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- colonization of a niche in the host (this includes attachment to cells)
- immunoevasion, evasion of the host's immune response
- immunosuppression, inhibition of the host's immune response
- entry into and exit out of cells (if the pathogen is an intracellular one)
- obtain nutrition from the host
Pathogens possess a wide array of virulence factors. Some are chromosomally encoded and intrinsic to the bacteria (e.g. capsules and endotoxin), whereas others are obtained from mobile genetic elements like plasmids and bacteriophages (e.g. some exotoxins). Virulence factors encoded on mobile genetic elements spread through horizontal gene transfer, and can convert harmless bacteria into dangerous pathogens. Bacteria like Escherichia coli O157:H7 gain the majority of their virulence from mobile genetic elements. Gram negative microbes secrete a variety of virulence factors at host-pathogen interface, via membrane vesicle trafficking as bacterial outer membrane vesicles for invasion, nutrition and other cell-cell communications.
Attachment, immunoevasion, and immunosuppression
Capsules, made of carbohydrate, form part of the outer structure of many bacterial cells including Neisseria meningitidis. Capsules play important roles in immune evasion, as they inhibit phagocytosis, as well as protecting the bacteria while outside the host.
Another group of virulence factors possessed by bacteria are immunoglobulin (Ig) proteases. Immunoglobulins are antibodies expressed and secreted by hosts in response to an infection. These immunoglobulins play a major role in destruction of the pathogen through mechanisms such as opsonization. Some bacteria, such as Streptococcus pyogenes, are able to break down the host's immunoglobulins using proteases.
Some bacteria, such as Streptococcus pyogenes, Staphylococcus aureus and Pseudomonas aeruginosa, produce a variety of enzymes which cause damage to host tissues. Enzymes include hyaluronidase, which breaks down the connective tissue component hyaluronic acid; a range of proteases and lipases; DNases, which break down DNA, and hemolysins which break down a variety of host cells, including red blood cells.
Endotoxin is a component (lipopolysaccharide (LPS)) of the cell wall of Gram-negative bacteria. It is the lipid A part of this LPS which is toxic. Lipid A is a very potent antigen and, as a result, stimulates an intense host immune response. As part of this immune response cytokines are released; these can cause the fever and other symptoms seen during disease. If a high amount of LPS is present then septic shock (or endotoxic shock) may result which, in severe cases, can lead to death.
Exotoxins are actively secreted by some bacteria and have a wide range of effects including inhibition of certain biochemical pathways in the host. The two most potent exotoxins known to man are the tetanus toxin (tetanospasmin) secreted by Clostridium tetani and the botulinum toxin secreted by Clostridium botulinum. Exotoxins are also produced by a range of other bacteria including Escherichia coli; Vibrio cholerae (causative agent of cholera); Clostridium perfringens (common causative agent of food poisoning as well as gas gangrene) and Clostridium difficile (causative agent of pseudomembranous colitis). A potent three-protein virulence factor produced by Bacillus anthracis, called anthrax toxin, plays a key role in anthrax pathogenesis.
Exotoxins are also produced by some fungi as a competitive resource. The toxins, named mycotoxins, deter other organisms from consuming the food colonised by the fungi. As with bacterial toxins, there is a wide array of fungal toxins. Arguably one of the more dangerous mycotoxins is aflatoxin produced by certain species of the genus Aspergillus (notably A. flavus). If ingested repeatedly, this toxin can cause serious liver damage.
Examples of virulence factors for Staphylococcus aureus are hyaluronidase, protease, coagulase, lipases, deoxyribonucleases and enterotoxins. Examples for Streptococcus pyogenes are M protein, lipoteichoic acid, hyaluronic acid capsule, destructive enzymes (including streptokinase, streptodornase, and hyaluronidase), and exotoxins (including streptolysin). Other virulence factors include factors required for biofilm formation (eg. sortases) and integrins (eg. beta-1 ad3).
Targetting virulence factors as a means of infection control
Strategies to target virulence factors and the genes encoding them have been proposed. Small molecules being investigated for their ability to inhibit virulence factors and virulence factor expression include alkaloids, flavonoids, and peptides.
- Trimeric Autotransporter Adhesins (TAA)
- Host-pathogen interface
- Membrane vesicle trafficking
- Bacterial outer membrane vesicles
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