VIRULENCE FACTORS: WHAT THEY ARE AND EXAMPLES - BIOLOGY - 2025

The virulence factors are those abilities of microorganisms to invade the tissues of a host through toxic molecules, bacteria and other pathogens in order to obtain food or fixed cells. Therefore, the host could become ill if their immune system is not able to stop the virulence factors of the pathogen.

In some species, one or more of these factors may be absent, and if they are not present the ability to cause the disease may be attenuated or completely absent.

Colored scanning electron micrograph of the bacterium that causes gonorrhea, Neisseria gonorrhea. Taken and edited from: NIAID.

What are virulence factors?

Virulence factors are usually protein toxins or other molecules produced by the pathogen to circumvent the host's immune defense system. However, they also include structural components such as capsules, flagella, and fimbriae or pilis, which allow it to reach or protect itself from the host cell.

Capsule

The capsule is a mucous envelope, formed mainly by polysaccharides, which can be produced by both Gram-positive and Gram-negative bacteria and which is located externally to the cell wall.

The capsule is not vital for the bacteria, since its loss does not affect its viability, but it can cause changes in the morphology of the colony and loss of its virulence. For example, there are several strains of Haemophilus influenzae that can be differentiated by the presence or absence of the capsule.

There are six serotypes of this bacterium (a. B, c, d, e, and f) that have capsules, each of which is antigenically different. Of these colonies, Haemophilus influenzae serotype b has a capsule composed of polyribosylribitol phosphate that protects it from phagocytosis and is the main strain responsible for diseases in humans.

Flagellum

The flagellum is a long, mobile, whip-shaped structure usually used for movement. It is present in bacteria and other unicellular organisms, as well as in some cells of multicellular organisms.

Sometimes the flagellum is considered a virulence factor. For example, in Pseudomonas it presents positive chemotaxis towards some molecules, such as sugars. Furthermore, virulence in these bacteria has been associated with the presence of a flagellum, as some mutants that lack it hardly cause infections.

Fimbriae

The fimbriae or pilis are structures that are mainly found in Gram negative bacteria. They are filamentous, protein in nature, shorter and thinner than flagella and differ from flagella because they are not used for displacement.

In some bacterial species these structures are considered virulence factors, since they play an important role in the adherence and colonization of mucosal surfaces. They are also involved in a flagella-independent surface translocation method called twitching moti.

An example of these structures as a virulence factor are the type IV pilis or N-methyl-phenylalanine pilis present in Pseudomonas aeruginosa.

Adhesins

Bacteria produce various types of factors that allow them to adhere effectively to the tissues of their host. These substances bind to specific receptors on the surface of tissues, thus preventing their elimination by the host.

Adhesins include lipoteichoic acids, trimeric self-transporting adhesins, and hemagglutinating pilis. For example, Corynebacteria diphteriae possesses adhesive properties that are independent of diphtheria toxin production and that are due to factors such as hemagglutinins, hydrophobins, exposed sugar residues, and enzymes with transialidase activity.

Helycobacter pylori virulence factor. Taken and edited from: user: Y_tambe.

Immunosuppressants

Some virulence factors work by eliminating immunological substances used by the hosts. For example, bacteria such as Streptococcus pyogenes possess immunoglobulin proteases. Immunoglobulins are antibodies that attack and destroy bacteria through mechanisms such as opsonization.

Mycobacterium ulcerans, the causative agent of Buruli ulcer in humans, produces an immunosuppressant called mycolactone. This toxin also causes tissue destruction.

Immunoevasion

The main components of the outer membrane of Gram negative bacteria are lipopolysaccharides and lipooligosaccharides. The structure of the lipooligosaccharides that make up the Haemophilus influenzae membrane mimic the glycosphingolipids of humans to evade detection by the immune system.

Destructive enzymes

Some bacteria produce various enzymes that damage host tissues. For example, Porphyromonas gingivalis produces polysaccharidases and a large number of proteases that degrade many of the components of the extracellular matrix of host tissues.

This bacterium is responsible for periodontal diseases and the destruction caused by its enzymes is the main responsible for the inflammation that is observed in this type of disease.

Other enzymes produced by bacteria include hyalurodinase, lipases, DNases, and hemolysins.

Endotoxins

The lipopolysaccharide that is part of the outer membrane of Gram negative bacteria is composed of three parts, lipid A, a central polysaccharide and polysaccharide O. Lipid A is immersed in the membrane and possesses toxic activity, due to this the Lipopolysaccharide is also called endotoxin.

When bacterial lysis occurs, endotoxin is released and stimulates the release of pyrogens, proteins that cause fever. It can also cause endotoxic shock that can lead to death.

Exotoxins

They are substances released by various groups of bacteria that have a wide range of effects and include neurotoxins, cytotoxins, calagenases, lipases, lecithinases, DNases, RNases, hemolysins, among others. The most potent exotoxins known to date are tetanus and botulism, secreted by Clostridium tetani and C. botulinum, respectively.

Other virulence factors

In addition to the aforementioned factors, there are others such as polyketides, siderophores, alginates, factors that control GTPases and others that modify the host's immune response (for example neuraminidase).

Examples

Neisseria gonorrhea

Neisseria gonorrhoeae is an intracellular diplococcus responsible for the sexually transmitted disease known as gonorrhea or gonorrhea. In this species, researchers have identified different virulence factors, among which they mention: pilis or fimbriae, proteins I (Por), II (Opa) and III (Rpm), constituents of the outer membrane.

Also virulence factors are lipooligosaccharides, peptidoglycan and other proteins such as Lip (H8) and Fbp, they also produce an IgA1 protease, responsible for inactivating an important immunoglobulin in human mucosa called IgA1.

Helicobacter pylori

Helicobacter pylori is the main cause of some gastrointestinal diseases, such as gastritis, peptic ulcers and also some types of neoplasms.

There are several virulence factors described for this species, among which are: a) the activity of urease, an enzyme that catalyzes the hydrolysis of urea to provide ammonium and carbamate, which can cause lesions in the gastric epithelium; b) other adherence factors, necessary for bacterial colonization.

Hemagglutinins induce changes in the immune response due to the fact that they have a biochemical composition similar to that of some antigens present in blood groups. In addition, it has a gene associated with vacuolization and another with cytotoxic activity that are only present in virulent strains.

Neisseria meningitidis

Bacterial meningitis is a contagious disease caused by Neisseria meningitidis, or meningococcus. Virulence factors for this bacterium include the polysaccharide capsule that protect it from the host's inflammatory response and the type IV pili that promote bacterial adherence.

Other virulence factors of this species are class 5 proteins (Opa) and Opc, IgA1 proteases as well as components of the cell wall.

References

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5. C. Alfaro (2005). Neisseria meningitidis pathogenesis. Medical Journal of the National Children's Hospital.
6. G. Pardi (2004). Some considerations about Neisseria gonorrhoeae. Venezuelan Dental Act.