Bacterial Pathogenesis, Survival, Processes, and Environmental Interactions

Question 1

How do commensal bacteria on our bodies protect against pathogens?

Answer 1

outcompete pathogens for nutrients
take up space
produce antimicrobial compounds

Colonisation of commensals in newborns acts as stimulus for immune system development

Question 2

What is an opportunistic pathogen?

Answer 2

an otherwise harmless bacteria that can cause infections in individuals w abnormal host defences
or when in the right conditions
eg commensals in our gut can be harmful if exposed in other places

Question 3

Name and define the different types of toxins produced by bacteria.

Answer 3

exotoxins: any toxin that is actively secreted by a bacterium in the environment or supernatant

endotoxin: a synonym for the LPS of gram-negative bacteria (cell-surface bound)

enterotoxin: an exotoxin that is effective in the gastrointestinal tract

Question 4

Why must bacteria sequester iron?

Answer 4

iron is an essential nutrient for most bacteria
limiting in host
sequestration is critical for in vivo success
performed by iron binding components called siderophores

Increased siderophores can lead to higher virulence as iron is needed for toxin production/gene regulation (or at least my notes say so 🐮)

Question 5

How does cholera cause disease?

Answer 5

attaches to ganglioside receptors in the gut
leads to mass amount of cAMP production which causes inhibition of reabsorption of Na and K as well as hypersecretion of Cl- ions

toxins don’t cause physical damage, purely chemical

Question 6

How does shigella cause disease?

Answer 6

able to bypass stomach as it encodes genes that allow it to overcome the acidic environment allowing it to reach the small gut

once it reaches it, releases toxins that cause pathological damage

taken up by microfold cells (m cells) in the small gut and cause them to apoptose

Can also disseminate from gut and cause damage in the CNS and kidney (also sepsis)

Question 7

What is a Type III Excretion System (T3SS)?

Answer 7

an injection system that forms a channel for toxins to enter from microbe into host
is a virulence factor
allows pathogenesis
Spans multiple membranes

Question 8

How is the genetic shift of Yersinia pestis (the cause of the bubonic plague) activated

Answer 8

temperature shift from flea to human

Question 9

What are some common themes of pathogenesis?

Answer 9

• breach of epithelial barrer
• proliferation intraphagosomally
• toxin release and delivery via T3SS
  evasion of immune system by alteration of LPS structure and delivery of effectors via T3SS

Question 10

What is the Sec pathway?

Answer 10

is used to export unfolded proteins in gram- bacteria
unfolded proteins move into periplasmic space where they are packaged by proteins in outer membranes

involves the proteins; SecA, SecYEG, SecB

Question 11

What is the TAT pathway?

Answer 11

is used to export folded proteins in gram- bacteria

3 components:
- Tat A: formation of membrane forming channel
- TatB: signal peptide binding
- TatC: signal peptide binding, recruits TatA

transported protein into periplasm or extracellularly by T2SS

Question 12

How does a Type I Secretion System work?

Answer 12

pulls membranes together allowing a channel to form
major efflux pump
Operates on proteins

Question 13

What is the role of a Type IV Secretion System?

Answer 13

moves genetic material between microbes

Question 14

What is a regulator?

Answer 14

usually a specific DNA binding protein that
binds in control region
Either stabilises RNA pol-promoter interaction (on) or competes for space with RNA pol (off)

Question 15

What is a regulon?

Answer 15

a group of genes controlled by a common regulator

Question 16

How many pathogens is enough to start an infection?

Answer 16

100
(Seems quite vague but whatever the lecture says ig 🐮)
(Wasn’t there another one that only took a few to cause disease - 🦑
(Probably 🐮)

Question 17

Dangers of commensals?

Answer 17

If displaced can cause infections

Antibiotic dysbiosis (Clostridium)

Can convert commonly ingested food substances into carcinogens

Immunocomprimised hosts

Question 18

What is the range of pathogenisis?

Answer 18

Pathogenic: can cause disease in individuals with normal host defences

Non-pathogenic: invade with no obvious detectable symptoms

Asymptomatic: detected by presence of organisms or antibodies raised against them

Latency: some organisms remain latent until activated with recurrence if symptoms

Opportunistic: can cause disease under specific conditions

Question 19

What is a commensal?

