Bacterial Pathogenesis

Question 1

PRIMARY PATHOGENS

Answer 1

Will almost always cause disease if delivered to an appropriate host (eg. non-vaccinated) by an appropriate route, in SUFFICIENT QUANTITIES.

Question 2

SECONDARY PATHOGENS

Answer 2

Are more likely to cause disease if the host has been ‘prepared’ for them eg. Secondary bacterial infection is seen after a cold, when the host is still immunocompromised.

Question 3

OPPORTUNISTIC PATHOGENS

Answer 3

These rarely cause disease in the healthy animal, but can cause disease in hosts who’s defenses are compromised. eg. HIV positive.

Question 4

PATHOGENESIS

Answer 4

All the processes and mechanisms by which disease develops from a pathogenic organism infecting a host.

Question 5

INFECTIVITY

Answer 5

Reflects the ability of an organism to enter, colonise and survive within a host. How easily an organism causes infection. An organism can have low virulence but high infectivity eg. Bordatella bronchiseptica (and vice versa- Tetanus in horse)

Question 6

VIRULENCE

Answer 6

A measure of the capacity to damage/kill the host. Very virulent organisms will kill a high proportion of infected animals. eg. Tetanus in horses has low infectivity, but high virulence.

Question 7

VIRULENCE FACTOR

Answer 7

Any component of the bacteria which is involved in pathogenesis, virulence, or infectivity.

Question 8

REPRODUCTION

Answer 8

Occurs after the bacteria has encountered, entered and colonised the host.

It must join with the host tissues before colonisation or will be eliminated by host defense mechanisms (eg. mucous flow along alimentary tract- mechanical)

Reproduction requires NUTRIENTS and RESISTANCE TO HOST ATTEMPTS AT ELIMINATION.

Question 9

TRANSMISSION TO A NEW HOST

Answer 9

Can be DIRECT- animal->animal

or INDIRECT- via the environment.

Some bacteria cannot survive in the environment, so MUST undergo direct transmission.

Others can survive for long periods of time in the environment eg. Food poisoning bacteria.

Question 10

KOCH’S POSTULATES

Answer 10

Allows us to determine whether a microorganism is the actual source of disease.

1. THE ORGANISM OR IT’S PRODUCTS SHOULD BE FOUND IN ALL INDIVIDUALS WITH THE DISEASE.
2. THE ORGANISM SHOULD BE ISOLATED AND BE ABLE TO BE MAINTAINED IN PURE CULTURE.
3. THE PURE CULTURE INOCULATED IN TO AN INDIVIDUAL SHOULD CAUSE DISEASE.
4. ORGANISM SHOULD BE REISOLATED IN PURE CULTURE.

Disease->Isolation->Reinfection->Reisolation.

These steps do not apply to all microorganisms but were invaluable in identifying many of the classic diseases.

Question 11

VIRULENCE FACTOR IDENTIFICATION

Answer 11

Molecular ID is most common. Potential virulence genes are inactivated and their effects studied.

OR virulence genes are isolated and inserted in to avirulent strains, with the effects studied.

Epidemiological ID- Does the presence of a virulence factor correlate with disease?

Biochemical- A putative virulence factor is isolated and studied in vitro and in vivo (PURIFIED v. factors are injected for live studies)

Question 12

FACTORS INFLUENCING THE OUTCOME OF CONTACT BETWEEN PATHOGEN AND ANIMALS

Answer 12

The balance between host and pathogen will determine the outcome of an interaction between the two (disease/no disease).

Host defences- See previous lecture.

Others: COMMENSAL FLORA- affects host.

Established shortly after birth, seen throughout the body and persists throughout life (with fluctuations).

Normal flora in the gut is important in resistance to pathogenic infection.

Particular populations of commensal flora are associated with particular diseases.

Composition of flora is different in disease and health.

Question 13

STRATEGIES OF PATHOGENIC BACTERIA

Answer 13

Of course bacteria must first contact, enter and colonise the host. These do not causes disease.

ADHERENCE- Avid adherence is required for most pathogens to be successful. Particularly important for pathogens at mucosal surfaces.

Several different strategies are available, most bacteria use more than one:

1. Commensal bacteria in respiratory areas adhere to mucous, and replicate faster than they are removed by mucous flow.
2. Carbohydrate binding domains on the end of pili/fimbriae bind to carbohydrate molecules in the surface of epithelial cells. eg. E. coli F4/K88 fimbriae.
3. Bacteria bind to the polypeptide part of surface glycoproteins. eg. Invasin protein of Y. enterocolitica binds to B integrins.
4. Bacteria bind to extracellular matrix proteins, which then bind to a surface receptor on the epithelial cell. eg. GRAM POSITIVES.

