10. bacteria pathogenicity

Question 1

2 groups of successful bacterial pathogens

what do they both contain

Answer 1

1. opportunistic pathogens

only cause disease when host defences impaired

2. primary pathogens

capable of causing disease in absence of immune defects

both have virulence determinants

rarely a single virulence can make it pathogenic

virulence is multifactorial

Question 2

what is important in virulence

Answer 2

bacterial surface

• mediates initial reaction

Question 3

infection and diseae

Answer 3

infection: persistence without necessarily causing tissue damage
disease: damage to host

Question 4

bacterial disease processes

Answer 4

1. Colonisation - adhesion
   - nutrient acquisition
2. Invasion of tissues
3. Avoidance of host defences
4. Tissue damage
5. Transmission

Question 5

colonisation

Answer 5

Establishment of a stable population of bacteria in the host

Source of bacteria: environment, infected individuals or our own normal flora

Frequently first interaction occurs on a mucosal surface e.g respiratory tract, gastrointestinal tract or urogenital tract

Question 6

mucosal surfaces function

how do bacteria overcome the protective function of mucus

Answer 6

Mucus forms a protective barrier and involved in normal physiological flushing mechanisms e.g saliva in the mouth, peristalsis in the gut

To overcome these flushing mechanisms and persist, bacteria must adhere to mucosal surfaces

Some bacteria adhere to other surfaces

e.g streptococci to tooth surfaces staphylococci to plastic catheters, implants etc

Question 7

adherance

two stages

what can subsequent stages result in?

Answer 7

1st stage - Association - involves non-specific forces e.g charge and hydrophobicity – weak and reversible

2nd stage - Adhesion - involves specific binding betweeen bacterial adhesins and host receptors – strong interactions and non-reversible

Subsequent stages may result in aggregation to produce a biofilm on a surface.

Biofilms may contribute to chronic infections and may be difficult to treat with antibiotics

Question 8

bacterial and host cell adhesins

Answer 8

Bacterial: Fimbriae/pili - rod like protein adhesins e.g E. coli

Polysaccharide adhesins e.g oral streptococci

Host receptors include:

Blood group antigens

Extracellular matrix proteins e.g fibronectin, collagen

Question 9

NUTRIENT ACQUISITION

which nutrient is important

how does bacteria acquire this

Answer 9

iron uptake

Iron is essential for bacterial growth

In tissues free iron levels are below that required to support bacterial growth

bacteria express high affinity iron uptake systems

2 main systems:

1. Siderophores
2. Direct binding of iron transport proteins

Question 10

nutrient acquisition by siderophore

Answer 10

Question 11

nutrient acquisition by direct binding of iron transport proteins

Answer 11

Question 12

invasion

what can structures bacteria invade

what is needed to help in invasion

Answer 12

Once established in the body, some bacteria are able to penetrate into, through or between cells.

This Invasion process may aid in survival and their spread to other body sites

e.g Neisseria meningitidis spread from nasopharynx to the bloodstream or meninges

Some bacteria can invade epithelial cells

Others invade phagocytic cells (macrophages)

Adhesion to specific receptors usually the first stage in invasion - adhesins called invasins

Question 13

what are some of the host defences that bacteria must avoid

Answer 13

Complement- kills many Gram-negative bacteria

Complement and antibodies oposonize bacteria, promoting phagocytosis and killing by polymorphonuclear leukocytes (PMNs) and macrophages

Cytokines modulate both antibody and phagocytic responses

Question 14

avoidance of complement

bacterial features that avoid

Answer 14

1. LPS on gram negative bacteria causing sepsis are complement resistant

Polysaccharide side chains of LPS sterically hinder access of activated complement components to the bacterial membrane

2. Capsules can interfere with complement binding e.g E. coli

3. Surface proteins inhibit binding of complement to the bacterial surface e.g M proteins in Streptococcus pyogenes

•Staphylococcus aureus produces factors that interfere with complement activation

Question 15

avoidance of anitbody actions

Answer 15

capsules prevent antibody binding or are weakly antigeni- prevent opsonization and phagocytosis

Many different capsular types may be produced

Antigenic variation is used by some bacteria to avoid binding of antibodies e.g pili variation in N.gonorrhoeae

IgA protease degrades IgA on mucosal surfaces and prevents bacterial aggregation and clearance

S.aureus protein A binds the Fc region of IgG and inhibits opsonisation

Question 16

avoidance of phagocytosis

Answer 16

toxins produced: kill phagocytes or inhibit migration to sites of infection

e.g S. aureus a-toxin

capsules inhibit phagocytosis e.g Haemophilus influenzae

pathways involved in intracellular killing within phagocytes inhibited e.g Mycobacterium tuberculosis

Question 17

modulation of cytokine responses

Answer 17

Some bacteria can modify normal cytokine responses and alter the immune response in favour of bacterial survival

e.g Staphylococcus aureus

Question 18

how can tissue damage occur

Answer 18

1. Direct effects of bacterial toxins
2. Indirect effects of bacterial toxins
3. Induction of autoimmune responses

Question 19

bacterial toxins

Answer 19

1. Exotoxins - actions selective for specific biochemical targets e.g protein synthesis -Diphtheria toxin

2. Endotoxin (LPS) - activates many biochemical pathways - effects mediated by triggering of cytokine release from mammalian cells Cytokines released include TNF -a

Question 20

exotoxins vs endotoxins

Answer 20

Question 21

structure of LPS

Answer 21

Question 22

exotoxins

Answer 22

classified into specific mode of action

Tetanus toxin - interferes with synapse function

Diphtheria toxin - inhibits mammalian protein synthesis