Virulence
Encyclopedia
Virulence is by MeSH
definition the degree of pathogenicity
within a group or species of parasites
as indicated by case fatality rates and/or the ability of the organism to invade the tissues of the host
. The pathogenicity of an organism - its ability to cause disease
- is determined by its virulence factor
s. The noun
virulence derives from the adjective
virulent. Virulent can describe either disease severity or a pathogen's infectivity. The word virulent derives from the Latin word virulentus, meaning "a poisoned wound" or "full of poison."
In an ecological
context, virulence can be defined as the host's parasite-induced loss of fitness
. Virulence can be understood in terms of proximate causes—those specific traits of the pathogen that help make the host ill—and ultimate causes—the evolutionary pressures that lead to virulent traits occurring in a pathogen strain.
to cause disease is described in terms of the number of infecting bacteria, the route of entry into the body, the effects of host defense mechanisms, and intrinsic characteristics of the bacteria called virulence factors. Host-mediated pathogenesis is often important because the host can respond aggressively to infection with the result that host defense mechanisms do damage to host tissues while the infection is being countered.
The virulence factors of bacteria are typically proteins or other molecules that are synthesized by enzymes. These proteins are coded for by genes in chromosomal DNA, bacteriophage DNA or plasmid
s. Bacteria use quorum sensing
to synchronise release of the molecules. These are all proximate causes of morbidity in the host.
virulence factors determine whether infection occurs and how severe the resulting viral disease symptoms are. Viruses often require receptor proteins on host cells to which they specifically bind. Typically, these host cell proteins are endocytosed
and the bound virus then enters the host cell. Virulent viruses such as HIV
, which causes AIDS, have mechanisms for evading host defenses. HIV infects T-Helper Cells, which leads to a reduction of the adaptive immune response of the host and eventually leads to an immunocompromised state. Death results from opportunistic infections secondary to disruption of the immune system caused by the AIDS virus. Some viral virulence factors confer ability to replicate during the defensive inflammation responses of the host such as during virus-induced fever
. Many viruses can exist inside a host for long periods during which little damage is done. Extremely virulent strains can eventually evolve
by mutation and natural selection
within the virus population inside a host. The term "neurovirulent
" is used for viruses such as rabies
and herpes simplex
which can invade the nervous system
and cause disease there.
Extensively studied model organism
s of virulent viruses include virus T4 and other T-even bacteriophages which infect Escherichia coli
and a number of related Bacteria
.
The lytic life cycle
of virulent bacteriophages is contrasted by the temperate lifecycle
of Temperate bacteriophages.
, optimal virulence
increases with horizontal transmission
(between non-relatives) and decreases with vertical transmission
(from parent to child). This is because the fitness of the host is bound to the fitness in vertical transmission but is not so bound in horizontal transmission.
The pathogen population can evolve once it is in the host. There are three main hypotheses about why a pathogen evolves as it does. These three models help to explain the life history strategies
of parasites, including reproduction, migration within the host, virulence, etc. The three hypotheses are the Trade-Off Hypothesis, the Short-Sighted Evolution Hypothesis, and the Coincidental Evolution Hypothesis. All of these offer ultimate explanations for virulence in pathogens.
But this is not necessarily the case. Pathogen strains that kill the host can increase in frequency as long as the pathogen can transmit itself to a new host, whether before or after the host dies. The evolution of virulence in pathogens is a balance between the costs and benefits of virulence to the pathogen. For example, Mackinnon and Read (2004) and Paul et al. (2004) studied the malaria parasite using a rodent and chicken model respectively and found that there was trade-off between transmission success and virulence as defined by host mortality.
is caused by the soil bacterium Clostridium tetani
. After C. tetani bacteria enter a human wound, the bacteria may grow and divide rapidly, even though the human body is not their normal habitat. While dividing, C. tetani produce a neurotoxin that is lethal to humans. But it is selection in the bacterium's normal life cycle in the soil that leads it to produce this toxin, not any evolution with a human host. The bacterium finds itself inside a human instead of in the soil by mere happenstance. We can say that the neurotoxin is not directed at the human host.
More generally, the virulence of many pathogens in humans may not be a target of selection itself, but rather an accidental by-product of selection that operates on other traits.
Mesh
Mesh consists of semi-permeable barrier made of connected strands of metal, fiber, or other flexible/ductile material. Mesh is similar to web or net in that it has many attached or woven strands.-Types of mesh:...
definition the degree of pathogenicity
Pathogenicity
Pathogenicity is the ability of a pathogen to produce an infectious disease in an organism.It is often used interchangeably with the term "virulence", although virulence is used more specifically to describe the relative degree of damage done by a pathogen, or the degree of pathogenicity caused by...
within a group or species of parasites
Parasitism
Parasitism is a type of symbiotic relationship between organisms of different species where one organism, the parasite, benefits at the expense of the other, the host. Traditionally parasite referred to organisms with lifestages that needed more than one host . These are now called macroparasites...
as indicated by case fatality rates and/or the ability of the organism to invade the tissues of the host
Host (biology)
In biology, a host is an organism that harbors a parasite, or a mutual or commensal symbiont, typically providing nourishment and shelter. In botany, a host plant is one that supplies food resources and substrate for certain insects or other fauna...
