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
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
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
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
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
Virulence factors dealing in the role of GTPases
6 Targeting virulence factors as a means of infection control
7 See also
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
Some bacteria, such as Streptococcus pyogenes,
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.
Virulence Factors basically Include the Antigenic Structure and The
Toxins produced by the organisms.
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
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
Bacteria to be colonized within a host cell.
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.
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.
Endotoxins are non-immunogenic, and
therefore do not have an acquired immune response.
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
Clostridium tetani and the botulinum toxin
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 extremely immunogenic meaning that they trigger the
humoral response (antibodies target the toxin).
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). Examples for Listeria
monocytogenes include internalin A, internalin B, lysteriolysin O, and
actA, all of which are used to help colonize the host. Examples for
Yersinia pestis are an altered form of lipopolysaccharide, type three
secretion system, and YopE and YopJ pathogenicity. The cytolytic
Candidalysin is produced during hyphal formation by Candida
albicans; it is an example of a virulence factor from a fungus. Other
virulence factors include factors required for biofilm formation (e.g.
sortases) and integrins (e.g. beta-1 and 3). 
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.
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.
Resistance-Nodulation-Cell Division Superfamily (RND)
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Staphylococcus aureus alpha/beta/delta
Toxic shock syndrome toxin
Enterotoxin B (SEB)
Verotoxin/shiga-like toxin (E. coli)
E. coli heat-stable enterotoxin/enterotoxin
Extracellular adenylate cyclase
Bacillus thuringiensis delta endotoxin
Clumping factor A
Fibronectin binding protein A
Amatoxin (alpha-amanitin, beta-amanitin, gamma-amanitin,
Androctonus australis hector insect toxin
note: some toxins are produced by lower species and pass through