Virulence factors (preferably known as pathogenicity factors or effectors in botany) are cellular structures, molecules and regulatory systems that enable microbial pathogens (bacteria, viruses, fungi, and protozoa) to achieve the following:
colonization of a niche in the host (this includes movement towards and attachment to host cells) immunoevasion, evasion of the host's immune response immunosuppression, inhibition of the host's immune response (this includes leukocidin-mediated cell death) entry into and exit out of cells (if the pathogen is an intracellular one) obtain nutrition from the host Specific 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 bacteria 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. It has been found that many pathogens have converged on similar virulence factors to battle against eukaryotic host defenses. These obtained bacterial virulence factors have two different routes used to help them survive and grow:
The factors are used to assist and promote colonization of the host. These factors include adhesins, invasins, and antiphagocytic factors. Bacterial flagella that give motility are included in these virulence factors. The factors, including toxins, hemolysins and proteases, bring damage to the host.
Attachment, immunoevasion, and immunosuppression Bacteria produce various adhesins including lipoteichoic acid, trimeric autotransporter adhesins and a wide variety of other surface proteins to attach to host tissue. 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. Viruses also have notable virulence factors. Experimental research, for example, often focuses on creating environments that isolate and identify the role of "niche-specific virulence genes". These are genes that perform specific tasks within specific tissues/places at specific times; the sum total of niche-specific genes is the virus' virulence. Genes characteristic of this concept are those that control latency in some viruses like herpes. Murine gamma herpesvirus 68 (γHV68) and human herpesviruses depend on a subset of genes that allow them to maintain a chronic infection by reactivating when specific environmental conditions are met. Even though they are not essential for lytic phases of the virus, these latency genes are important for promoting chronic infection and continued replication within infected individuals.
Destructive enzymes 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.
GTPases A major group of virulence factors are proteins that can control the activation levels of GTPases. There are two ways in which they act. One is by acting as a guanine nucleotide exchange factor (GEF) or GTPase-activating protein (GAP), and proceeding to look like a normally eukaryotic cellular protein. The other is covalently modifying the GTPase itself. The first way is reversible; many bacteria like Salmonella have two proteins to turn the GTPases on and off. The other process is irreversible, using toxins to completely change the target GTPase and shut down or override gene expression. One example of a bacterial virulence factor acting like a eukaryotic protein is Salmonella protein SopE it acts as a GEF, turning the GTPase on to create more GTP. It does not modify anything, but overdrives normal cellular internalization process, making it easier for the Bacteria to be colonized within a host cell. YopT (Yersinia outer protein T) from Yersinia is an example of modification of the host. It modifies the proteolytic cleavage of carboxyl terminus of RhoA, releasing RhoA from the membrane. The mislocalization of RhoA causes downstream effectors to not work.
Toxins A major category of virulence factors are bacterial toxins. These are divided into two groups: endotoxins and exotoxins.
Endotoxins 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 an endotoxin. Endotoxins trigger intense inflammation. They bind to receptors on monocytes causing the release of inflammatory mediators which induce degranulation. 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. As glycolipids (as opposed to peptides), endotoxins are not bound by B or T-cell receptors and do not elicit an adaptive immune response.
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