. The pathogenicity of an organism - its ability to cause disease
Disease
A disease is an abnormal condition affecting the body of an organism. It is often construed to be a medical condition associated with specific symptoms and signs. It may be caused by external factors, such as infectious disease, or it may be caused by internal dysfunctions, such as autoimmune...
- is determined by its virulence factor
Virulence factor
Virulence factors are molecules expressed and secreted by pathogens that enable them to achieve the following:* colonization of a niche in the host...
s. The noun
Noun
In linguistics, a noun is a member of a large, open lexical category whose members can occur as the main word in the subject of a clause, the object of a verb, or the object of a preposition .Lexical categories are defined in terms of how their members combine with other kinds of...
virulence derives from the adjective
Adjective
In grammar, an adjective is a 'describing' word; the main syntactic role of which is to qualify a noun or noun phrase, giving more information about the object signified....
virulent. Virulent can describe either disease severity or a pathogen's infectivity. The word virulent derives from the Latin word virulentus, meaning "a poisoned wound" or "full of poison."
In an ecological
Ecology
Ecology is the scientific study of the relations that living organisms have with respect to each other and their natural environment. Variables of interest to ecologists include the composition, distribution, amount , number, and changing states of organisms within and among ecosystems...
context, virulence can be defined as the host's parasite-induced loss of fitness
Fitness (biology)
Fitness is a central idea in evolutionary theory. It can be defined either with respect to a genotype or to a phenotype in a given environment...
. Virulence can be understood in terms of proximate causes—those specific traits of the pathogen that help make the host ill—and ultimate causes—the evolutionary pressures that lead to virulent traits occurring in a pathogen strain.
Virulent bacteria
The ability of bacteriaBacteria
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...
to cause disease is described in terms of the number of infecting bacteria, the route of entry into the body, the effects of host defense mechanisms, and intrinsic characteristics of the bacteria called virulence factors. Host-mediated pathogenesis is often important because the host can respond aggressively to infection with the result that host defense mechanisms do damage to host tissues while the infection is being countered.
The virulence factors of bacteria are typically proteins or other molecules that are synthesized by enzymes. These proteins are coded for by genes in chromosomal DNA, bacteriophage DNA or 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. Bacteria use quorum sensing
Quorum sensing
Quorum sensing is a system of stimulus and response correlated to population density. Many species of bacteria use quorum sensing to coordinate gene expression according to the density of their local population. In similar fashion, some social insects use quorum sensing to determine where to nest...
to synchronise release of the molecules. These are all proximate causes of morbidity in the host.
Methods by which bacteria cause disease
- Adhesion. Many bacteria must first bind to host cell surfaces. Many bacterial and host molecules that are involved in the adhesion of bacteria to host cells have been identified. Often, the host cell receptors for bacteria are essential proteins for other functions.
- Colonization. Some virulent bacteria produce special proteins that allow them to colonize parts of the host body. Helicobacter pyloriHelicobacter pyloriHelicobacter pylori , previously named Campylobacter pyloridis, is a Gram-negative, microaerophilic bacterium found in the stomach. It was identified in 1982 by Barry Marshall and Robin Warren, who found that it was present in patients with chronic gastritis and gastric ulcers, conditions that were...
is able to survive in the acidic environment of the human stomach by producing the enzymeEnzymeEnzymes are proteins that catalyze chemical reactions. In enzymatic reactions, the molecules at the beginning of the process, called substrates, are converted into different molecules, called products. Almost all chemical reactions in a biological cell need enzymes in order to occur at rates...
ureaseUreaseUrease is an enzyme that catalyzes the hydrolysis of urea into carbon dioxide and ammonia. The reaction occurs as follows:In 1926, James Sumner showed that urease is a protein. Urease is found in bacteria, yeast, and several higher plants. The structure of urease was first solved by P.A...
. Colonization of the stomach lining by this bacterium can lead to Gastric ulcer and cancerCancerCancer , known medically as a malignant neoplasm, is a large group of different diseases, all involving unregulated cell growth. In cancer, cells divide and grow uncontrollably, forming malignant tumors, and invade nearby parts of the body. The cancer may also spread to more distant parts of the...
. The virulence of various strains of Helicobacter pylori tends to correlate with the level of production of urease. - Invasion. Some virulent bacteria produce proteins that either disrupt host cell membranes or stimulate endocytosis into host cells. These virulence factors allow the bacteria to enter host cells and facilitate entry into the body across epithelial tissue layers at the body surface.
