Kachur - Topic 3 - Adhesion and Invasion Flashcards
How do extracellular bacteria adhere to host cells
adherence allows bacteria to resist the mechanical clearing mechanism of the host
What are adhesions?
bacterial components that mediate interaction between the bacterium and the host cell surface
How do adhesins bind specifically to host cells
- host cells have molecules on surface co-opted by pathogens
- ## high degree of specificity b/w adhesion + host recognition site
What is a example of a receptor used for bacterial adhesins?
host surface glycans
What are the three types of pili?
- type I, F1 and type IV
What is the function of pili?
used for attachment to surfaces, other cells or bacteria
Where are pili found?
in both gram negative and gram positive bacteria
What are some pili characteristics
- fragile and constantly replaced therefore lots of opportunity
- pili can transition from swimming to surface-associated state that requires genetic changes to new surface state
- highly antigenic but heavily glycosylated to hide antigenic site
- allow velcro-like attachment to surfaces
What are type I pili?
rigid, long, and thin fragments that protrude off Gram negative bacteria
What is the unique feature of type I fili?
is that they induce hemagglutination (RBC aggregates)
What are type I pili made of?
composed of polymerized subunits of pilin protein
- length of pilus can range from 0.5uM to 10 uM
What is the chaperone/usher pathway?
assembles proteinaceous filaments on bacterial surfaces
- pili components are secreted by sec-transport pathway + chaperone usher pathway
these operons encode at least three minimum different proteins: chaperone, usher, and pilin
What is F1 pili?
shorter, linear, and flexible polymers that have a tendency to aggregate
Where is the F1 capsular antigen expressed?
expressed exclusively on Yersinia pestis
What are characteristics of F1 pili?
- antiphagocytic: prevents uptake by macrophages
- similar to type I/P pilus in that it uses CU system
What does the F1 capsule consist of?
tangle of thin, linear Caf1 fibers
- lots of variability (limited vaccine development)
- pilus is expressed @ 31 degrees but not 21 degrees
What are the different types of bacteria with type IV pili?
- EPEC
- Neisseria gonorrhoeae
- Neisseria meningtidis
How does binding of EPEC work?
- binding mode of bundling recognized LacNAc (N-acetylelactosamine) groups on host cells
- binding causes upregulation of virulence genes in bacterium and retraction of the pilus
What are characteristics of type IV pili?
- can retract while the pilus tip remains firmly adhered to the target surface leading to twitching motility
- in some bacteria, pilin is glycosylated
- in some bacterial species, such as EPEC and V. cholerae, type IV pili can aggregate laterally forming bundles
Pathogen profile: porphyromonas gingivalis (gram negative)
- microbial dybiosis on the teeth is facilitated by a shift in the microbiome towards Gram negative anaerobes
- keystone pathogen by production of a virulence factor called gingipain (cysteine protease)
- cleaves complement C5 protein into C5a which activates the C5a receptor and increases the inflammatory response but at the same time prevents microbial killing by leukocytes
- interesting - P. gingivalis does not need to be present i high number to initiate a disease state
What is twitching motility?
surface motility powered by the extension and retraction of type IV pili, which confers slow cell movement, often with a jerky or twitchy appearance
- motility seems to be required for virulence and may help engage the Type II secretion systems for the injection of toxins
What pili can bind DNA
type IV
Pathogen profile: Neisseria meningitides
- gram (-)ve bacterium; aka meningococcus
- exclusively human pathogen
- can cause meningitis and other forms of meningococcal disease
- about 10% of adults are carriers of the bacteria in their nasopharynx
- main cause of bacterial meningitis in children and young adults
- causes developmental impairment and death in about 10% of cases
How does DNA binding work in Neisseria meningitidis?
DNA transformation requires the presence of short DNA uptake sequences residing in coding regions of the donor DNA
DNA transferred often contains virulence genes including toxin resistance and antibiotic resistance
- fimbrae facilitate uptake of DNA = spreads virulence and causes resistance
How does meningoccocal type IV pili bind DNA
minor pilin ComP
- involved in natural competence that allows transformation
How does ComP work in Neisseria species?
- highly conserved
- only DNA sequence with homology (sequence similarity)
- will be integrated into genome
What are biofilms
dense, multiorganismal layers of bacterial communities attached to surfaces
- attachment to surfaces is mediated by an EPS - extracellular polysaccharide slime
- primary colonizers of biolfilms include Clostridia spp and Pseudomonas aeruginosa
Pathogen profile: Pseudomonas aeruginosa
- example of opportunistic pathogen
- primarily a nosocomial pathogen
- rod shaped, gram (-)ve, aerobic bacteria
- cause:
UTI, respiratory infections, GI infections
Why is pseudomonas aeruginosa such a opportunistic pathogen
natural habitat
- ubiquitous in soil + water
metabolism
- metabolically diverse: anerobic, aerobic
- can grow on 75 different organic substrates
nutritional requirements
- minimal nutritional needs: might not be reproducing; tolerant to more conditions
optimal growth temperature
- wide temperature range of 0-37 degrees
tolerance to physical conditions
- often grows in biofilms
- resistance to detergents + high salt
resistant to antibiotics + phagocytes
- antibiotic resistant genes have evolved
- associate with biofilms
What is the sortase enzyme
- catalyzes transpeptidation step of pilin synthesis
- important virulence factor or gram positive pathogens
- sortase enzymes are a group of prokaryotic enzymes that promote the covalent anchoring of surface proteins to the cell wall envelope to enable each microbe to effectively interact with its environment
What are the main functions of the sortase enzyme?
- cleave surface proteins + allow rearrangments + modifications
1) sorts protein of the cell surface + covalently links to cell wall
2) polymerizes pilin proteins: makes a sticky chain of adherance proteins
