16.4: Pathogenicity and Virulence

Learning Objectives

• Explain the concept of pathogenicity (virulence) in terms of infectious and lethal dose
• Define and differentiate between pathogenicity and virulence
• Distinguish between primary and opportunistic pathogens and identify specific examples of each

Pathogenicity and Virulence

The ability of a microbial agent to cause disease is called pathogenicity, and the degree to which an organism is pathogenic is called virulence. Virulence is a continuum. On one end of the spectrum are organisms that are avirulent (not harmful) and on the other are organisms that are highly virulent. Highly virulent pathogens will almost always lead to a disease state when introduced to the body, and some may even cause multi-organ and body system failure in healthy individuals. Less virulent pathogens may cause an initial infection, but may not always cause severe illness. Pathogens with low virulence would more likely result in mild signs and symptoms of disease, such as low-grade fever, headache, or muscle aches. Some individuals might even be asymptomatic.

Definition: Term

Pathogenicity refers to the ability of a microorganism to cause disease. It is a qualitative trait—either a microbe is pathogenic (capable of causing disease) or non-pathogenic (not capable of causing disease).

Virulence refers to the degree or extent of pathogenicity, meaning how severe the disease caused by the pathogen is. It is a quantitative measure and can vary between different strains of the same species.

An example of a highly virulent microorganism is Bacillus anthracis, the pathogen responsible for anthrax. B. anthracis can produce different forms of disease, depending on the route of transmission (e.g., cutaneous injection, inhalation, ingestion). The most serious form of anthrax is inhalation anthrax. After B. anthracis spores are inhaled, they germinate. An active infection develops and the bacteria release potent toxins that cause edema (fluid buildup in tissues), hypoxia (a condition preventing oxygen from reaching tissues), and necrosis (cell death and inflammation). Signs and symptoms of inhalation anthrax include high fever, difficulty breathing, vomiting and coughing up blood, and severe chest pains suggestive of a heart attack. With inhalation anthrax, the toxins and bacteria enter the bloodstream, which can lead to multi-organ failure and death of the patient. If a gene (or genes) involved in pathogenesis is inactivated, the bacteria become less virulent or nonpathogenic.

Virulence of a pathogen can be quantified using controlled experiments with laboratory animals. Two important indicators of virulence are the median infectious dose (ID₅₀) and the median lethal dose (LD₅₀), both of which are typically determined experimentally using animal models. The ID₅₀ is the number of pathogen cells or virions required to cause active infection in 50% of inoculated animals. The LD₅₀ is the number of pathogenic cells, virions, or amount of toxin required to kill 50% of infected animals. To calculate these values, each group of animals is inoculated with one of a range of known numbers of pathogen cells or virions. In graphs like the one shown in Figure \(\PageIndex{2}\), the percentage of animals that have been infected (for ID₅₀) or killed (for LD₅₀) is plotted against the concentration of pathogen inoculated. Figure \(\PageIndex{2}\) represents data graphed from a hypothetical experiment measuring the LD₅₀ of a pathogen. Interpretation of the data from this graph indicates that the LD₅₀ of the pathogen for the test animals is 10⁴ pathogen cells or virions (depending upon the pathogen studied).

Figure \(\PageIndex{2}\): A graph like this is used to determine LD₅₀ by plotting pathogen concentration against the percent of infected test animals that have died. In this example, the LD₅₀ = 10⁴ pathogenic particles.

Table \(\PageIndex{2}\) lists selected foodborne pathogens and their ID₅₀ values in humans (as determined from epidemiologic data and studies on human volunteers). Keep in mind that these are median values. The actual infective dose for an individual can vary widely, depending on factors such as route of entry; the age, health, and immune status of the host; and environmental and pathogen-specific factors such as susceptibility to the acidic pH of the stomach. It is also important to note that a pathogen’s infective dose does not necessarily correlate with disease severity. For example, just a single cell of Salmonella enterica serotype Typhimurium can result in an active infection. The resultant disease, Salmonella gastroenteritis or salmonellosis, can cause nausea, vomiting, and diarrhea, but has a mortality rate of less than 1% in healthy adults. In contrast, S. enterica serotype Typhi has a much higher ID₅₀, typically requiring as many as 1,000 cells to produce infection. However, this serotype causes typhoid fever, a much more systemic and severe disease that has a mortality rate as high as 10% in untreated individuals.