Answer 19

An organism found normally on parts of body that are exposed to or communicate with the external environment
(but da gut bacteria - 🦑)
(The gut is external 🐮)

Question 20

How can bacteria which are part of normal flora become pathogenic?

Answer 20

They acquire extra virulence factors (from plasmids)

Question 21

What can change the normal flora?

Answer 21

Changes in physiology during development

Antibiotics selecting for antibiotic resistant strains in body - overgrowth of said strain

New organisms acquired (eg newborn gains flora from maternal genital tract)

Question 22

Harmful effect of flora alteration by antibiotics?

Answer 22

Antibiotic use

Sensitive gut flora killed

Overgrowth of resistant flora, eg C. difficile

C. difficile toxin production

Diarrhoea, pseudomembraneous colitis

Question 23

What are Koch’s postulates?

Answer 23

Used to figure out if a given pathogen causes a specific disease

-Pathogen must be present in any case of the disease

-Pathogen must be isolated from diseased host and grown in pure culture

-Specific disease must be reproduced when pure culture is inoculated into healthy susceptible host

-pathogen must be recoverable from experimentally infected host

Question 24

What are fimbriae?

Answer 24

Adhesion structures on gram-negative bacteria
Made up of various protein subunits
Interact with eukaryotic cells/inert surfaces via receptors at tip (many of which recognise sugars)

Question 25

What are Pili?

Answer 25

Structurally similar to fimbriae, except longer
Most of the time only one is present on the surface
Involved in bacterial coniugation (F-pili), or act as receptors for phages (CTX phage in V. Cholerae)

Question 26

Purpose of Adhesins?

Answer 26

Adhering to host cells
Formation of colonies and biofilms

Question 27

Purpose of bacterial toxins?

Answer 27

One use is to destroy tissue

Question 28

Purpose of invasins?

Answer 28

Invading and multiplying in host cell

Question 29

How does Botulinum toxin work?

Answer 29

Clostridium botulinum releases toxin
Botulinum toxin acts at motor end plate to prevent acetylcholine release from vesicles
Causes lack of stimulus to muscle fibres -> irreversible relaxation and flaccid paralysis of muscles

Question 30

How does tetanus toxin work?

Answer 30

Clostridium tetani releases toxin
Toxin binds to inhibitory inter neurons and prevents the release of glycine (which under normal conditions acts on motor neurons to block excitation/release of acetylcholine)
Causes irreversible contraction, spastic paralysis

Question 31

What are invasion factors?

Answer 31

Exoenzymes used to invade host
Proteases, Glycosidases, Nucleases, Lipases
Also have toxins which work physically instead of enzymatically -insert into membrane instead

Question 32

Defensive pathogenicity factors?

Answer 32

Protect from host defence mechanisms
Negatively charged polysaccharide capsule (protect from phagocytosis and desiccation)
Slime
Biofilm (protects inner core from attack by immune system/antibiotics)

Question 33

Type II secretion system?

Answer 33

Moves protein into the periplasm via the sec and TAT systems

Question 34

How does the body tell pathogenic and commensal E. Coli apart?

Answer 34

T3SS present only in pathogenic (used for translocation of effector molecules) is sensed by intestinal cells (T3SS also trigger immune response)

Commensals don’t have the genes encoding T3SS or toxins
Therefore genomic variation dictates host-pathogen interactions

Question 35

What is the arn operon?

Answer 35

Controlled by PhoPQ TCS
Alters bacteria’s LPS so they can’t be sensed by the host immune system (immune evasion)
Also encodes resistance to anti microbial molecules released by innate cells

Question 36

Quorum sensing?

Answer 36

Gram negative release Acyl-homoserine lactones
Gram positive release Autoinducing peptides
(Produced by QS signal synthases)
More bacteria = higher QS molecule concentration
Sensed by TCS, cause changes in gene expression at a certain threshold of bacteria
(Eg turning on virulence genes when a sufficient amount of bacteria to overwhelm immune system is present)