Question

Briefly discuss the mechanisms of virulence acquisition.

Answer 1

Virulence factors help bacteria to (1) invade the host, (2) cause disease, and (3) evade host defenses. The following are types of virulence factors:

Adherence Factors: Many pathogenic bacteria colonize mucosal sites by using pili (fimbriae) to adhere to cells.

Invasion Factors: Surface components that allow the bacterium to invade host cells can be encoded on plasmids, but more often are on the chromosome.

Capsules: Many bacteria are surrounded by capsules that protect them from opsonization and phagocytosis.

Endotoxins: The lipopolysaccharide endotoxins on Gram-negative bacteria cause fever, changes in blood pressure, inflammation, lethal shock, and many other toxic events.

Exotoxins: Exotoxins include several types of protein toxins and enzymes produced and/or secreted from pathogenic bacteria. Major categories include cytotoxins, neurotoxins, and enterotoxins.

Siderophores: Siderophores are iron-binding factors that allow some bacteria to compete with the host for iron, which is bound to hemoglobin, transferrin, and lactoferrin.

The virulence factors of bacteria can be divided into a number of functional types. These are discussed in the following sections:

Adherence and Colonization Factors

To establish an infection at such a site, a bacterium must adhere to the epithelium and multiply before the mucus and extruded epithelial cells are swept away. To accomplish this, bacteria have evolved attachment mechanisms, such as pili (fimbriae), that recognize and attach the bacteria to cells .Colonization factors (as they are often called) are produced by numerous bacterial pathogens and constitute an important part of the pathogenic mechanism of these bacteria. Some examples of piliated, adherent bacterial pathogens are V. cholerae, E. coli, Salmonella spp., N. gonorrheae, N. meningitidis, and Streptococcus pyogenes.

Invasion Factors

Mechanisms that enable a bacterium to invade eukaryotic cells facilitate entry at mucosal surfaces. Some of these invasive bacteria (such as Rickettsia and Chlamydia species) are obligate intracellular pathogens, but most are facultative intracellular pathogens . The specific bacterial surface factors that mediate invasion are not known in most instances, and often, multiple gene products are involved. Some Shigella invasion factors are encoded on a 140 megadalton plasmid, which, when conjugated into E. coli, gives these noninvasive bacteria the capacity to invade cells. Other invasion genes have also recently been identified in Salmonella and Yersinia pseudotuberculosis. The mechanisms of invasion of Rickettsia, and Chlamydia species are not well known.

Capsules and Other Surface Components

Bacteria have evolved numerous structural and metabolic virulence factors that enhance their Some bacteria and parasites have the ability to survive and multiply inside phagocytic cells. A classic example is Mycobacterium tuberculosis, whose survival seems to depend on the structure and composition of its cell surface. The parasite Toxoplasma gondii has the remarkable ability to block the fusion of lysosomes with the phagocytic vacuole. The hydrolytic enzymes contained in the lysosomes are unable, therefore, to contribute to the destruction of the parasite. The mechanism(s) by which bacteria such as Legionella pneumophila, Brucella abortus, and Listeriamonocytogenes remain unharmed inside phagocytes are not understood.

Endotoxins

Endotoxin is comprised of toxic lipopolysaccharide components of the outer membrane of Gram-negative bacteria . Endotoxin exerts profound biologic effects on the host and may be lethal. Because it is omnipresent in the environment, endotoxin must be removed from all medical supplies destined for injection or use during surgical procedures.

Exotoxins

Exotoxins, unlike the lipopolysaccharide endotoxin, are protein toxins released from viable bacteria. They form a class of poisons that is among the most potent, per unit weight, of all toxic substances. Most of the higher molecular-sized exotoxin proteins are heat labile; however, numerous low molecular-sized exotoxins are heat-stable peptides. Unlike endotoxin, which is a structural component of all Gram-negative cells, exotoxins are produced by some members of both Gram-positive and Gram-negative genera. The functions of these exotoxins for the bacteria are usually unknown, and the genes for most can be deleted with no noticeable effect on bacterial growth. In contrast to the extensive systemic and immune-system effects of endotoxin on the host, the site of action of most exotoxins is more localized and is confined to particular cell types or cell receptors. Tetanus toxin, for example, affects only internuncial neurons. In general, exotoxins are excellent antigens that elicit specific antibodies called antitoxins. Not all antibodies to exotoxins are protective, but some react with important binding sites or enzymatic sites on the exotoxin, resulting in complete inhibition of the toxic activity (i.e., neutralization).

Siderophores are substances produced by many bacteria (and some plants) to capture iron from the host. The absence of iron triggers transcription of the genes coding for the enzymes that synthesize siderophores, as well as for a set of surface protein receptors that recognize siderophores carrying bound iron. The binding constants of the siderophores for iron are so high that even iron bound to transferrin and lactoferrin is confiscated and taken up by the bacterial cells. An example of a bacterial siderophore is enterochelin, which is produced by Escherichia and Salmonella species. Classic experiments have demonstrated that Salmonella mutants that have lost the capacity to synthesize enterochelin lose virulence in an assay of lethality in mice. Injection of purified enterochelin along with the Salmonella mutants restores virulence to the bacteria. Therefore, siderophore production by many pathogenic bacteria is considered an important virulence mechanism.