Especially, in animals, it can be identified as the degree of damage caused by a microbe to its host. As described above, virulence occurs while spreading pathogens in their hosts. Especially, virulence is related to the pathogenicity as virulence factors are the major determinants of pathogenicity.
In bacteria, virulence factors include proteins and other molecules. Moreover, the virulence bacteria cause diseases in a mechanism, which composes of five steps. They are adhesion, colonization, invasion, immune response inhibitors, and toxins. Significantly, adhesion is the first step in causing diseases.
During adhesion, bacteria bind to the surface of the host cell. Then, they undergo multiplication in order to form colonies. After that, these virulence bacteria invade host cells by disrupting host cell membranes. In the meanwhile, most of the bacteria produce immune response inhibitors, which inhibit the defense mechanisms of the host immune system. Also, the proteins made by these bacteria serve as toxins, which cause tissue damages. For instance, both immune response inhibitors and toxins are virulence factors.
Pathogenicity refers to the absolute ability of an infectious agent to cause disease in a host, while virulence refers to the ability of the pathogen to infect or damage the host. Pathogenicity follows virulence, while virulence is in the initial stage of host-pathogen interactions.
Glycocalyx produced by bacteria in a biofilm allows the cells to adhere to host tissues and to medical devices such as the catheter surface shown here. Molecules either proteins or carbohydrates called adhesins are found on the surface of certain pathogens and bind to specific receptors glycoproteins on host cells.
Adhesins are present on the fimbriae and flagella of bacteria, the cilia of protozoa, and the capsids or membranes of viruses. Protozoans can also use hooks and barbs for adhesion; spike proteins on viruses also enhance viral adhesion. The production of glycocalyces slime layers and capsules Figure 4 , with their high sugar and protein content, can also allow certain bacterial pathogens to attach to cells.
Biofilm growth can also act as an adhesion factor. A biofilm is a community of bacteria that produce a glycocalyx, known as extrapolymeric substance EPS , that allows the biofilm to attach to a surface. Persistent Pseudomonas aeruginosa infections are common in patients suffering from cystic fibrosis, burn wounds, and middle-ear infections otitis media because P.
The EPS allows the bacteria to adhere to the host cells and makes it harder for the host to physically remove the pathogen. The EPS not only allows for attachment but provides protection against the immune system and antibiotic treatments, preventing antibiotics from reaching the bacterial cells within the biofilm. In addition, not all bacteria in a biofilm are rapidly growing; some are in stationary phase. Since antibiotics are most effective against rapidly growing bacteria, portions of bacteria in a biofilm are protected against antibiotics.
Once adhesion is successful, invasion can proceed. Invasion involves the dissemination of a pathogen throughout local tissues or the body. Pathogens may produce exoenzymes or toxins, which serve as virulence factors that allow them to colonize and damage host tissues as they spread deeper into the body. Pathogens may also produce virulence factors that protect them against immune system defenses. Figure 5 shows the invasion of H. Figure 5. Some are obligate intracellular pathogens meaning they can only reproduce inside of host cells and others are facultative intracellular pathogens meaning they can reproduce either inside or outside of host cells.
By entering the host cells, intracellular pathogens are able to evade some mechanisms of the immune system while also exploiting the nutrients in the host cell. Entry to a cell can occur by endocytosis. For most kinds of host cells, pathogens use one of two different mechanisms for endocytosis and entry. One mechanism relies on effector proteins secreted by the pathogen; these effector proteins trigger entry into the host cell.
This is the method that Salmonella and Shigella use when invading intestinal epithelial cells. When these pathogens come in contact with epithelial cells in the intestine, they secrete effector molecules that cause protrusions of membrane ruffles that bring the bacterial cell in.
This process is called membrane ruffling. The second mechanism relies on surface proteins expressed on the pathogen that bind to receptors on the host cell, resulting in entry. For example, Yersinia pseudotuberculosis produces a surface protein known as invasin that binds to beta-1 integrins expressed on the surface of host cells.
Some host cells, such as white blood cells and other phagocytes of the immune system, actively endocytose pathogens in a process called phagocytosis. Although phagocytosis allows the pathogen to gain entry to the host cell, in most cases, the host cell kills and degrades the pathogen by using digestive enzymes.
Normally, when a pathogen is ingested by a phagocyte, it is enclosed within a phagosome in the cytoplasm; the phagosome fuses with a lysosome to form a phagolysosome, where digestive enzymes kill the pathogen see Pathogen Recognition and Phagocytosis. However, some intracellular pathogens have the ability to survive and multiply within phagocytes. Bacteria such as Mycobacterium tuberculosis , Legionella pneumophila , and Salmonella species use a slightly different mechanism to evade being digested by the phagocyte.
