Mechanisms of host-pathogen interactions L9 Flashcards
how can host-microbe interactions be measured
qualitative
- species can be defined as pathogenic
quantitative
- clinical isolates can be distinguished between by the degree of damage (virulence) they cause
define pathogenicity/ virulence factors
structures, molecules or regulatory systems that enable the disease process
what are microbes aim
to colonies niches
- do this in similar , generalisable ways
what is pathogenicity driven by
adhesion of microbe to epithelial surface or invasion of underlying tissue
what must microbe do in order to become a pathogen
Must breach microbial (microbiome forming colonisation resistance), immunological and physical barriers
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
- Adherence to mucosal surfaces
- capsule
- biofilms
4.fimbrial - protein secretion
- toxins
- pathogenicity islands
describe Adherence to mucosal surfaces
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)
give the process of adhering to mucus causing disease
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
describe the two types of adherence and give examples
- specific: V. cholerae
- specific proteins on bacterial surface interact with specific receptors on the host cell - 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
describe the bacterial capsule
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
how do biofilms form after bacteria have adhered
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
what are the advantages of biofilms for bacteria
Physical defence (immune cells, antibiotics)
Nutrition
Intercellular communication
Exchange of genetic material
Helps maintain a favourable “niche
what are Fimbrial
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
what are the advantages of fimbriae
Type 1 fimbriae:
- CUP type adhesin
- Found widely in Gram –ves
- FimH has a specifc affinity for mannose – key to bladder colonisation by UPEC!
describe Fimbrial catch-bond theory
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
what are the two ways of transport across the inner membrane for bacterial proteins
- SEC: unfolded protein, common
- TAT: folded, exclusive substrate
what does SEC allow
insertion of proteins into the inner membrane
describe the 2 step protein secretory system in gram negative
Two step systems in Gram negatives typically follow SEC translocation to the periplasm followed by a specific system for OM transport
give 5 examples of secretory systems
- 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!!! - T4SS
- primarily involved in genetic exchange (conjugation) - 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
what do bacterial toxins do to host
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
describe the two types of bacterial toxins
- Exotoxins
- specifically secreted protein toxins - Endotoxins
- ones inside bacteria itself- inherent proteries, promote infections in non specific ways
give two examples of exotoxins and where they are encoded
Stx and Ctx
- encoded on PAIs
what are the Different mechanisms of action for exotoxins
Cytolytic (hemolysin, alpha-toxin)
Disruptive (AB toxins)
Stimulatory (superantigens)
give different types of exotoxins and what they effect
Enterotoxins affect the small intestine resulting in fluid loss (Ctx)
Neurotoxins of nerve cells (Tetanus and Botulinum)
Renal toxins (Stx)
- they are site specific
