Virulence Factor

Virulence Factor

Virulence factors are molecules expressed and secreted by pathogens (bacteria, viruses, fungi and protozoa) that enable them to achieve the following:

• colonization of a niche in the host (this includes adhesion to cells) for example, Trimeric Autotransporter Adhesins (TAA)
• 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.

Virulence factors are very often responsible for causing disease in the host because they are often responsible for converting non-pathogenic bacteria into dangerous pathogens. In bacteria, virulence factors are often encoded on mobile genetic elements, such as bacteriophages, and can easily be spread through horizontal gene transfer. Some bacteria, such as Escherichia coli O157:H7, gain the majority of their virulence from mobile genetic elements. Strategies to target these specific virulence factors and mobile genetic elements have been proposed.

Pathogens possess a wide array of virulence factors. Some are intrinsic to the bacteria (e.g. capsules and endotoxin) whereas others are obtained from plasmids (e.g. some toxins).

A major group of virulence factors are bacterial toxins. These are divided into two groups: endotoxins and exotoxins. Lipopolysaccharide (LPS) is a prototypical example of an endotoxin. Lipopolysaccharide is a component of the cell wall of Gram-negative bacteria. The Lipid A component of LPS has toxic properties. The LPS 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.

Toxins 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.

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 (causative agent of scarlet fever and many other conditions), 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.

Capsules, made of carbohydrate, form part of the outer structure of many bacterial cells including Neisseria meningitidis (causative agent of meningitis). Capsules play important roles in immune evasion, as they inhibit phagocytosis, as well as protecting the bacteria while outside a host.