SHARED THEMES OF ANTIGENIC VARIATION AND VIRULENCE IN BACTERIAL, PROTOZOAL, AND FUNGAL-INFECTIONS

Pathogenic microbes have evolved highly sophisticated mechanisms for c olonizing host tissues and evading ol deflecting assault by the immune response. The ability of these microbes to avoid clearance prolongs i nfection, thereby promoting their long-term survival within individual hosts and through transmission, between hosts. Many pathogens are cap able of extensive antigenic changes in the face of the multiple consti tutive and dynamic components of host immune defenses. As a result, hi ghly diverse populations that have widely different virulence properti es can arise from a single infecting organism (clone). in this review, we consider the molecular and genetic features of antigenic variation and corresponding host-parasite interactions of different pathogenic bacterial, fungal, and protozoan microorganisms. The host and microbia l molecules involved in these interactions often determine the adhesiv e, invasive, and antigenic properties of the infecting organisms and c an dramatically affect the virulence and pathobiology of individual in fections. Pathogens capable of such antigenic variation exhibit mechan isms of rapid mutability in confined chromosomal regions containing sp ecialized genes designated contingency genes. The mechanisms of hyperm utability of contingency genes are common to a variety of bacterial an d eukaryotic pathogens and include promoter alterations reading-frame shifts, gene conversion events, genomic rearrangements, and point muta tions.