Table \(\PageIndex{2}\): ID₅₀ for Selected Foodborne Diseases¹

Pathogen	ID50
Viruses
Hepatitis A virus	10–100
Norovirus	1–10
Rotavirus	10–100
Bacteria
Escherichia coli, enterohemorrhagic (EHEC, serotype O157)	10–100
E. coli, enteroinvasive (EIEC)	200–5,000
E. coli, enteropathogenic (EPEC)	10,000,000–10,000,000,000
E. coli, enterotoxigenic (ETEC)	10,000,000–10,000,000,000
Salmonella enterica serovar Typhi	<1,000
S. enterica serovar Typhimurium	≥1
Shigella dysenteriae	10–200
Vibrio cholerae (serotypes O139, O1)	1,000,000
V. parahemolyticus	100,000,000
Protozoa
Giardia lamblia	1
Cryptosporidium parvum	10–100

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Primary Pathogens versus Opportunistic Pathogens

Pathogens can be classified as either primary pathogens or opportunistic pathogens. A primary pathogen can cause disease in a host regardless of the host’s resident microbiota or immune system. An opportunistic pathogen, by contrast, can only cause disease in situations that compromise the host’s defenses, such as the body’s protective barriers, immune system, or normal microbiota. Individuals susceptible to opportunistic infections include the very young, the elderly, women who are pregnant, patients undergoing chemotherapy, people with immunodeficiencies (such as acquired immunodeficiency syndrome [AIDS]), patients who are recovering from surgery, and those who have had a breach of protective barriers (such as a severe wound or burn).

An example of a primary pathogen is enterohemorrhagic E. coli (EHEC), which produces a virulence factor known as Shiga toxin. This toxin inhibits protein synthesis, leading to severe and bloody diarrhea, inflammation, and renal failure, even in patients with healthy immune systems. Staphylococcus epidermidis, on the other hand, is an opportunistic pathogen that is among the most frequent causes of nosocomial disease.² S. epidermidis is a member of the normal microbiota of the skin, where it is generally avirulent. However, in hospitals, it can also grow in biofilms that form on catheters, implants, or other devices that are inserted into the body during surgical procedures. Once inside the body, S. epidermidis can cause serious infections such as endocarditis, and it produces virulence factors that promote the persistence of such infections.

Other members of the normal microbiota can also cause opportunistic infections under certain conditions. This often occurs when microbes that reside harmlessly in one body location end up in a different body system, where they cause disease. For example, E. coli normally found in the large intestine can cause a urinary tract infection if it enters the bladder. This is the leading cause of urinary tract infections among women.

Members of the normal microbiota may also cause disease when a shift in the environment of the body leads to overgrowth of a particular microorganism. For example, the yeast Candida is part of the normal microbiota of the skin, mouth, intestine, and vagina, but its population is kept in check by other organisms of the microbiota. If an individual is taking antibacterial medications, however, bacteria that would normally inhibit the growth of Candida can be killed off, leading to a sudden growth in the population of Candida, which is not affected by antibacterial medications because it is a fungus. An overgrowth of Candida can manifest as oral thrush (growth on mouth, throat, and tongue), a vaginal yeast infection, or cutaneous candidiasis. Other scenarios can also provide opportunities for Candida infections. Untreated diabetes can result in a high concentration of glucose in the saliva, which provides an optimal environment for the growth of Candida, resulting in thrush. Immunodeficiencies such as those seen in patients with HIV, AIDS, and cancer also lead to higher incidence of thrush. Vaginal yeast infections can result from decreases in estrogen levels during the menstruation or menopause. The amount of glycogen available to lactobacilli in the vagina is controlled by levels of estrogen; when estrogen levels are low, lactobacilli produce less lactic acid. The resultant increase in vaginal pH allows overgrowth of Candida in the vagina.

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Key Concepts and Summary

• Virulence, the degree to which a pathogen can cause disease, can be quantified by calculating either the ID₅₀ or LD₅₀ of a pathogen on a given population.
• Primary pathogens are capable of causing pathological changes associated with disease in a healthy individual, whereas opportunistic pathogens can only cause disease when the individual is compromised by a break in protective barriers or immunosuppression.
• Infections and disease can be caused by pathogens in the environment or microbes in an individual’s resident microbiota.

Footnotes

1. 1 Food and Drug Administration. “Bad Bug Book, Foodborne Pathogenic Microorganisms and Natural Toxins.” 2nd ed. Silver Spring, MD: US Food and Drug Administration; 2012.
2. 2 M. Otto. “Staphylococcus epidermidis--The ‘Accidental’ Pathogen.” Nature Reviews Microbiology 7 no. 8 (2009):555–567.
3. 3 The O in TORCH stands for “other.”
4. 4 D. Davies. “Understanding Biofilm Resistance to Antibacterial Agents.” Nature Reviews Drug Discovery 2 (2003):114–122.