Virulence factor
Encyclopedia
Virulence factors are molecules expressed and secreted by pathogens (bacteria
, virus
es, fungi and protozoa
) that enable them to achieve the following:
Virulence factors are very often responsible for causing disease in the host as they inhibit certain host functions.
Pathogens possess a wide array of virulence factors. Some are intrinsic to the bacteria (e.g. capsules and endotoxin
) whereas others are obtained from plasmid
s (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 affects 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
(causative agent of food poisoning as well as gas gangrene) and Clostridium difficile
(causative agent of pseudomembranous colitis).
Toxins are also produced by some fungi as a competitive resource. The toxins, named mycotoxin
s, 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 Aspergillus 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.
are hyaluronidase
, protease
, coagulase
, lipase
s, deoxyribonuclease
s and enterotoxins
Some examples of virulence factors for Streptococcus pyogenes
are M protein
, lipoteichoic acid
, hyaluronic acid capsule, invasins such as streptokinase
, streptodornase, hyaluronidase
, spenceronic, dorsettonic, and streptolysin
s, and excotoxins
some other virulence factors are adhesion factors, biofilms(for example sortase
s or things that attach to integrin
s notably beta-1 ad3 , extracellular enzymes, toxins and antiphagocytic factors.
Bacteria
Bacteria are a large domain of prokaryotic microorganisms. Typically a few micrometres in length, bacteria have a wide range of shapes, ranging from spheres to rods and spirals...
, virus
Virus
A virus is a small infectious agent that can replicate only inside the living cells of organisms. Viruses infect all types of organisms, from animals and plants to bacteria and archaea...
es, fungi and protozoa
Protozoa
Protozoa are a diverse group of single-cells eukaryotic organisms, many of which are motile. Throughout history, protozoa have been defined as single-cell protists with animal-like behavior, e.g., movement...
) that enable them to achieve the following:
- colonization of a niche in the host (this includes adhesion to cells)
- Immunoevasion, evasion of the host's immune response
- ImmunosuppressionImmunosuppressionImmunosuppression involves an act that reduces the activation or efficacy of the immune system. Some portions of the immune system itself have immuno-suppressive effects on other parts of the immune system, and immunosuppression may occur as an adverse reaction to treatment of other...
, 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 as they inhibit certain host functions.
Pathogens possess a wide array of virulence factors. Some are intrinsic to the bacteria (e.g. capsules and endotoxin
Endotoxin
Endotoxins are toxins associated with some Gram-negative bacteria. An "endotoxin" is a toxin that is a structural molecule of the bacteria that is recognized by the immune system.-Gram negative:...
) whereas others are obtained from plasmid
Plasmid
In microbiology and genetics, a plasmid is a DNA molecule that is separate from, and can replicate independently of, the chromosomal DNA. They are double-stranded and, in many cases, circular...
s (e.g. some toxins).
A major group of virulence factors are bacterial toxins. These are divided into two groups: endotoxins and exotoxins. Lipopolysaccharide
Lipopolysaccharide
Lipopolysaccharides , also known as lipoglycans, are large molecules consisting of a lipid and a polysaccharide joined by a covalent bond; they are found in the outer membrane of Gram-negative bacteria, act as endotoxins and elicit strong immune responses in animals.-Functions:LPS is the major...
(LPS) is a prototypical example of an endotoxin. Lipopolysaccharide
Lipopolysaccharide
Lipopolysaccharides , also known as lipoglycans, are large molecules consisting of a lipid and a polysaccharide joined by a covalent bond; they are found in the outer membrane of Gram-negative bacteria, act as endotoxins and elicit strong immune responses in animals.-Functions:LPS is the major...
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 affects including inhibition of certain biochemical pathways in the host. The two most potent exotoxins known to man are the tetanus toxin (tetanospasmin
Tetanospasmin
Tetanus toxin is an extremely potent neurotoxin produced by the vegetative cell of Clostridium tetani in anaerobic conditions, causing tetanus. It has no known function for clostridia in the soil environment where they are normally encountered. It is also called spasmogenic toxin, tetanospasmin or...
) secreted by Clostridium tetani
Clostridium tetani
Clostridium tetani is a rod-shaped, anaerobic bacterium of the genus Clostridium. Like other Clostridium species, it is Gram-positive, and its appearance on a gram stain resembles tennis rackets or drumsticks. C. tetani is found as spores in soil or in the gastrointestinal tract of animals. C...
and the botulinum toxin secreted by Clostridium botulinum
Clostridium botulinum
Clostridium botulinum is a Gram-positive, rod-shaped bacterium that produces several toxins. The best known are its neurotoxins, subdivided in types A-G, that cause the flaccid muscular paralysis seen in botulism. It is also the main paralytic agent in botox. C. botulinum is an anaerobic...
. Exotoxins are also produced by a range of other bacteria including Escherichia coli
Escherichia coli
Escherichia coli is a Gram-negative, rod-shaped bacterium that is commonly found in the lower intestine of warm-blooded organisms . Most E. coli strains are harmless, but some serotypes can cause serious food poisoning in humans, and are occasionally responsible for product recalls...
; Vibrio cholerae (causative agent of cholera); Clostridium perfringens
Clostridium perfringens
Clostridium perfringens is a Gram-positive, rod-shaped, anaerobic, spore-forming bacterium of the genus Clostridium. C. perfringens is ever present in nature and can be found as a normal component of decaying vegetation, marine sediment, the intestinal tract of humans and other vertebrates,...
(causative agent of food poisoning as well as gas gangrene) and Clostridium difficile
Clostridium difficile
Clostridium difficile , also known as "CDF/cdf", or "C...
(causative agent of pseudomembranous colitis).
