Introduction: From Philosophy to Science

Abstract

Rickettsiae are bacterial obligate intracellular parasites ranging from harmless endosymbionts to the etiologic agents of some of the most devastating diseases known to mankind. Rickettsiae are primarily associated with arthropod vectors in which they may exist commensally and, in most cases, only accidentally infect humans. These fascinating microbes are the prototypical obligate intracellular parasites. Other than being extremely fastidious in their growth requirements, however, rickettsiae are typical gram-negative bacteria. Only a few intracellular parasites multiply within the cytoplasm of eukaryotic cells. In this environment, rickettsiae are provided with a rich source of biosynthetic precursors not normally encountered by free-living bacteria and have evolved a number of unique mechanisms to transport such metabolites as nucleotides and nucleotide sugars. The physiologic basis for their obligate parasitism, however, has remained elusive for > 90 years. Other than the obvious property of replicating inside eukaryotic cells, the molecular mechanisms of cellular damage are ill defined. The typhus-group rickettsiae multiply within host cells to great numbers without profound damage until lysis occurs. In contrast, the spotted fever-group rickettsiae spread rapidly from cell to cell by an actin-based motility. This property, in itself, is not sufficient to cause cell death, because avirulent spotted fever-group rickettsiae also spread by actin-based movement but do not cause lysis of the host cell. Despite the obvious limitations imposed by their obligate intracellular lifestyle and the current lack of methods for genetic manipulation, there are enough interesting biological properties of rickettsiae to offer an attractive area for research.