Adhesion and Invasion Flashcards
What is adherence essential for both extracellular and intracellular bacteria?
Extracellular: adherence allows bacteria to resist the mechanical clearing mechanisms of the host
Intracellular: pre-requisite for uptake or invasion
What are adhesions?
Bacterial components that mediate interaction between the bacterium and the host cell surface
How do adhesions bind to host cells?
They bind specifically to host cell surface receptors
There is a high degree of specificity between adhesion and the host recognition site
What are host surface glycans used for?
Receptors for bacterial adhesions as bacteria can specifically recognize and adhere to sugars
What are pili?
Fragile, hairlike adhesions that are frequently replaced and thus have a high potential for variation
How do pili hide their antigenic site?
The are highly glycosylated which allows for velcro-like attachment to surfaces
What are Type 1 pili and what Gram stain are they found on?
Rigid, long (0.5-10 micrograms), and thin filaments that protrude off Gram-negative bacteria
What is a unique feature of type 1 pili?
They induce hemagglutination
How are type 1 pili assembled and by which pathways?
Composed of polymerized subunits of the pilin protein = sec-transport pathway
Chaperone-usher pathway assembles proteinaceous filaments of bacterial surfaces
What do type 1 pili operons, at minimum, encode?
Chaperones, usher, and pilin
What are F1 pili?
Short, linear, and flexible polymers that have a tendency to aggregate
What are F1 capsular antigens exclusively expressed by and what is its function?
Y. pestis
Anti-phagocytic which prevents uptake by macrophages
What is a similarity between F1 pili and type 1 pili?
They both use the CU system
What does the F1 capsule consist of and what is its characteristic?
A tangle of thin, linear Caf1 fibers
Lots of variabilities = limited vaccine development
What are 3 examples of bacteria with type IV pili?
EPEC
N. gonorrhoeae
N. meningitidis
What does the binding of EPEC cause?
Upregulation of virulence genes in bacterium and retraction of the pilus
What do type IV fibers recognize?
Host cell sugars
What can EPEC and V. cholerae type IV pili do?
Aggregate laterally forming bundles
How does twitching motility work?
Surface motility powered by the extension and retraction of type IV pili, which confers slow cell movement that appears jerky
What is motility required for in type IV pili?
Required for virulence and may help engage the type II secretion systems for the injection of toxins
What is microbial dysbiosis on the teeth facilitated by?
A shift in the microbiome towards Gram-negative anaerobes
What is the keystone pathogen causing periodontal disease and is this pathogen alone sufficient to cause the disease?
P. gingivalis
It is not sufficient on its own but instead facilitates an ecological change to a disease state
How dos P. gingivalis act as a keystone pathogen?
By the production of a virulence factor called gingipain (cysteine protease)
How does gingipain work?
It cleaves complement C5 protein into C5a which activates the C5a receptor and increase the inflammatory response but at the same time prevents microbial killing by leukocytes
Which pili are the only ones that can bind DNA?
Type IV
What does DNA transformation from N. meningitidis require the presence of?
Short DNA uptake sequences residing in coding regions of the donor DNA
What does transferred DNA often contain?
Virulence genes including toxin resistance and antibiotic resistance
Where do meningococcal type IV pili bind DNA?
Through the minor pilin ComP which is a highly conserved component throughout Neisseria species
What do type IV pili promote?
The attachment to a variety of chemically diverse surfaces
What are biofilms?
Dense, multi organismal layers of bacterial communities attached to surfaces
What is the attachment of biofilms to surfaces mediated by?
Extracellular polysaccharide slime (EPS)
What are the primary colonizers of biofilms?
Clostridia spp and P. aeruginosa
What is P. aeruginosa and what does it cause?
A typically nosocomial, opportunistic pathogen
It causes UTIs, respiratory infections, and GI infections
What is the natural habitat of P. aeruginosa?
Ubiquitous in soil and water
What is the metabolism of P. aeruginosa like?
Metabolically diverse, can be aerobic or anaerobic
Can grow on 75 different organic substrates
What are the nutritional requirements of P. aeruginosa?
Minimal nutritional needs
What is the optimal growth temperature of P. aeruginosa?
