilis study

Research study conducted by a branch of the U.S. government

lasting for roughly 40 years (ending in the 1970s)

a sample of African American men diagnosed with syphilis were deliberately left untreated, without their knowledge, to learn about the lifetime course of the disease.

Mechanisms of pathogenesis

1.exotoxin production- external toxins that are relased from pathogens and damage cells

2.endotoxin- release of endotoxin from gram-negative bacterial LPS

3.cell invasion- cell death due to pathogen entering cell and replicating

4.immunopathological damage- immune response damaging host tissues- pathogens over trigger the immune responses

pathogenic processes

extracellular pathogens and intracellular pathogens

extracellular pathogens

Pathogens that exist outside host cells.

site of infection- epithelial surface, blood, lymph, interstitial spaces

examples- vibrio cholerae, neisseria, meningitidis

protective host responses- antibodies, antimicrobial peptides, complement, phagocytosis

Intracellular pathogens

pathogens that are able to grow and reproduce within eukaryotic host cells

site of infection- vesicular, cytoplasmic

examples- salmonella;a enteric, yersinia pestisis, listeria, viruses

protective host responses- cellular immunity (T cells and NK cells), activated macrophages

How is pathogenesis a multi layered process?

1. enter host

2. adhere

3. colonise

4. damage

5. avoid host defence mechanisms

6. transmit to other host

types of transmission

horizontal and vertical

horizontal transmission

disease is spread through a population from one infected individual to another (non-infected)

Examples:

- Aerosols

- Faecal-oral route

- Vector-borne

- Direct bodily contact

vertical transmission

parent to offspring

Examples:

- cross placenta

- birth canal

- germ line

Non specific host defences

- first line of defence

- ALWAYS there/done to prevent pathogens from entering

PHYSICAL BARRIERS

-skin

-epithilial layers

-mucus

-microbiome

-phagocytic cells

NON-PHYSICAL BARRIERS

-antimicrobial peptides

-acute phase proteins

-complement

-cytokines

colonisation requires overcoming host defence mechanisms to form a microcolony

-not targeted to a specific pathogen but is immediate

-innate immune system has pattern receptors- recognises things common to pathogens

-pathogens must avoid the innate immune response

Bacterial strategies to avoid non-specific HDM

1. tight junctions- avoid protease and motility

2. mucus- avoids chemotactic motility

3. microbiome- avoids anti-bacterial compounds

4. antimicrobial peptides- avoids capsule and LPS, biofilm formation

5. complement- avoids capsule and LPS, biofilm formation