These bacteria prevent the fusion of the phagosome with the lysosome, thus remaining alive and dividing within the phagosome. Following invasion, successful multiplication of the pathogen leads to infection. Infections can be described as local, focal, or systemic, depending on the extent of the infection. A local infection is confined to a small area of the body, typically near the portal of entry. For example, a hair follicle infected by Staphylococcus aureus infection may result in a boil around the site of infection, but the bacterium is largely contained to this small location.
Other examples of local infections that involve more extensive tissue involvement include urinary tract infections confined to the bladder or pneumonia confined to the lungs. In a focal infection , a localized pathogen, or the toxins it produces, can spread to a secondary location.
For example, a dental hygienist nicking the gum with a sharp tool can lead to a local infection in the gum by Streptococcus bacteria of the normal oral microbiota. These Streptococcus spp. When an infection becomes disseminated throughout the body, we call it a systemic infection. For example, infection by the varicella-zoster virus typically gains entry through a mucous membrane of the upper respiratory system.
It then spreads throughout the body, resulting in the classic red skin lesions associated with chickenpox. Since these lesions are not sites of initial infection, they are signs of a systemic infection. Sometimes a primary infection , the initial infection caused by one pathogen, can lead to a secondary infection by another pathogen. For example, the immune system of a patient with a primary infection by HIV becomes compromised, making the patient more susceptible to secondary diseases like oral thrush and others caused by opportunistic pathogens.
Similarly, a primary infection by Influenzavirus damages and decreases the defense mechanisms of the lungs, making patients more susceptible to a secondary pneumonia by a bacterial pathogen like Haemophilus influenzae or Streptococcus pneumoniae.
Some secondary infections can even develop as a result of treatment for a primary infection. Antibiotic therapy targeting the primary pathogen can cause collateral damage to the normal microbiota, creating an opening for opportunistic pathogens. Anita, a year-old mother of three, goes to an urgent care center complaining of pelvic pressure, frequent and painful urination, abdominal cramps, and occasional blood-tinged urine.
Suspecting a urinary tract infection UTI , the physician requests a urine sample and sends it to the lab for a urinalysis.
Since it will take approximately 24 hours to get the results of the culturing, the physician immediately starts Anita on the antibiotic ciprofloxacin.
The next day, the microbiology lab confirms the presence of E. After taking her antibiotics for 1 week, Anita returns to the clinic complaining that the prescription is not working. Although the painful urination has subsided, she is now experiencing vaginal itching, burning, and discharge. After a brief examination, the physician explains to Anita that the antibiotics were likely successful in killing the E.
The new symptoms that Anita has reported are consistent with a secondary yeast infection by Candida albicans , an opportunistic fungus that normally resides in the vagina but is inhibited by the bacteria that normally reside in the same environment.
To confirm this diagnosis, a microscope slide of a direct vaginal smear is prepared from the discharge to check for the presence of yeast.
A sample of the discharge accompanies this slide to the microbiology lab to determine if there has been an increase in the population of yeast causing vaginitis. After the microbiology lab confirms the diagnosis, the physician prescribes an antifungal drug for Anita to use to eliminate her secondary yeast infection.
For a pathogen to persist, it must put itself in a position to be transmitted to a new host, leaving the infected host through a portal of exit Figure 6.
As with portals of entry, many pathogens are adapted to use a particular portal of exit. Similar to portals of entry, the most common portals of exit include the skin and the respiratory, urogenital, and gastrointestinal tracts. Coughing and sneezing can expel pathogens from the respiratory tract.
A single sneeze can send thousands of virus particles into the air. Secretions and excretions can transport pathogens out of other portals of exit. Feces, urine, semen, vaginal secretions, tears, sweat, and shed skin cells can all serve as vehicles for a pathogen to leave the body.
Pathogens that rely on insect vectors for transmission exit the body in the blood extracted by a biting insect. Similarly, some pathogens exit the body in blood extracted by needles. Figure 6. The question implies that the ability to cause damage or disease is an inherent microbial property, but in fact these characteristics only exist in the context of a susceptible host.
Therefore, when a host is immune, pathogenicity is not expressed. What is important to recognize is that pathogenicity and virulence are microbial properties that can only be expressed in a susceptible host. The immune system does not distinguish between pathogens and commensals.
In fact, the question of whether pathogenicity is a microbial trait and the question of whether hosts distinguish so-called pathogens from non-pathogens have the same answer: pathogenicity is an outcome of host-microbe interaction and is thus inextricably linked to characteristics of the host as well as those of the microbe.