Wide temperature range, 0-37 degrees
What is the tolerance of P. aeruginosa to physical conditions like?
Often grows in biofilms
Resistant to detergents and high salt
How is P. aeruginosa resistant to antibiotics and phagocytes?
Antibiotic-resistant genes have evolved
Association with biofilm
What does P. aeruginosa produce to adhere to the host or other surfaces?
Type IV pili
What is the process of biofilm formation?
Type IV pili produce EPS
Association with type IV pili with a substrate activates PSl genes which are involved in the formation of the biofilm
The early stages of biofilm formation have low levels of EPS and is reversible at this point
The accumulation of EPS causes a thick biofilm that allows for immune invasion and resistance to insults
What are PSl genes?
Polysaccharide synthesis locus genes
What do sortase enzymes do?
Catalyze the transpeptidation of pilin synthesis, linking of amino acids
What is an important virulence factor for Gram-positive bacteria?
Sortase enzymes
How are Gram-positive pili formed?
By covalent attachment of pilin subunits to each other and to the peptidoglycan layer
What do prokaryotic sortase enzymes 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 sortases?
Cleave surface proteins and allow rearrangements and modifications
Sorts proteins of the cell surface and covalently links to the cell wall
Polyermizes pilin proteins
What are the symptoms of diphtheria?
Sore throat
Grey patches in the throat
Barking cough
How many sortase enzymes does C. diphtheriae encode and how many does it actually need?
Encodes 6, only needs one
What is the purpose of SpaA?
Produces shaft of the pilus (type III)
What is SrtA?
The sortase that polymerizes pilus
What is SpaB?
Surface proteins
What is SpaC for?
Tip adhesion
What is the purpose of SrtF?
Housekeeping sortase that anchors pili into the cell wall
What system exports pilin proteins?
Sec transport system
How does S. aureus disguise itself?
Sortases function to attach immunoglobulins to the surface of the bacteria
Can mutants of SpaA cause infection?
No
What do non-pili adhesins facilitate?
Tighter binding of bacteria to host cells after initial binding by pili
What type of bacteria are non-pili adhesions common in?
Gram-positive food-borne pathogens
What is YadA and what does it promote?
A collagen-binding outer membrane protein that promotes cell adhesion to eukaryotic host and virulence
How does YadA protect bacteria?
Binding ECM
Temperature sensitive expression
Pro-phagocytic
Which bacteria is YadA found in?
Y. pestis
Y. pseudotuberculosis
Y. enterocolitica
What are 3 virulence factors of Yersinia?
LPS
YadA
Invasin
What is the difference between YadA and invasin?
YadA interacts indirectly with integrins though binding of the ECM
Invasin interacts directly with integrins
What do YadA and invasin trigger?
Entry into phagocytes as invasin zippers host membrane around it
What do many pathogens do once adhered?
Use the cell’s own cytoskeleton to invade the target cell either by triggering phagocytosis or by using the cytoskeleton to migrate through the cell
What are the main adhesins and receptors in Listeria?
Adhesions = internalin A (InlA) and internalin B (INlB)
Receptors = E-cadherin and Met
What are E-cadherin and Met components of?
Eukaryotic intracellular junctions
What exactly are InlA and InlB and what do they do?
Afimbrial adhesins
Necessary and sufficient to trigger host cell entry
What does the entry of L. monocytogenes into cells require?
Requires action polymerization and membrane remodeling
What does L. monocytogenes manipulate to its advantage?
Host-cell signaling and endocytic pathways
What do actin rearrangements due to the binding of listeria form?
Pseudopodia
What does listeria binding to the host cause and what does it facilitate?
Microfilament rearrangement and it facilitates phagocytosis
Where does listeria thrive?
In phagosomes
What does InlA induce?
Cytoskeletal rearrangements in the host cell for uptake of listeria by epithelial cells = virulence factor
What is E-cadherin and what binds to its extracellular domain?
Host protein
Transmembrane, cell-cell adhesion molecule
InlA binds to the extracellular domain
Assembly and attachment of what is central to intercellular adhesion and Listeria entry?
E-cadherin, alpha-catenin, beta-catenin