Some bacteria exhibit tropism for colonising and adhering to particular tissues.

Question 14

EXTRACELLULAR LIFECYCLE

Answer 14

Contact

Entry

Colonisation

Attachment

Resists phagocytosis

**Acquires nutrients. **

eg. E. coli, A. pleuropneumoniae, B. anthracis, Clositridia, S. aureus, Streptococci, Mycoplasma.

Question 15

INTRACELLULAR LIFECYCLE

Answer 15

Contact

Entry

Colonisation

Attachment

Invasion

Resists intracellular destruction

Acquires nutrients

eg. Mycobacteria, L. monocytogenes, Salmonella, Brucella, Chlamydia, Rickettsia.

Intra and extracellular pathogens will have different nutrients available to them.

Question 16

EXOTOXINS

Answer 16

These are particularly seen in extracellular pathogens.

Highly toxic proteins that affect phagocytes.

May lyse red blood cells in vitro (plates)- Haemolysis.

This may not occur in vivo with natural infection; at these concentrations, phagocytes are being acted on by haemolysins, not RBCs.

Haemolysin action on phagocytes causes:

• Phagocyte lysis
• Inhibition of phagocytosis, chemotaxis and/or degranulation.

Question 17

IRON

Answer 17

Iron is essential for infection by most bacteria and fungi.

Mammalian extracellular fluid contains iron, but it is complexed to binding proteins so levels are far too low.

Transferrin and Lactoferrin.

Question 18

TRANSFERRIN

Answer 18

Serum protein that binds iron in the host animal

Question 19

LACTOFERRIN

Answer 19

Mucosal surface and neutrophil protein that binds iron in the host animal.

Question 20

HYPOFERRAEMIA OF INFECTION

Answer 20

During infection, plasma iron levels are lowered even further, BY THE HOST.

This aims to starve pathogens of iron.

It is a form of nutritional immunity.

Question 21

SIDEROPHORES

Answer 21

These are low molecular weight iron chelators.

High affinity for iron- Can strip it from host Tf and Lf.

An iron loaded siderophore is recognised by a cognate ferric siderophore receptor on the bacteria surface.

Iron is then transported in to the cell.

Siderophore action is not host specific- Siderophores can scavenge iron from most mammalian species.

Question 22

DIRECT Tf/Lf BINDING

Answer 22

This uses transferrin or lactoferrin binding proteins.

These bind to bacterial surfaces.

Tf/Lf then bind to these receptors and are stripped of iron, which is transferred to the cell.

Direct Tf/Lf binding is very host specific. It will work with iron binding proteins from ONE species or from VERY CLOSELY RELATED species.

Question 23

DOES IRON SCAVENGING MECHANISM MATTER?

Answer 23

MAYBE- Due to host specificity (low in siderophores, high in direct Tf/Lf binding)

The method of iron binding used may influence host specificity and host range size of a pathogen.

Question 24

STRATEGIES USED BY INTRACELLULAR PATHOGENS

Answer 24

Intracellular pathogens must adhere, invade, reproduce, obtain nutrients.

Many intracellular pathogens can survive inside macrophages.

This has advantages:

LONG LIVED

SAFE FROM EXTRACELLULAR MACROPHAGES

RICH NUTRIENT SUPPLY

MOBILE- Aids in dissemination

Bacteria enter the cell in phagosomes, then must use various strategies to ensure survival.

Question 25

STRATEGIES USED BY INTRACELLULAR PATHOGENS

Answer 25

Bacteria enter the cell in phagosomes, then must use various methods to ensure survival:

ESCAPE FROM PHAGOSOME- toxins on the surface iff the bacteria allow lysis of the phagosome membrane, allowing the bacteria to escape in to the cytoplasm of the host cell. *L. monocytogenes, Rickettsia, Shigella. MOTILE. *

PREVENT ACIDIFICATION- M. tuberculosis, L. pneumonophila.

PREVENT PHAGOLYSOSOME FUSION- Prevents phagosome fusing with lysosome and thus exposure to lysosomal enzymes. *M. tuberculosis, Salmonella, Brucella. *

SURVIVAL IN PHAGOLYSOSOME- eg. Coxiella burnetii (causes Q fever)