Bacterial pathogenesis

Question 1

Commensal

Answer 1

most microbes are never pathogenic

Question 2

Potential

Answer 2

many microbes are potentially pathogenic.

gain access to deeper tissues, immunocompromised patients

Question 3

Obligate

Answer 3

Very few microbes are always pathogenic. Entirely adapted to pathogenic lifestyle

Question 4

Key host-pathogen interactions

Answer 4

Bacterial diseases result from interactons with the host. Pathogens use ‘virulence factors’ to subvert or overpower host defenses, allowing access to nutrient rich environments

Question 5

Key events of host-pathogen interactions

Answer 5

Colonisation: invasion, stable adhesion to host surfaces, entry into host cells.
Multiplication: requires ability to evade or survive host defence mechanisms, allows local spread or dissemination to distal sites.
Transmission: to a new host, requires exit from the primary host
Damage: through these processes bacteria cause host damage, direct (toxins, invasion) or indirect (host response)

Question 6

Extracellular pathogens

Answer 6

Do not invade cells, but proliferate in the extracellular space

Question 7

Intracellular pathogens

Answer 7

Faculative pathogens invade host cells when it gives them selective advantage.
Obligate pathogens cannot live outside host cells

Question 8

Persisters

Answer 8

Persisters (bacterial), phenotypically drug tolerant, not resistant- associated with a state of dormancy
Persistent infections slow, but still progressing

Question 9

Dormancy

Answer 9

Pathogens enter a state of dormancy or non-replicating persistence, difficult to detect and to treat with standard drugs that target growth mechanisms

Question 10

Latency

Answer 10

Latent infections where the pathogen may not be demonstrable except when reactivation occurs

Question 11

How do bacteria colonise their hosts?

Answer 11

Motility- finding the right location. Chemotaxis, migration, usually by surface flagella
Adhesion- surface adhesins allow stable attachment to host cells or matrix. Can be assembled on the tip of long rigid pili
Invasion- entry into host cell or tissue. cell to cell spread
Replication- growth, host defence evasion, tissue destruction

Question 12

Characteristics of bacterial virulence factors

Answer 12

• Often specialised: not constitutively expressed, but regulated in response to the host environment. these characteristics do not apply to all virulence factors, nor to all pathogens
• genetic context: may be carried on extra- chromosomal plasmids or bacteriophage. may be grouped in ‘pathogenicity islands’ on chromosome.
• function: secreted onto the bacterial cell surface and/or into the surrounding environment. facilitate host interaction. host cell destruction. interfering with host cell functions

Question 13

biolfilms

Answer 13

Some bacteria establish complex biofilms on host tissues and inanimate surfaces. make infections difficult to eradicate by the immune system and antibiotics

Question 14

Adhesion

Answer 14

T3ss forms a translocon. effectors are trafficked into host via TL. Ec Tir inserts into host plasma membrane and interacts with Ec Intimin on bacterial surface. Promotes Tir clustering recruitment and remodelling of host actin formation of pedestals.

Question 15

Invasion

Answer 15

certain bacteria enter non-phagocytotic cells by specialised mechanisms.
Zipper mechanism- receptor mediated endocytosis
Trigger mechanism- bacterial proteins injected via T3SS

Question 16

Intracellular survival and replication

Answer 16

Other bacteria survive and replicate within intracellular vacuoles. but also survive in macrophages, allowing them to spread locally and throughout the body by the host defence system. inhibition of phago-lysosome fusion. Survive oxidative burst.

Question 17

Hostile environment

Answer 17

host sequesters essential iron, but pathogens bind iron at higher affinity than the host by secreting iron binding molecules and re-importing them. Acid in the stomach kills many pathogens, but some bacteria resist low pH by pumping H+ out of their cells.

Question 18

Macrophages

Answer 18

Pathogens may paralyse macrophages by subverting function. disruption of signalling and trafficking by injecting effector proteins into the host cell. Pathogens may resist phagocytosis by shielding with capsules- commonly made of polysaccharide

Question 19

Damage caused by bacteria

Answer 19

Direct- from bacterial action. Cytolysins: interact with host cell membranes. enzymatic degradation of membrane phospholipids, or pore formation.
Target cell lysis to disrupt host cell signal transduction, to disable immune cells

Question 20

Direct damage by enzymatic exotoxins

Answer 20

enzymatic intracellular toxins: poison host cells by specific catalytic activity. A-B toxins distinct receptor binding and intracellular active components. Single polypeptides cleaved to form active fragments, enter host cells by receptor-mediated endocytosis and/or retrograde transport. Blocks host translation

Question 21

Enzymatic cytotoxins

Answer 21

Target fundamental cellular functions e.g. Botulinium toxin prevents release of acetylcholine

Question 22

ADP-ribosylating enzymes

Answer 22

Cholera and perussis toxins target adenylate cyclase disturb cAMP levels, signal transduction and ion balance

Question 23

N-glycosiation

Answer 23

Blocks protein synthesis

Question 24

CLeave host SNAREs

Answer 24

cleave membrane fusion apparatus, disrupt neurotransmission

Question 25

What is retrograde transport?

Answer 25

The opposite way of protein transport pathway

Question 26

Indirect damage caused by host response

Answer 26

Acute inflammation- in response to sensing alarm signals
Chronic inflammation- relatively uncommon in bacterial disease, extended responses to persistent infection, ongoing tissue destruction, repair and inflammation

Question 27

protection against antibodies

Answer 27

Evade recognition- mimic or mask with host components, shut off or switch expression of surface proteins by phase variation, more complex DNA rearrangement mechanisms generate antigenic variation
Inactivate antibody- secretory antibody cleaved and inactivated by specific proteases of mucosal pathogens, bacteria bind and inactive antibodies directly

Question 28

Actin and pathogens

Answer 28

Many pathogens exploit host actin for their own purpose, to enter and to move within and between host cells