Virulence Factors Flashcards
Streptococcus Pneumoniae
Polysaccharide capsule Pneumolysin Hyaluronidase Neuraminidase Pili Lipoproteins Peptidoglycan adn teichoic acids Choline-binding proteins competence protein Autolysin
Polysaccharide capsule
most important virulence factor for S. pneumoniae
antiphagocytic (except when anti-capsule antibodies…opsonic)
> 80 capsular types, can be identified by Quellung rxn.
most pneumonias are caused by 23 of the 80 types
Pneumolysin
pore-forming toxins (hemolysins)
binds cholesterol in host cell membranes–>pore–>cell lysis
Infection of lungs: recruits neutrophils and lymphocytes= more inflammation; interacts w/ TLR4–>stimulates cytokine production
Infection of meninges: especially bad if bacteriolytic antibiotics are used
breaks down hemoglobin into green pigment–>alpha hemolysis
Hyaluronidase
aids spread of bacteria in hyaluronic acid tissues
Neuraminidase
clips N-acetylneuraminic acid from cell surface glycoproteins
may 1) cause direct damage, or
2) unmask binding sites for pneumococci
loss of neuraminic acid=spread of pneumococci along Eustachian tube towards middle ear
Pili
LPXTG-sortase mechanism–>polymer of pilus protein monomers
adhesion to epithelial cells
Lipoproteins
cell surface molecules important in various ways
i.e. iron uptake
Peptidoglycan and teichoic acids
main cell wall components
Wall teichoic acid
lipoteichoic acid
C-Polysaccharide
Also stimulate inflammation b/c recognized by pathogen recognition receptors (i.e. TLRs)–> cytokine secretion
Wall teichoic acid (WTA)
long polyglycerolphosphate moity covalently bound to peptidoglcan petide crossbridges
very negatively charged molecule
Lipoteichoic acid (LTA)
polyglycerolphosphate moity bound in different way
diacylglycerol moity on one end and two fatty acids intercalated into membrane
negativity of LTA and WTA neutrolyzed by linking choline instead of D-alanine
C–polysaccharide
teichoic acid and adherent fragments of peptidoglycan
bound by CRP–>complement activated–> inflammation
choline-binding proteins (CBPs)
up to 10
anchored tto cell surface via repeat domains that bind to choline in cell wall
1) several are hydrolytic enzymes involved in virulence through release of cell wall fragments that stimulate inflammation (i.e. LytA)
2) Others bind to nasopharyngeal or lung epithelium (i.e. PsaA)
3) PspA and PspC inhibit phagocytosis by binding complement factor H
4) Binding to polymeric immunoglobulin receptor aids in transepithelial transport necessary for deep tissue invasion
5) Adhesion to platelet-activating factor receptor important in invasion of CNS
Competence protein
enables pneumococci to acquire DNA from environment
Autolysin, LytA
disrupt cell wall formation
important in cell wall remodeling during cell division
can also cause bacteria to lyse–> release of cell wall fragments–> activation of immune system
