Virulence factors Flashcards
Toxigenicity
P produce a wide range of biological poisons used to damage tissues, facillitate invasion and damage host’s defence mechanisms
Exotoxins
Produced by living P
Endotoxins
Lipopolysaccharides, componets of the cell wall of gram negative that are released from dead B or those undergoing division
Exo vs endo
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Exotoxin catrgories
- A-B toxins: specific cellular targets
- Cytolytic toxins- membrane disrupting
-Superantigens: cause immune overactivation
A-B exotoxins
-B component, like a viral receptor, is responsible for cellular specificty of toxin and mediates initial attachment to cell surface receptors
-Once A-B toxins binds to host cell, it is brought into cell by endocytosis and entrapped in a vacuole
-A and B subunits separate as vacuole acidifies after fusion with lysosome. The A subunit enters the cell cytoplasm and interferes with specific internal cell function that it targets
diptheria toxin
-An ACleavagB toxin produced by cells of Corynebacterium diphtheria which binds to the host cytoplasmic membrane by way of its B subunit
-Cleavage of toxin allows A subunit to calayse ADP-ribosylation of elongation factor (EF2) which prevents it from binding to ribisome
-Prevents prtotein synthesis and results in cell death
-B has to be infected by phage to be harmful
Neurological exotoxins
Clostridum tetani
Clostridium botulinum
Botulinum toxin mechanism
-Most potent AB toxin
-Botulinum toxin acts at the motor end plate and prevents release of acetylcholine from vesicles
-Results in lack of stimulus to muscle fibers, irreversible relaxation of muscles and flaccid paralysis
Acetylcholine mechanism
-Acetylcholine is normally released from vesicles at neuronal side of motor end plate
-it then binds to specific muscle receptors inducing contraction
Glycine mechanism
-released from inhibitory interneurons and acts on motor neurons to block excitation and rlease of acetylcholine at motor end plate
Tetanus mechanism
Tetanus binds to interneuron to prevent release of glycine from vesicles, resulting in a lack of inhibitory signals to motor neurons
-Results in constant release of acetylcholine to muscle fibers
-Irreversible contraction of muscles and spastic paralysis
Cytolytic exotoxins
They degrade the cytoplasmic membrane integrity which causes cells lysis and death
-or it forms pores in cytoplasmic membrane causing an increase in membrane permeability
Hemolysins
Lyse red blood cells
E. hemolysins
Staohlococcal alpha toxin kills nucleated cells and lyses erythrocytes
E.Cytolysins
Cytolysins from Acinetobacter sp. target immune cells like macrophages
Staphylococcal alpha toxin mechanism
-pore forming cytotoxin produced by Staphylococcus aureus
-Released as seven identical subunits which oligomerize in cytoplasmic membrane of target to form a pore which releases cell content
-In red blood cells, hemolysis occurs which indiactes cell lysis
Superantigen toxin
-Cause an overstimulation and therefore dysregulation of immune system
-often result of localised infection but with systemic effects
Superantigen producers
Gram-positive B, such as Staphylococcus aureus and Streptococcus pyogenes
-Superantigen poisoning can be triggered by food poisoning ( S.aureus), by toxic shock syndrome or by pyrogenic fever
Superantigen mechanism
-They crosslink MHC-II Antigen Presenting Receptor and T cell receptor resulting in T-cell activation
-It bypasses specific affinity and causes the activation of any Th cells and this results in overactivation of immune system
Superantigen lethal concentration
Concentration of less than 0.1pg/ml will stimulate T lymphocytes in an uncontrolled manner resulting in fever, shcock and death
Mitogen
Factor that promotes cell proliferation
do some gram negative not have endotoxins
No. The Lipid A component of the LPS is relatively consevred across different genera of gram negative B and is responsible for toxic properties of molecule
-therefore, toxic properties of Lipid A are similar regardless of gram-negative P
Lipid A mechanism
Triggers immune system’s inflammatory response which is usually beneficial
-Too much LPS in blood can cause an excessive inflammatory response, leading to severe drop in blood pressure, multi-organ failure and death
Detection of endotoxin
Presence can be detected by Limulus amoebocyte lysate (LAL) assay
-Overharvesting of horseshoe crabs is a concern as their blood is used in this assay
-These crabs have primitve blood that lyse in presence of LPS
Iron significance and need for iron transporters
-It is essential in biological processes such as e transfer, TCA cycle, nitrogen metabolism
-Iron is not freely availible in host organism but is complexed to storage proteins or bound to proteins/metal complexes such as heme, transferrin, ferritin
Siderophores
Virulence factors produced by both gram types
-They are high-affinity iron chelating molecules produced in response to iron deficiency
-P virulence is proportional to siderophore production
-Role is to sequester iron and transfer to B
Siderophore uses
Biofilm formation
toxicity towards mitochondria
-Used to deliver antibiotics to resistant B via membrane transporters
Trojan horse strategy
siderophores combined with antibiotic which allows it to be transferred into B
Virulence factor genetics
They are encoded on integrative genetic elements (MIGEs) within B chromosome and mobile elements such as plasmides and bacteriophages
Phage role in Virulence genetics (Prophage)
Many VF are encoded by prophages:
-Bacteriophages infect B and integrate into its genome to become prophages
-Prophage carries within its genome the VF genes
Prophage diseases
-Cholera and diptheria are caused by prophages that express the toxin
-Necotising fasciitis caused by prophage in Streptococcus
PAI
Pathogenicity islands
-Several virulence genes are clustered together on a chromosome
-seen in salmonella
PAI acquisition
Horizontal gene transfer via transduction, conjugation (sex pili) and transformation (phage) allow B to adapt very quickly to host mmune system
AbaR-type resistance islands
AbaR-type resistance islands (antibiotic resistance) are found in drug resistant Acinetobacter baumanii hospital strains
-Have transposon-like motility
