 | This articleneeds additional citations forverification. Please helpimprove this article byadding citations to reliable sources. Unsourced material may be challenged and removed. Find sources: "Virulence factor" – news ·newspapers ·books ·scholar ·JSTOR(September 2014) (Learn how and when to remove this message) |
Virulence factors (preferably known as pathogenicity factors or effectors inbotany) are cellular structures, molecules and regulatory systems that enable microbial pathogens (bacteria,viruses,fungi, andprotozoa) to achieve the following:[1][2]
Specific pathogens possess a wide array of virulence factors. Some arechromosomally encoded and intrinsic to the bacteria (e.g. capsules andendotoxin), whereas others are obtained frommobile genetic elements likeplasmids andbacteriophages (e.g. some exotoxins). Virulence factors encoded on mobile genetic elements spread throughhorizontal gene transfer, and can convert harmless bacteria into dangerous pathogens. Bacteria likeEscherichia coli O157:H7 gain the majority of theirvirulence from mobile genetic elements.Gram-negative bacteria secrete a variety of virulence factors athost–pathogen interface, viamembrane vesicle trafficking asbacterial 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 againsteukaryotic host defenses. These obtained bacterial virulence factors have two different routes used to help them survive and grow:
Bacteria produce variousadhesins includinglipoteichoic 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 includingNeisseria meningitidis. Capsules play important roles in immune evasion, as they inhibitphagocytosis, as well as protecting the bacteria while outside the host.
Another group of virulence factors possessed by bacteria areimmunoglobulin (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 asopsonization. Some bacteria, such asStreptococcus 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 virulencegenes". 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 controllatency in some viruses like herpes.Murine gamma herpesvirus 68 (γHV68) and humanherpesviruses 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 forlytic phases of the virus, these latency genes are important for promoting chronic infection and continued replication within infected individuals.[6]
Some bacteria, such asStreptococcus pyogenes,Staphylococcus aureus andPseudomonas aeruginosa, produce a variety of enzymes which cause damage to host tissues. Enzymes includehyaluronidase, which breaks down the connective tissue componenthyaluronic acid; a range of proteases andlipases;DNases, which break down DNA; andhemolysins, which break down a variety of host cells, including red blood cells.
A major group of virulence factors are proteins that can control the activation levels ofGTPases. There are two ways in which they act. One is by acting as aguanine nucleotide exchange factor (GEF) orGTPase-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) fromYersinia 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.
A major category of virulence factors are bacterial toxins. These are divided into two groups:endotoxins andexotoxins.[4]
Endotoxin is a component (lipopolysaccharide (LPS)) of the cell wall of gram-negative bacteria. It is thelipid A part of this LPS which is toxic.[4] Lipid A is an endotoxin. Endotoxins trigger intense inflammation. They bind to receptors onmonocytes causing the release of inflammatory mediators which inducedegranulation. 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.
Some bacteria secrete exotoxins, which have a wide range of effects, including inhibiting certain biochemical pathways in the host. The two most potent known exotoxins[4] are the tetanus toxin (tetanospasmin) secreted byClostridium tetani and thebotulinum toxin secreted byClostridium botulinum. Exotoxins are also produced by a range of other bacteria includingEscherichia coli;Vibrio cholerae (causative agent ofcholera);Clostridium perfringens (common causative agent offood poisoning as well asgas gangrene) andClostridioides difficile (causative agent ofpseudomembranous colitis). A potent three-protein virulence factor produced byBacillus anthracis, calledanthrax toxin, plays a key role inanthrax pathogenesis. Exotoxins are extremely immunogenic and trigger the humoral response (antibodies target the toxin).
Exotoxins are also produced by somefungi as a competitive resource. The toxins, namedmycotoxins, deter other organisms from consuming the food the fungi colonise. As with bacterial toxins, there is a wide array of fungal toxins. Arguably one of the more dangerous mycotoxins isaflatoxin produced by certain species of the genusAspergillus (notablyA. flavus). If ingested repeatedly, this toxin can cause serious liver damage.
Examples of virulence factors forStaphylococcus aureus arehyaluronidase,protease,coagulase,lipases,deoxyribonucleases andenterotoxins. Examples forStreptococcus pyogenes areM protein,lipoteichoic acid,hyaluronic acid capsule, destructive enzymes (includingstreptokinase,streptodornase, andhyaluronidase), andexotoxins (includingstreptolysin). Examples forListeria monocytogenes include internalin A, internalin B,listeriolysin O, and actA, all of which are used to help colonize the host. Examples forYersinia pestis are an altered form of lipopolysaccharide, type three secretion system, and YopE and YopJ pathogenicity. The cytolytic peptideCandidalysin is produced duringhyphal formation byCandida albicans; it is an example of a virulence factor from a fungus. Other virulence factors include factors required forbiofilm formation (e.g.sortases) andintegrins (e.g. beta-1 and 3).[7]
In enteric pathogens such as Salmonella and E. coli, the membrane proteinIgaA regulates the Rcs phosphorelay system, which modulates virulence factors including capsule synthesis, biofilm formation, and motility.
Strategies to target virulence factors and the genes encoding them have been proposed.[8]Small molecules being investigated for their ability to inhibit virulence factors and virulence factorexpression includealkaloids,[9]flavonoids,[10] andpeptides.[11]Experimental studies are done to characterize specific bacterial pathogens and to identify their specific virulence factors. Scientists are trying to better understand these virulence factors through identification and analysis to better understand the infectious process in hopes that new diagnostic techniques, specific antimicrobial compounds, and effective vaccines or toxoids may be eventually produced to treat and prevent infection.There are three general experimental ways for the virulence factors to be identified: biochemically, immunologically, and genetically. For the most part, the genetic approach is the most extensive way in identifying the bacterial virulence factors. Bacterial DNA can be altered from pathogenic to non-pathogenic, random mutations may be introduced to their genome, specific genes encoding for membrane or secretory products may be identified and mutated, and genes that regulate virulence genes maybe identified.
Experiments involvingYersinia pseudotuberculosis have been used to change the virulence phenotype of non-pathogenic bacteria to pathogenic. Because of horizontal gene transfer, it is possible to transfer the a clone of the DNA fromYersinia to a non-pathogenicE. coli and have them express the pathogenic virulence factor.Transposon, a DNA element inserted at random, mutagenesis of bacteria DNA is also a highly used experimental technique done by scientists. These transposons carry a marker that can be identified within the DNA. When placed at random, the transposon may be placed next to a virulence factor or placed in the middle of a virulence factor gene, which stops the expression of the virulence factor. By doing so, scientists can make a library of the genes using these markers and easily find the genes that cause the virulence factor.
{{cite book}}: CS1 maint: multiple names: authors list (link)