Microbiology, 2021

644 15 • Microbial Mechanisms of Pathogenicity
The mycotoxin aflatoxin is a virulence factor produced by the fungus Aspergillus, an opportunistic pathogen
that can enter the body via contaminated food or by inhalation. Inhalation of the fungus can lead to the chronic
pulmonary disease aspergillosis, characterized by fever, bloody sputum, and/or asthma. Aflatoxin acts in the
host as both a mutagen (a substance that causes mutations in DNA) and a carcinogen (a substance involved in
causing cancer), and has been associated with the development of liver cancer. Aflatoxin has also been shown
to cross the blood-placental barrier. 10 A second mycotoxin produced by Aspergillus is gliotoxin. This toxin
promotes virulence by inducing host cells to self-destruct and by evading the host’s immune response by
inhibiting the function of phagocytic cells as well as the pro-inflammatory response. Like Candida, Aspergillus
also produces several proteases. One is elastase, which breaks down the protein elastin found in the
connective tissue of the lung, leading to the development of lung disease. Another is catalase, an enzyme that
protects the fungus from hydrogen peroxide produced by the immune system to destroy pathogens.
CHECK YOUR UNDERSTANDING
• List virulence factors common to bacteria and fungi.
• What functions do mycotoxins perform to help fungi survive in the host?
Protozoan Virulence
Protozoan pathogens are unicellular eukaryotic parasites that have virulence factors and pathogenic
mechanisms analogous to prokaryotic and viral pathogens, including adhesins, toxins, antigenic variation, and
the ability to survive inside phagocytic vesicles.
Protozoans often have unique features for attaching to host cells. The protozoan Giardia lamblia, which causes
the intestinal disease giardiasis, uses a large adhesive disc composed of microtubules to attach to the
intestinal mucosa. During adhesion, the flagella of G. lamblia move in a manner that draws fluid out from
under the disc, resulting in an area of lower pressure that facilitates adhesion to epithelial cells. Giardia does
not invade the intestinal cells but rather causes inflammation (possibly through the release of cytopathic
substances that cause damage to the cells) and shortens the intestinal villi, inhibiting absorption of nutrients.
Some protozoans are capable of antigenic variation. The obligate intracellular pathogen Plasmodium
falciparum (one of the causative agents of malaria) resides inside red blood cells, where it produces an adhesin
membrane protein known as PfEMP1. This protein is expressed on the surface of the infected erythrocytes,
causing blood cells to stick to each other and to the walls of blood vessels. This process impedes blood flow,
sometimes leading to organ failure, anemia, jaundice (yellowing of skin and sclera of the eyes due to buildup of
bilirubin from lysed red blood cells), and, subsequently, death. Although PfEMP1 can be recognized by the
host’s immune system, antigenic variations in the structure of the protein over time prevent it from being
easily recognized and eliminated. This allows malaria to persist as a chronic infection in many individuals.
The virulence factors of Trypanosoma brucei, the causative agent of African sleeping sickness, include the
abilities to form capsules and undergo antigenic variation. T. brucei evades phagocytosis by producing a dense
glycoprotein coat that resembles a bacterial capsule. Over time, host antibodies are produced that recognize
this coat, but T. brucei is able to alter the structure of the glycoprotein to evade recognition.
CHECK YOUR UNDERSTANDING
• Explain how antigenic variation by protozoan pathogens helps them survive in the host.
Helminth Virulence
Helminths, or parasitic worms, are multicellular eukaryotic parasites that depend heavily on virulence factors
that allow them to gain entry to host tissues. For example, the aquatic larval form of Schistosoma mansoni,
which causes schistosomiasis, penetrates intact skin with the aid of proteases that degrade skin proteins,
including elastin.
10 C.P. Wild et al. “In-utero exposure to aflatoxin in west Africa.” Lancet 337 no. 8757 (1991):1602.
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