Staph Aureus Flashcards
Staphlococcus aureus
how many virulence factors?
what can it cause?
due to things like what?
200-300 virulence factors
food poisoning, dermal infections of bone and joint, sinus, blood and skin
carriers, biofilms, facultative intracellular pathogen, fate depends on host response, isolate and genotype
toxins that induce host cell lysis: (3)
alpha-toxin
phenol-soluble modulins (PSM)
panton-valentine leukocidin (PVL)
secreted factors that inhibit neutrophil recruitment: (2)
- chemotaxis inhibitory protein of staphylococci (CHIPS)
- extracellular adherence protein (Eap)
factors that inhibit reactive oxygen species: (2)
- golden caretenoid pigment
- superoxide dismutase enzymes
FnBPA and FnBPB=
Fibrionectin binding proteins A and B
-epithelial, endothelial, fibroblasts, osteoclasts, keratinocytes and cellular surface proteins Hsp60 and Hsp70
Teichoic acids-
Zipper mechanism-
Kinases are?
teichoic acids in cell wall (WCT) and nasal colonization
Zipper mechanism- formation of actin cups
Kinases are host cell specific
MAPK=
P13K=
ERK=
mitogen-activated
phosphoinositide
extracellular regulated
1) extended phagocytic existence=
2) evasion of phagocytic lysis (lysosome)=
1) up regulation of anti-apoptotic factors
2) by disintegration of the lysosome membrane by alpha-toxin A, among other strategies.
Staph aureus is phagocytosed by? which leads to?
bacterium resists the action of reactive oxygen intermediates by?
S. aureus is phagocytosed by a neutrophil, the neutrophil is activated, and the bacterium is contained within a phagosome, where it encounters multiple antibacterial host defenses.
secreting superoxide dismutases (SODs), which dismutates O2- to O2, and inactivates radicals.
Reactive nitrogen intermediates are resisted by?
resistance to lysozyme is provided by?
resistance to cationic antimicrobial peptides is mediated by?
resisted by an inducible lactate dehydrogenase (iLDH) that is insensitive to the intermediates, allowing respiration to continue.
lysozyme resistance is provided by modifications to the muramic acid in peptidogylcan, this altering the cell wall.
is mediated by secretion of staphylokinase and aureolysin, which bind to the cationic peptides, by efflux pumps that remove the peptides from the cell, and by modifications in the cell wall that increase its positive charge, thereby decreasing the affinity of the positively charged antimicrobial peptides for the bacterium.
Bovine mastitis strains (sphingomyelinase)=
Beta-toxin in a minority of human strains, which selectively kills monocytes and destroys platelets.
Survival in the face of phagocytosis
dependent on?
log vs lag and stationary phases?
phagosomal acidification=
dependent on MOI (multiplicity of infection) and growth phase of the bacteria
Log phase vs lag and stationary phase; it is safer for the bacteria to be in lag or stationary phase because they do not produce any compounds which would “give” them away.
Phagosomal acidification (production of hypochorous acid HOCl) of rapidly-growing bacteria more efficient.
Acidification and digestion by the phagocyte is required for MyD88-dependent TLR responses to infection
not all bacteria are disinfected by phagolysosomes, stuff that keep it alive: (8)
1) persistence: attricuted to small colony variants (SVCs) metabolically quiescent
2) non-hemolytic
3) non-pigmented
4) reversible auxotrophy (heme and ocidative phosphorylation pathways)
5) deficiencies with quorum sensing-controlled virulence
6) thicker cell wall
7) improved stress responses
8) mutants in the accessory gene regulator locus (agr)
agr dependency-
alpha-toxin-
delta-toxin-
lyses-
activity similar to?
dependent on?
accessory gene locus
alpha-toxin facilitates translocation into the cytoplasm
delta-toxin is encoded by the agr-effector RNA III and is translated approx 1 hour after transcription
lyses a variety of organelles
activity and mode of action simlar to nonionic detergents
dependent on presence of sphingomyelinase beta-toxin
alternative factors: (4)
1) lipases
2) phenol-soluble modulins (PSM)
3) delta-toxin is a PSM, other incl. PSM-alpha and PSM-beta
4) part of the agr system and quorum-sensing system
molecular patterns of pathogens are detected by?
PG casues?
alpha-toxin interferes with?
molecular patterns of pathogens are detected by NOD proteins (that detect CW components, NOD1 and NOD2) of host cells.
PG causes a conformational change in NOD proteins, leads to NFKB and inflammation
alpha-toxin interferes with NOD2 and phagosomal membrane integrity
PCD-
location?
proteins?
panton-valentine leokocidin
mitochondrial localization
Bax and Bcl proteins/ pro and anti apoptotic proteins
For Bax-independent PCD, alpha-toxin and PVL cause?
Bcl overexpressing cells were protected from?
alpha-toxin and PVL cause caspase activation via pore formation, leakage of cytochrome C
Bcl overexpressing cells were protected from alpha-toxin mediated cell death
CHIPS are?
complement labels bacteria with?
bacterial human pathogens have evolved differents strategies to impair?
Chemotaxis inhibitory protein of staphylococcus aureus (CHIPS)
the plasma proteins of the complement system are essential in the innate immune response against bacteria.
complement labels bacteria with opsonins to support phagocytosis and generates chemoattractants to attract phagocytes to the site of infection.
impair the complement response
FPRs=
PRRs are used as?
these molecules known as?
FPRs= formylated peptide receptors
PRRs are used as microbial sensors to detect a set of enoltionarily conserved molevules found in a variety of pathogens.
these molecules known as PAMPs (pathogen associated molecular patterns) which do not cause disease but are the major external stimulator of inflammatory response
CHIPS are a?
a potent inhibitor of?
their target cells by
CHIPS are exoprotein produced by several strains of S. aureus
potent inhibitor of neutrophil and monocyte chemotaxis towards C5a and formylated peptides
these chemoattractants act on their target cells by binding and activating the C5aR and formylated peptide receptor (FPR)
CHIPS could be promising for?
leading to development of a new anti-inflammatory compound for diseases in which damage by neutrophils plays a key role.
Eap=
facilitate?
also been shown to?
Eap= extracellular adherence protein, responsible for imparied wound healing
wide range of protein, protein interactions that facilitate the initiation and dissemination of staphylococcal disease
also shown to interfere directly with complex, signaling-dependent events such as leukocyte recruitment
Eap interacts with
interactions of Eap with epithelial and endothelial cells, fibroblasts and the extracellular matrix (ECM)
golden carotenoid pigment
impairs?
impairs neutrophil killing and promotes virulence through its antioxidant activity
overview of oxidative and nitrosative stressors and their potential targets
metal ion homestasis: (3)
Stress response: (4)
1) iron
2) manganese
3) copper
1) metabolic regulation
2) general stress response
3) stringent response
4) SOS response
Virulence: (3)
Metaolic response: (3)
1) exoproteins
2) cell surface proteins
3) antibiotic resistance
1) metabolite pool
2) redox status
3) energy status
mutants lacking the pigment are?
less virulent
protective vaccines should be able to elicit three major immune responses:
1) ABs to directly inhibit bacterial viability and/or toxicity
2) ABs to mediate epsonophagocytosis
3) cell-mediated immunity to stimulate recruitment of phagocytes at the site of the infection