Toxins are also produced by some fungi as a competitive resource. The toxins, named mycotoxin
Mycotoxin
A mycotoxin is a toxic secondary metabolite produced by organisms of the fungus kingdom, commonly known as molds. The term ‘mycotoxin’ is usually reserved for the toxic chemical products produced by fungi that readily colonize crops...
s, 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 Aspergillus 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
Streptococcus pyogenes
Streptococcus pyogenes is a spherical, Gram-positive bacterium that is the cause of group A streptococcal infections. S. pyogenes displays streptococcal group A antigen on its cell wall. S...
, Staphylococcus aureus
Staphylococcus aureus
Staphylococcus aureus is a facultative anaerobic Gram-positive coccal bacterium. It is frequently found as part of the normal skin flora on the skin and nasal passages. It is estimated that 20% of the human population are long-term carriers of S. aureus. S. aureus is the most common species of...
and Pseudomonas aeruginosa
Pseudomonas aeruginosa
Pseudomonas aeruginosa is a common bacterium that can cause disease in animals, including humans. It is found in soil, water, skin flora, and most man-made environments throughout the world. It thrives not only in normal atmospheres, but also in hypoxic atmospheres, and has, thus, colonized many...
, produce a variety of enzymes which cause damage to host tissues. Enzymes include hyaluronidase
Hyaluronidase
The hyaluronidases are a family of enzymes that degrade hyaluronic acid.In humans, there are six associated genes, including HYAL1, HYAL2, HYAL3, and PH-20/SPAM1.-Use as a drug:...
, 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
Neisseria meningitidis
Neisseria meningitidis, often referred to as meningococcus, is a bacterium that can cause meningitis and other forms of meningococcal disease such as meningococcemia, a life threatening sepsis. N. meningitidis is a major cause of morbidity and mortality during childhood in industrialized countries...
(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.
Examples
Examples of virulence factors for Staphylococcus aureusStaphylococcus aureus
Staphylococcus aureus is a facultative anaerobic Gram-positive coccal bacterium. It is frequently found as part of the normal skin flora on the skin and nasal passages. It is estimated that 20% of the human population are long-term carriers of S. aureus. S. aureus is the most common species of...
are hyaluronidase
Hyaluronidase
The hyaluronidases are a family of enzymes that degrade hyaluronic acid.In humans, there are six associated genes, including HYAL1, HYAL2, HYAL3, and PH-20/SPAM1.-Use as a drug:...
, protease
Protease
A protease is any enzyme that conducts proteolysis, that is, begins protein catabolism by hydrolysis of the peptide bonds that link amino acids together in the polypeptide chain forming the protein....
, coagulase
Coagulase
Coagulase is a protein produced by several microorganisms that enables the conversion of fibrinogen to fibrin. In the laboratory, it is used to distinguish between different types of Staphylococcus isolates. Coagulase negativity excludes S. aureus. That is to say, S...
, lipase
Lipase
A lipase is an enzyme that catalyzes the formation or cleavage of fats . Lipases are a subclass of the esterases.Lipases perform essential roles in the digestion, transport and processing of dietary lipids in most, if not all, living organisms...
s, deoxyribonuclease
Deoxyribonuclease
A deoxyribonuclease is any enzyme that catalyzes the hydrolytic cleavage of phosphodiester linkages in the DNA backbone. Thus, deoxyribonucleases are one type of nuclease...
s and enterotoxins
Some examples of virulence factors for Streptococcus pyogenes
Streptococcus pyogenes
Streptococcus pyogenes is a spherical, Gram-positive bacterium that is the cause of group A streptococcal infections. S. pyogenes displays streptococcal group A antigen on its cell wall. S...
are M protein
M protein
M protein may refer to:* M protein ', a virulence factor of the bacterium Streptococcus pyogenes* Another name for paraprotein, an abnormal protein in the urine or blood, often seen in multiple myeloma or MGUS...
, lipoteichoic acid
Lipoteichoic acid
Lipoteichoic acid is a major constituent of the cell wall of Gram-positive bacteria. These organisms have an inner membrane and, external to it, a thick peptidoglycan layer. It consists of teichoic acids, long chains of ribitol phosphate and is anchored to the lipid bilayer via a glyceride...
, hyaluronic acid capsule, invasins such as streptokinase
Streptokinase
Streptokinase , a protein secreted by several species of streptococci can bind and activate human plasminogen. SK is used as an effective and inexpensive thrombolysis medication in some cases of myocardial infarction and pulmonary embolism...
, streptodornase, hyaluronidase
Hyaluronidase
The hyaluronidases are a family of enzymes that degrade hyaluronic acid.In humans, there are six associated genes, including HYAL1, HYAL2, HYAL3, and PH-20/SPAM1.-Use as a drug:...
, spenceronic, dorsettonic, and streptolysin
Streptolysin
Streptolysin is a streptococcal hemolytic exotoxin.Types include Streptolysin O , which is oxygen-labile, and Streptolysin S , which is oxygen-stable.An antibody, anti-streptolysin O, can be detected in an antistreptolysin O titre....
s, and excotoxins
some other virulence factors are adhesion factors, biofilms(for example sortase
Sortase
Sortase refers to a group of prokaryotic enzymes which catalyze the assembly of pilins into pili, and the anchoring of pili to the cell wall. They act as both proteases and transpeptidases. Sortase, a transpeptidase present in almost all Gram-positive bacteria, anchors a range of important...
s or things that attach to integrin
Integrin
Integrins are receptors that mediate attachment between a cell and the tissues surrounding it, which may be other cells or the ECM. They also play a role in cell signaling and thereby regulate cellular shape, motility, and the cell cycle....
s notably beta-1 ad3 , extracellular enzymes, toxins and antiphagocytic factors.