15.4 Virulence factors of eukaryotic pathogens

Learning objectives

• Describe virulence factors unique to fungi and parasites
• Compare virulence factors of fungi and bacteria
• Explain the difference between protozoan parasites and helminths
• Describe how helminths evade the host immune system

Although fungi and parasites are important pathogens causing infectious diseases, their pathogenic mechanisms and virulence factors are not as well characterized as those of bacteria. Despite the relative lack of detailed mechanisms, the stages of pathogenesis and general mechanisms of virulence involved in disease production by these pathogens are similar to those of bacteria.

Fungal virulence

Pathogenic fungi can produce virulence factors that are similar to the bacterial virulence factors that have been discussed earlier in this chapter. In this section, we will look at the virulence factors associated with species of Candida , Cryptococcus, Claviceps, and Aspergillus .

Candida albicans is an opportunistic fungal pathogen and causative agent of oral thrush, vaginal yeast infections, and cutaneous candidiasis. Candida produces adhesins (surface glycoproteins) that bind to the phospholipids of epithelial and endothelial cells. To assist in spread and tissue invasion, Candida produces proteases and phospholipases (i.e., exoenzymes). One of these proteases degrades keratin, a structural protein found on epithelial cells, enhancing the ability of the fungus to invade host tissue. In animal studies, it has been shown that the addition of a protease inhibitor led to attenuation of Candida infection. K. Fallon et al. “Role of Aspartic Proteases in Disseminated Candida albicans Infection in Mice.” Infection and Immunity 65 no. 2 (1997):551–556. Similarly, the phospholipases can affect the integrity of host cell membranes to facilitate invasion.

The main virulence factor for Cryptococcus , a fungus that causes pneumonia and meningitis, is capsule production. The polysaccharide glucuronoxylomannan is the principal constituent of the Cryptococcus capsule. Similar to encapsulated bacterial cells, encapsulated Cryptococcus cells are more resistant to phagocytosis than nonencapsulated Cryptococcus , which are effectively phagocytosed and, therefore, less virulent.

Like some bacteria, many fungi produce exotoxins. Fungal toxins are called mycotoxin s . Claviceps purpurea , a fungus that grows on rye and related grains, produces a mycotoxin called ergot toxin, an alkaloid responsible for the disease known as ergotism . There are two forms of ergotism: gangrenous and convulsive. In gangrenous ergotism , the ergot toxin causes vasoconstriction, resulting in improper blood flow to the extremities, eventually leading to gangrene. A famous outbreak of gangrenous ergotism occurred in Eastern Europe during the 5th century AD due to the consumption of rye contaminated with C. purpurea . In convulsive ergotism , the toxin targets the central nervous system, causing mania and hallucinations.

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. C.P. Wild et al. “In-utero exposure to aflatoxin in west Africa.” Lancet 337 no. 8757 (1991):1602. 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.