- Immune response inhibitors. Many bacteria produce virulence factors that inhibit the host's immune system defenses. For example, a common bacterial strategy is to produce proteins that bind host antibodies. The polysaccharide capsule of Streptococcus pneumoniaeStreptococcus pneumoniaeStreptococcus pneumoniae, or pneumococcus, is Gram-positive, alpha-hemolytic, aerotolerant anaerobic member of the genus Streptococcus. A significant human pathogenic bacterium, S...
inhibits phagocytosis of the bacterium by host immune cells. - Toxins. Many virulence factors are proteins made by bacteria that poison host cells and cause tissue damage. For example, there are many food poisoning toxinToxinA toxin is a poisonous substance produced within living cells or organisms; man-made substances created by artificial processes are thus excluded...
s produced by bacteria that can contaminate human foods. Some of these can remain in "spoiled" food even after cooking and cause illness when the contaminated food is consumed. Some bacterial toxins are chemically altered and inactivated by the heat of cooking.
Virulent viruses
VirusViral
The adjective or adverb viral and the noun virality may refer to any viral phenomenon, that is, an object or pattern that is able to induce some agents to replicate it, resulting in many copies being produced and spread around....
virulence factors determine whether infection occurs and how severe the resulting viral disease symptoms are. Viruses often require receptor proteins on host cells to which they specifically bind. Typically, these host cell proteins are endocytosed
Endocytosis
Endocytosis is a process by which cells absorb molecules by engulfing them. It is used by all cells of the body because most substances important to them are large polar molecules that cannot pass through the hydrophobic plasma or cell membrane...
and the bound virus then enters the host cell. Virulent viruses such as HIV
HIV
Human immunodeficiency virus is a lentivirus that causes acquired immunodeficiency syndrome , a condition in humans in which progressive failure of the immune system allows life-threatening opportunistic infections and cancers to thrive...
, which causes AIDS, have mechanisms for evading host defenses. HIV infects T-Helper Cells, which leads to a reduction of the adaptive immune response of the host and eventually leads to an immunocompromised state. Death results from opportunistic infections secondary to disruption of the immune system caused by the AIDS virus. Some viral virulence factors confer ability to replicate during the defensive inflammation responses of the host such as during virus-induced fever
Fever
Fever is a common medical sign characterized by an elevation of temperature above the normal range of due to an increase in the body temperature regulatory set-point. This increase in set-point triggers increased muscle tone and shivering.As a person's temperature increases, there is, in...
. Many viruses can exist inside a host for long periods during which little damage is done. Extremely virulent strains can eventually evolve
Evolution
Evolution is any change across successive generations in the heritable characteristics of biological populations. Evolutionary processes give rise to diversity at every level of biological organisation, including species, individual organisms and molecules such as DNA and proteins.Life on Earth...
by mutation and natural selection
Natural selection
Natural selection is the nonrandom process by which biologic traits become either more or less common in a population as a function of differential reproduction of their bearers. It is a key mechanism of evolution....
within the virus population inside a host. The term "neurovirulent
Neurotropic virus
A neurotropic virus is a virus which is capable of infecting nerve cells, or which does so preferentially. Such viruses thereby largely evade the usual immune response—which acts only within the blood system.- Terminology :...
" is used for viruses such as rabies
Rabies
Rabies is a viral disease that causes acute encephalitis in warm-blooded animals. It is zoonotic , most commonly by a bite from an infected animal. For a human, rabies is almost invariably fatal if post-exposure prophylaxis is not administered prior to the onset of severe symptoms...
and herpes simplex
Herpes simplex
Herpes simplex is a viral disease caused by both Herpes simplex virus type 1 and type 2 . Infection with the herpes virus is categorized into one of several distinct disorders based on the site of infection. Oral herpes, the visible symptoms of which are colloquially called cold sores or fever...
which can invade the nervous system
Nervous system
The nervous system is an organ system containing a network of specialized cells called neurons that coordinate the actions of an animal and transmit signals between different parts of its body. In most animals the nervous system consists of two parts, central and peripheral. The central nervous...
and cause disease there.
Extensively studied model organism
Model organism
A model organism is a non-human species that is extensively studied to understand particular biological phenomena, with the expectation that discoveries made in the organism model will provide insight into the workings of other organisms. Model organisms are in vivo models and are widely used to...
s of virulent viruses include virus T4 and other T-even bacteriophages which infect 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...
and a number of related Bacteria
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...
.
