Mechanisms for the virulence of Nocardia

Abstract

Nocardia is a Gram positive, strictly aerobic actinomycete found in soil, water and on vegetable matter. Pathogenic species cause a variety of acute and chronic diseases in humans and animals with the lungs and skin being primary sites for these infections. Virulent strains of Nocardia are facultative intracellular pathogens that are not killed by normal macrophages, monocytes or polymorphonuclear neutrophils. The mechanisms whereby these organisms avoid being killed are multiple and complex, and include: 1) the ability to inhibit phagosome-lysosome fusion; 2) neutralize phagosomal acidification; 3) modulate lysosomal enzymes; and, 4) resist toxic oxidative metabolites. The virulence of most nocardiae is growth stage dependent, and the relative degrees of pathogenicity correlate with specific changes in the structure of components of the cell wall during the growth cycle. The most important of these is the glycolipid, trehalose dimycolate. In addition, virulent strains of N. asteroides secrete a unique superoxide dismutase and contain increased amounts of catalase that protect these organisms from the oxidative killing mechanisms of phagocytes. Furthermore, Nocardia should be considered a primary pathogen of the brain since blood borne organisms have a specific predilection for this region of the body. Studies have shown that there is specific binding or adherence to subpopulations of capillary endothelial cells in regions of the brain. Following attachment, the endothelial cells phagocytize these nocardiae and they pass through the basement membrane to enter the brain parenchyma. The nocardiae invade neurons and grow within most types of brain cells without inducing an inflammatory response. The mechanisms for adherence, invasion and growth within the brain are not known.