Commensals also called the microbiota are acquired by infection soon after birth, after which they establish residence in mucosal niches where they replicate, and there is increasing evidence that the microbiota play a crucial role in the development of the immune system and that the immune response to the bacteria in mucosal niches helps maintain barriers to invasion on surfaces exposed to potentially harmful microorganisms.
The commensal bacteria themselves do no harm, provided that the immune system and mucosal barriers remain normal and intact. The immune system provides a large variety of tools - cells and molecules - that recognize, react to and control microbial growth and invasion, often in a manner that does not result in host damage or disease, and when this happens, there is no readout. In a situation where there is host damage or disease, there are two possibilities: either the immune system did not contain or control the microbe and the microbe caused host damage, or the host immune response to the microbe caused damage or disease, whether the microbe was controlled, or contained, or not.
Thus, the immune system does not discriminate between microbes; it reacts to them, albeit differently depending on characteristics of the host and characteristics of the microbe, with the response defining an outcome that reflects the behavior of host and microbial factors. The obvious case is where the immune response to some microbe is insufficient, and the microbe can replicate and disseminate throughout the host.
In this instance, the lack of an immune response translates into the potential for pathogenicity as mentioned above, even commensal bacteria can be pathogenic if the immune system is impaired or the mucosal barrier is disrupted.
An interesting paradox occurs in the case of two bacteria that produce toxins generally regarded as factors increasing the virulence of the microbe: s taphylococci that produce a so-called leukocidin, and pneumococci that produce a toxin called pneumolysin.
Because these toxins also activate the innate immune response, bacteria that do not produce them can sometimes be more pathogenic than bacteria that do. Thus, when the immune response to a microbe is insufficient, microbial factors can cause damage, and when microbial factors fail to stimulate the immune system, the microbe can disseminate and cause disease.
At the other end of the spectrum, when the immune response to a microbe is too exuberant, it can be the immune response itself that is responsible for the pathology.
When damage occurs in this setting, it is most commonly due to detrimental inflammation and can occur whether the microbe is controlled or contained or not. Examples of this phenomenon include diseases like toxic shock syndrome, in which it is the potent activation of the immune response by a microbial component that does the damage.
In these diseases, antimicrobial therapy is often unsuccessful because it does not reduce the host inflammatory response. In fact, new directions in the treatment of infectious diseases that are marked by exuberant inflammation increasingly involve the use of anti-inflammatory therapies.
Although these terms are often used interchangeably, they have different meanings [6]. Pathogenicity is defined by the capacity of a microbe to cause damage in a susceptible host. Virulence is defined as the relative capacity of a microbe to cause damage in a host. Although both pathogenicity and virulence can only be manifest in a susceptible host, pathogenicity is a discontinuous variable, that is, there is or is not pathogenicity, whereas virulence is a continuous variable, that is, it is defined by the amount of damage or disease that is manifest.
Virulence is a relative term for there is no absolute measure of virulence and virulence is always measured relative to another microorganism for example, an attenuated strain, or a different species.
Although they differ as delineated here, pathogenicity and virulence are both microbial variables that can only be expressed in a susceptible host, underscoring that each is dependent on host variables. There is no difference between an opportunistic pathogen and any other kind of pathogen. The definition that is often used for opportunistic pathogens is that these microbes cause disease in people with impaired immunity but not in normal individuals.
However, this definition is purely operational: the same microbe - consider Candida albicans and Staphylococcus epidermidis - can cause disease in one individual but live harmlessly in others, which means that the same microbe would be called an opportunist in one individual and a commensal in another. Indeed, the identification of certain microbes as a cause of disease in certain hosts can unmask or be a sentinel for an underlying immunodeficiency.
However, although the absence of certain host factors or products can lead to an inability to control or contain certain microbes, the determinants of pathogenicity and virulence for these microbes depend on host and microbial factors, as is the case for all microbes. In our view there are only microbes and hosts and the outcomes of their interactions, which include commensalism, colonization, latency and disease.
Hence, attempts to classify microbes as pathogens, non-pathogens, opportunists, commensals and so forth are misguided because they attribute a property to the microbe that is instead a function of the host, the microbe, and their interaction. Yes and no. Pathogenicity and virulence are emergent properties, meaning that they cannot be predicted directly from the properties of the microorganism. Thus, microbial pathogenicity is intrinsically unpredictable.
Host and microbial characteristics are subject to predictable and unpredictable changes prompted by known, unknown, and random environmental, immunological, and other factors.
Thus, as it is an outcome of host-microbe interaction whereby each entity is subject to independent and dependent changes at any point in time, pathogenicity is an emergent property.
Not altogether.
0コメント