The lytic life cycle
Lytic cycle
The lytic cycle is one of the two cycles of viral reproduction, the other being the lysogenic cycle. The lytic cycle is typically considered the main method of viral replication, since it results in the destruction of the infected cell...
of virulent bacteriophages is contrasted by the temperate lifecycle
Lysogeny
Lysogeny, or the lysogenic cycle, is one of two methods of viral reproduction . Lysogeny is characterized by integration of the bacteriophage nucleic acid into the host bacterium's genome...
of Temperate bacteriophages.
Evolution
According to evolutionary medicineEvolutionary medicine
Evolutionary medicine or Darwinian medicine is the application of modern evolutionary theory to understanding health and disease. It provides a complementary scientific approach to the present mechanistic explanations that dominate medical science, and particularly modern medical education...
, optimal virulence
Optimal virulence
Optimal virulence is a concept relating to the ecology of hosts and parasites. One definition of virulence is the host's parasite-induced loss of fitness. The parasite's fitness is determined by its success in transmitting offsprings to other hosts. At one time, the consensus was that over time,...
increases with horizontal transmission
Horizontal transmission
Horizontal transmission is the transmission of a bacterial, fungal, or viral infection between members of the same species that are not in a parent-child relationship....
(between non-relatives) and decreases with vertical transmission
Vertical transmission
Vertical transmission, also known as mother-to-child transmission, is the transmission of an infection or other disease from mother to child immediately before and after birth during the perinatal period. A pathogen's transmissibility refers to its capacity for vertical transmission...
(from parent to child). This is because the fitness of the host is bound to the fitness in vertical transmission but is not so bound in horizontal transmission.
The pathogen population can evolve once it is in the host. There are three main hypotheses about why a pathogen evolves as it does. These three models help to explain the life history strategies
Life history theory
Life history theory posits that the schedule and duration of key events in an organism's lifetime are shaped by natural selection to produce the largest possible number of surviving offspring...
of parasites, including reproduction, migration within the host, virulence, etc. The three hypotheses are the Trade-Off Hypothesis, the Short-Sighted Evolution Hypothesis, and the Coincidental Evolution Hypothesis. All of these offer ultimate explanations for virulence in pathogens.
Trade-off hypothesis
At one time, some biologists argued that pathogens would tend to evolve toward ever decreasing virulence because the death of the host (or even serious disability) is ultimately harmful to the pathogen living inside. For example, if the host dies, the pathogen population inside may die out entirely. Therefore, it was believed that less virulent pathogens that allowed the host to move around and interact with other hosts should have greater success reproducing and dispersing.But this is not necessarily the case. Pathogen strains that kill the host can increase in frequency as long as the pathogen can transmit itself to a new host, whether before or after the host dies. The evolution of virulence in pathogens is a balance between the costs and benefits of virulence to the pathogen. For example, Mackinnon and Read (2004) and Paul et al. (2004) studied the malaria parasite using a rodent and chicken model respectively and found that there was trade-off between transmission success and virulence as defined by host mortality.
Short-sighted evolution hypothesis
Short-sighted evolution suggests that the traits that increase reproduction rate and transmission to a new host will rise to high frequency within the pathogen population. These traits include the ability to reproduce sooner, reproduce faster, reproduce in higher numbers, live longer, survive against antibodies, or survive in parts of the body the pathogen does not normally infiltrate. These traits typically arise due to mutations, which occur more frequently in pathogen populations than in host populations, due to the pathogens' rapid generation time and immense numbers. After only a few generations, the mutations that enhance rapid reproduction or dispersal will increase in frequency. The same mutations that enhance the reproduction and dispersal of the pathogen also enhance its virulence in the host, causing much harm (disease and death). If the pathogen's virulence kills the host and interferes with its own transmission to a new host, virulence will be selected against. But as long as transmission continues despite the virulence, virulent pathogens will have the advantage. So, for example, virulence often increases within families, where transmission from one host to the next is likely, no matter how sick the host. Similarly, in crowded conditions such as refugee camps, virulence tends to increase over time since new hosts cannot escape the likelihood of infection.Coincidental evolution hypothesis
Some forms of pathogenic virulence did not co-evolve with the host. For example, tetanusTetanus
Tetanus is a medical condition characterized by a prolonged contraction of skeletal muscle fibers. The primary symptoms are caused by tetanospasmin, a neurotoxin produced by the Gram-positive, rod-shaped, obligate anaerobic bacterium Clostridium tetani...
is caused by the soil bacterium 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...
. After C. tetani bacteria enter a human wound, the bacteria may grow and divide rapidly, even though the human body is not their normal habitat. While dividing, C. tetani produce a neurotoxin that is lethal to humans. But it is selection in the bacterium's normal life cycle in the soil that leads it to produce this toxin, not any evolution with a human host. The bacterium finds itself inside a human instead of in the soil by mere happenstance. We can say that the neurotoxin is not directed at the human host.
More generally, the virulence of many pathogens in humans may not be a target of selection itself, but rather an accidental by-product of selection that operates on other traits.