Mechanisms of host-pathogen interactions L9

Question 1

how can host-microbe interactions be measured

Answer 1

qualitative
- species can be defined as pathogenic
quantitative
- clinical isolates can be distinguished between by the degree of damage (virulence) they cause

Question 2

define pathogenicity/ virulence factors

Answer 2

structures, molecules or regulatory systems that enable the disease process

Question 3

what are microbes aim

Answer 3

to colonies niches
- do this in similar , generalisable ways

Question 4

what is pathogenicity driven by

Answer 4

adhesion of microbe to epithelial surface or invasion of underlying tissue

Question 5

what must microbe do in order to become a pathogen

Answer 5

Must breach microbial (microbiome forming colonisation resistance), immunological and physical barriers

Question 6

there are many more bacteria in microbiome than pathogens
- would think bacteria would outcompete pathogens due to their large number
- however, pathogens still cause damage
- how

Answer 6

1. Adherence to mucosal surfaces
2. capsule
3. biofilms
   4.fimbrial
4. protein secretion
5. toxins
6. pathogenicity islands

Question 7

describe Adherence to mucosal surfaces

Answer 7

mucosal surfaces line common infection sites e.g gut, lungs
pathogens use mechanisms to adhere to mucus which either subverts host cell function (extracellular) or invade underlying tissue (invasive)

Question 8

give the process of adhering to mucus causing disease

Answer 8

pathogen adheres to mucus
pathogen invades via epithelium
pathogen colonises and grows producing virulence factors
causes toxins to have an effect
or pathogens continue growing at further sites
results in tissue damage and disease

Question 9

describe the two types of adherence and give examples

Answer 9

1. specific: V. cholerae
   - specific proteins on bacterial surface interact with specific receptors on the host cell
2. non-specific: E. coli
   - has a polysaccharide capsule that acts as physically barrier to decimation systems, helps to avoid triggering immune response and helps to adhere

Question 10

describe the bacterial capsule

Answer 10

a polymer made from sugar units- polysaccharide
normally encases gram negative bacteria
providing resistance from immune recognition, phagocytosis and complement killing and helps in biofilm formation.
some bacteria have multiprotein complexes that cause pores in bacteria surface resulting in lysis
- if have a capsule, they are more resistant to this

Question 11

how do biofilms form after bacteria have adhered

Answer 11

3D communities encased in sugar matrix
cell surface appendages on bacteria cause adherence to
- Host tissues, Medical devices such as catheters, Abiotic surfaces in industry
capsules help as they are sticky
colonisation then happens
- bacteria grow and polysaccharides form
- even more growth forming biofilms
Can be formed of multiple, symbiotic bacterial species living in parallel
Likely the default mode of growth for bacteria in nature

Question 12

what are the advantages of biofilms for bacteria

Answer 12

Physical defence (immune cells, antibiotics)
Nutrition
Intercellular communication
Exchange of genetic material
Helps maintain a favourable “niche

Question 13

what are Fimbrial

Answer 13

filamentous, cell surface protein structures
Capped by sugar binding, lectin-like proteins
Similar structures called Pili are longer, less abundant and involved in genetic exchange
e.g type 4 pili

Question 14

what are the advantages of fimbriae

Answer 14

Type 1 fimbriae:
- CUP type adhesin
- Found widely in Gram –ves
- FimH has a specifc affinity for mannose – key to bladder colonisation by UPEC!

Question 15

describe Fimbrial catch-bond theory

Answer 15

when there is high stress on bacteria with type 1 fimbriae, the fimbriae form tight interaction with receptors on host.
Strength of binding dictated by an allosteric switch in the FimH-sugar interaction
- harsh environments improve attachment of bacteria this way

Question 16

what are the two ways of transport across the inner membrane for bacterial proteins

Answer 16

1. SEC: unfolded protein, common
2. TAT: folded, exclusive substrate

Question 17

what does SEC allow

Answer 17

insertion of proteins into the inner membrane

Question 18

describe the 2 step protein secretory system in gram negative

Answer 18

Two step systems in Gram negatives typically follow SEC translocation to the periplasm followed by a specific system for OM transport

Question 19

give 5 examples of secretory systems

Answer 19

1. Type 2 secretory system:
   - inner membrane base plate and needle forming pore in host cell membrane- need ATP to transport proteins
   - required for epithelial attachment (EHEC) and in some cases invasion (Salmonella). NOT receptor specific!!!
2. T4SS
   - primarily involved in genetic exchange (conjugation)
3. T6SS
   - Used for inter-bacterial warfare as well as host-cell subversion
   - like a pump- used to kill other bacteria
   Expression of type 3 and 6 is determined by environment- nutrients, pH, other bacteria

Question 20

what do bacterial toxins do to host

Answer 20

Cause damage to host tissue/cells

Damage is typically distal to the site of infection

Toxins offer a range of advantages such as access to tissue and nutrients, facilitating transmission and in some cases enhancing other virulence processes

Question 21

describe the two types of bacterial toxins

Answer 21

1. Exotoxins
   - specifically secreted protein toxins
2. Endotoxins
   - ones inside bacteria itself- inherent proteries, promote infections in non specific ways

Question 22

give two examples of exotoxins and where they are encoded

Answer 22

Stx and Ctx
- encoded on PAIs

Question 23

what are the Different mechanisms of action for exotoxins

Answer 23

Cytolytic (hemolysin, alpha-toxin)
Disruptive (AB toxins)
Stimulatory (superantigens)

Question 24

give different types of exotoxins and what they effect

Answer 24

Enterotoxins affect the small intestine resulting in fluid loss (Ctx)
Neurotoxins of nerve cells (Tetanus and Botulinum)
Renal toxins (Stx)
- they are site specific

Question 25

why may Stx toxin not be beneficial

Answer 25

triggered in response to certain stresses
inhibits T3SS
-T3SS needed for colonisation
- needle that injects toxin and proteins
stx stimulates cell receptor expression in host
maybe first few inhibit T3SS but stimulate cell receptor so later bacteria can adhere better

Question 26

what are endotoxins and what do they cause

Answer 26

Cell bound lipopolysaccharides of Gram negative bacteria

Only released when cells lyse

Release can induce fever, tissue inflammation and diarrhoea

However, far less toxic than exotoxins

Question 27

Pathogenicity islands (PAIs)

Answer 27

islands of DNA that pathogenic bacteria have but non-pathogenic bacteria do not
transfer of these islands mediated by phage’s
Excess genetic material provides an ecological selective advantage

Question 28

give example of PAIs

Answer 28

UPEC and EHEC

Question 29

give significance of PAIs in UPEC

Answer 29

Strains often contain 100’s of excess bases
PAIs often encode diverse virulence factors
Can act as genetic signatures for highly pathogenic strains

Question 30

give significance of PAIs in EHEC

Answer 30

EHEC specific O-islands account for 1.56 Mb of DNA (~26% of the genome)

LEE-encoded T3SS is essential for its pathogenesis

Many cryptic prophages encode effectors of the T3SS (>30)

Stx toxin also encoded on a cryptic prophage – ecological benefit?

Question 31

what are the two types of salmonella that differ in their genomes

Answer 31

Salmonella genomes differ largely between generalist enteric Typhimurium strains and human-restricted Typhi strains (only pathogenic in humans)
- S. Typhi contain overlapping PAIs but many contain InDels/MUTATIONS and pseudogenes, owing to the host restricted nature of the pathogen
- loose DNA