WEEK 1 - bacteria adhesion (Human health+disease) Flashcards
attachment
specific interaction between bacterium and host
attachment
- on the bacterium
adhesion such as fimbriae/pili, surface proteins
attachment
- on the host cell
receptors such as host membrane glycoproteins, glycolipids, mucus
attachment
- colonisation
attachment to surfaces
invasion
entry to host cells
structure of gram positive pili
major pilin subunits are covalently linked
- long and stick out from surface
minor ancillary proteins are adhesins
pilus is anchored to the peptidoglycan (covalently)
pili are important in:
bacterial adhesion, colonization, biofilm formation, translocation across host membranes and invasion of host tissues
pilus assembly
subunits secreted through Sec
sortase enzyme recognises LPXTG motif
forms a covalent link tp:
a) pilin subunit
b) peptidoglycan
streptococcus pneumoniae
gram positive
main cause of community acquired pneumonia
also causes meningitis, bacteraemia, and infection of middle ear
readily colonise mucosal surfaces
adhesion of streptococci to cell surfaces
- pili interact with host cell or extracellular matrix
- Net negative charge –> need to break across repulsion to adhere –> long filaments are helpful to overcome this - zippering effect - bacteria brought closer to host (so can get more interaction)
- other adhesins on bacterial surface result in very close adhesion
- pilus - mediated bacterial aggregation
- microcolonies form on cell surface (more sophisicated than clumping, often in invasion form microcolonies prior to invasion)
gram positive pili overview
important in:
bacterial adhesion, colonization, biofilm formation, translocation across host membranes and invasion of host tissues
anchored to peptidoglycan
covalent linkage between subunits
example:
zippering in streptococcus
secretion is an important…
virulence mechanism
secretion
implies from the cytoplasm to the external environment
across both membranes in gram negatives
translocation
across a membrane
either cytoplasmic or outer membrane
three possible fates for secreted molecules
attached to the cell surface
released into the extracellular environment
injected directly into a host cell (effector proteins)
functions of secreted proteins
- cell shape and stability
- biogenesis of cell envelope - nutrient acquisition
- degradative enzymes - sensing/responding to environment
- motility
- flagella, pili etc - intercellular communication
- virulence factors
- exotoxins, effector proteins, protein adhesions
gram negative bacteria adhesion
- Neisseria gonorrhoeae
urogenital pathogen
cause of gonorrhoea (STD)
females
- mild vaginitis
- complications: pelvic inflammatory disease, sterility
males:
- painful infection of the urethral canal
architecture of the type 4 pilus
(gram negative)
flexible
central pore 1.2nm (structural phenomenon)
overall diameter 5-6nm
pilins have a highly conserved hydrophobic N-terminus
EPEC Neisseria gonorrhoeae
adhesion in Nesisseria
neisseria have type IV pilus and opacity-associated proteins (opa)
primary anchorage is via type IV pilus
type IV pili retract to bring bacteria closer to surface
tight secondary adherence opas bind to host cell receptors
twitching motility: N. gonorrhoeae
- role in pathogenesis
adhesion (brings other adhesins close to their target)
microcolony formation
mechanical force generated may have a role in signal transduction
twitching motility: N. gonorrhoeae
pilus is extended
- assembly ATPase
pilus attaches to host epithelium
- receptors
pilus is retracted causing movement
- retraction ATPase
- 1 um per sec
enteropathogenic E.coli (EPEC)
- overview
causes diarrhoea
colonises the gut epithelium
Type 4 pilus involved in the first stage of attachment
attaching and effacing lesions:
- effector proteins and intimin
- secretion via a T3SS
host cells from pedestals
- host actin cytoskeleton remodelled
EPEC pathogenesis
BFP (type 4 pilus) for attachment to enterocytes
adhesion via type 3 secretion system (T3SS)
T3SS injects “effectors” into the host cell
- including the receptor tir, becomes located in host cell membrane
- other effectors interact with host cytoskeleton proteins
pedestal formation
- Intimin (bacterial adhesin) binds to tir (receptor)
- cytoskeleton rearrangements ive rise to pedestal and loss of microvilli
