VIRULENCE FACTORS are molecules produced by bacteria , viruses , fungi , and protozoa that add to their effectiveness and enable them to achieve the following:
* 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
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).
* The factors are used to assist and promote colonization of the host. These factors include adhesins , invasins , and antiphagocytic factors. * The factors, including toxins , hemolysins , and proteases , bring damage to the host.
* 1 Attachment, immunoevasion, and immunosuppression
* 2 Destructive enzymes
* 4 Toxins
* 5 Examples * 6 Targeting virulence factors as a means of infection control * 7 See also * 8 References
ATTACHMENT, IMMUNOEVASION, AND IMMUNOSUPPRESSION
Capsules, made of carbohydrate, form part of the outer structure of
many bacterial cells including
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
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.
Some bacteria, such as
VIRULENCE FACTORS DEALING IN THE ROLE OF 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 GEF or 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
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.
A major group of virulence factors are bacterial toxins. These are divided into two groups: endotoxins and exotoxins .
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
Lipid A is an endotoxin.
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 known exotoxins are the tetanus
toxin (tetanospasmin ) secreted by
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
TARGETING 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 . 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 alter from pathogenic to non-pathogenic, random mutations may be introduce 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 involving Yersinia 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 from Yersinia to a non-pathogenic E. 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.
* ^ Knipe, Howley, David, Peter (2013). Fields Virology, 6th Edition. Philadelphia, PA, USA: LIPPINCOTT WILLIAMS & WILKINS. p. 254. ISBN 978-1-4511-0563-6 . * ^ A B Levinson, W. (2010). Review of Medical Microbiology and Immunology (11th ed.). McGraw-Hill. * ^ https://www.hindawi.com/journals/jpath/2011/601905/ * ^ Keen, E. C. (December 2012). "Paradigms of pathogenesis: Targeting the mobile genetic elements of disease" . Frontiers in Cellular and Infection Microbiology. 2: 161. doi :10.3389/fcimb.2012.00161 . PMC 3522046 . PMID 23248780 . * ^ Deborah T. Hung; Elizabeth A. Shakhnovich; Emily Pierson; John J. Mekalanos (2005). "Small-molecule inhibitor of Vibrio cholerae virulence and intestinal colonization". Science. 310 (5748): 670–674. doi :10.1126/science.1116739 . PMID 16223984 . * ^ T.P. Tim Cushnie; Andrew J. Lamb (2011). "Recent advances in understanding the antibacterial properties of flavonoids". International Journal of Antimicrobial Agents. 38 (2): 99–107. doi :10.1016/j.ijantimicag.2011.02.014 . PMID 21514796 . * ^ Oscar Cirioni; Roberto Ghiselli; Daniele Minardi; Fiorenza Orlando; Federico Mocchegiani; Carmela Silvestri; Giovanni Muzzonigro; Vittorio Saba; Giorgio Scalise; Naomi Balaban & Andrea Giacometti (2007). "RNAIII-inhibiting peptide affects biofilm formation in a rat model of staphylococcal ureteral stent infection" . Antimicrobial Agents and Chemotherapy. 51 (12): 4518–4520. doi :10.1128/AAC.00808-07 . PMC 2167994 . PMID 17875996 .
* v * t * e
* enterotoxin * neurotoxin * hemotoxin * cardiotoxin * phototoxin
* Alpha toxin * Enterotoxin
* A * B
* type I
* type II
* type III
* AB toxin /AB5
* Lipid A
* Bacillus thuringiensis delta endotoxin
Androctonus australis hector insect toxin
REPTILE /SNAKE VENOM :
* note: some toxins are produced by lower species and pass through intermediate species
* CATEGORY * COMMONS * WIKIPROJECT