Bacterial Virulence Mechanisms Flashcards
host-pathogen relationship
*dynamic relationship, each modifying the activities and functions of the other
*outcome is dependent on:
-virulence of the pathogen
-relative degree of susceptibility or resistance of the host
pathogenesis
ability of an agent of infection to produce disease
virulence
an agent of infection’s degree of pathogenicity
*how effectively it causes the disease
*the severity of the disease
virulence mechanisms
genetic or biochemical features which allow an organism to produce disease
pathogens must be able to accomplish the 5 requirements for infection:
- entry
- colonization
- immune evasion
- propagation
- transmission
portals of entry for pathogens
*mucus membranes
*skin
*parenteral (needles, bites, maternal-neonatal)
LD50
lethal dose required to kill 50% of experimentally inoculated test animals
ID50
infectious dose required to cause disease in 50% of inoculated test animals
which pathogen has a very HIGH ID50
vibrio cholera
(requires a lot of vibrio to become infected)
what pathogen has a really LOW ID50
shigella
(does not require very much shigella to become infected)
quorum sensing
*organisms sense and respond to their environment (produce, release, and sense extracellular signals to regulate gene expression)
*cell-to-cell communication
quorum sensing in gram NEGATIVE bacteria
*use acyl-homoserine lactones (AHL’s)
*diffuse freely through bacterial membrane
quorum sensing in gram POSITIVE bacteria
*use processed oligo-peptides
*two-component system: membrane-bound sensor kinase receptors and cytoplasmic transcription factors that direct gene expression
pathogenicity islands
*virulence genes in CLUSTERS (present in pathogens, absent in benign relatives)
*pick up genes from environmental gene pool by horizontal transfer
*large, distinct chromosomal regions
colonization by an organism
*the initial establishment of an organism within a particular habitat or of a colony at a particular site
*usually colonize sites that connect to the external environment
*often requires:
-IgA protease
-motility
-adherence
-biofilm production
IgA protease
-secretory IgA is the principal immunologic defense of respiratory and other mucosal surfaces in the body
***IgA protease causes LYSIS of IgA, allowing adherence of the organism to the mucus membrane
flagella
*motility
*can function as adhesins
*flagellin or FliC, filament forming component of bacterial flagella
type IV pili
*filaments at the poles of bacilli
*allow for gliding motility along a solid surface
*pili are extended and attach to a surface and then retract (causing a twitching motility) or can slingshot
examples of adhesins (virulence factors)
fimbria/pili & MSCRAMMS
fimbria
*adhesive hair-like structures extending from surface
*usually binds to a specific sugar on the cell surface (the adhesin in LECTIN)
P fimbria in E. coli
*virulence factor found in a pathogenicity island of uropathogenic E. coli
*binds to Gal-Gal on uroepithelial cells
*this is the most common cause of UTIs in the world
MSCRAMMs (microbial surface components recognizing adhesive matrix molecules)
*proteins that bind components of the ECM of epithelial cells, such as fibronectin, collagen, or laminin
*secreted by staph, strep, and others
biofilms
*irreversibly attach to a surface and produce extracellular polymers (matrix formation)
*provides antimicrobial resistance
*ALL bacteria CAN form biofilms, but some are really good at it
type III secretion systems (T3SSs)
*complex bacterial structures in gram NEGATIVE pathogens for injecting effector proteins directly into the host cell
*effector proteins commonly interfere with host cell cytoskeleton to promote attachment and invasion, create cytotoxicity and barrier dysfunction, and block immune system
T3SS apparatus
*consists of rings that provide a tube across the inner and outer bacterial membranes, including the peptidoglycan layer
*needle-like structure extends from outer membrane ring and projects from the bacterial surface (effector proteins transported through the hollow “center” of the needle)
type IV secretion systems (T4SSs) - subfamilies
2 subfamilies:
1) conjugation systems (mediate interbacterial DNA transfer)
2) effector translocators (used by gram - for delivery of virulence proteins)
what pathogen has a T4SS
H. pylori
invasins
enzymes that promote invasion, including:
-hyaluronidase
-streptokinase
-collagenase
what is invasion by an organism affected by
*colonization
*production of invasins
*ability to evade host defenses
*blocking of phagocytosis
examples of enzymes that help an organism evade host defenses
-leukocidins
-hemolysins
-coagulase
leukocidins
*kill WBCs; releases and ruptures lysosomes
*can create more tissue damage
hemolysins
*cause lysis of RBCs
*alpha or beta hemolysis
coagulase
stimulates clotting to protect bacteria from phagocytosis
collagenase
*breaks down collagen (connective tissue)
*RAPID SPREAD through tissue
hyaluronidase
*breaks down hyaluronic acid (connective tissue)
*“spreading factor”
how can organisms survive host defenses
*antiphagocytic factors (kill phagocytes or facilitate avoidance of phagocytes)
*kill the leukocyte (using leukocidins)
*intracellular survival (readily engulfed but capable of surviving internally)
capsule - anti-phagocytic virulence factor
*polysaccharide layer outside the cell envelope
*found in both Gram + and -
*resists phagocytosis
protein A
*protein on cell wall of Staph aureus
*impairs phagocytosis by binding the Fc portion of antibodies
*staph with protein A is more likely to be a colonizer of the nose
M protein
*produced by some species of strep
*messes up complement by binding to factor H, destroying C3-convertase and preventing opsonization, therefore STRONGLY ANTI-PHAGOCYTIC
*our cells can generate antibodies against M protein
siderophores
iron chelators that are excreted into the environment, bind iron, and then re-enter the cell
*iron is very important for bacteria
bacteriocins
toxins produced by bacteria to inhibit growth of related strains
toxins
bacterial products that directly harm tissue or trigger destructive biological activities
exotoxins
*generated by certain species of gram pos or neg
*ACTIVELY SECRETED
*each toxin has a specific action
*generally does NOT produce fever
*heat labile (inactivated at high temps)
types of exotoxins
-cytotoxins: kill cells
-neurotoxins: interfere with normal nerve impulses
-enterotoxins: cause changes in function of GI cells (usually resulting in diarrhea)
endotoxins
*source = outer cell membrane of most gram NEGATIVE bacteria (lipid A component of LPS)
*no specific action: host response to endotoxin can result in severe inflammation
*induces TNF, IL-1, and IL-6
*heat STABLE
*PYROGENIC and can cause shock
antitoxins
antibodies against exotoxins
toxoids
inactivated exotoxins (from heat, etc)
-don’t cause disease
-DO stimulate antitoxin production
*we can inject toxoids as vaccines to stimulate antitoxin production and provide immunity
superantigens
exotoxins that cause non-specific activation of T cells, resulting in polyclonal T cell activation and massive cytokine release
*excessive uncoordinated cytokine release causes rash, fever, and can lead to multi-organ failure
