Mechanisms of bacterial virulence.
In this review the nature of prokaryotic parasites was first discussed with emphasis on the evolution of virulence. Subsequently, nonspecific mechanisms of host defense were considered with emphasis on recent findings relating to bacterial killing by serum and professional phagocytes. Based on this background, the nature of virulence factors required for growth of pathogens in the nonimmune host was considered. Strategies used by extracellular and intracellular parasites were compared. It is evident from the resulting overview of experimental findings that knowledge concerning virulence of extracellular parasites outweighs that collected for both facultative and obligate intracellular parasites. Remaining problems regarding extracellular parasitism include precise resolution of the nature of serum resistance, pilus-independent adhesion, tissue invasiveness, and resistance to phagocytosis. Solutions to these questions will probably arise during the course of studies primarily emphasizing bacterial structure and function. Unresolved problems concerning intracellular parasites include definition of regulatory changes involved in adaptation for intra- and extracellular growth, the nature of reactions preventing phagosome-lysosome fusion, mechanisms of survival within phagolysosomes, and explanations for host-cell dependence. These topics provide real problems in cellular and molecular biology, and they will probably be resolved by those familiar with these disciplines. The ability of parasitic prokaryotes to shut off otherwise effective specific immune responses was shown to cross phenotypic lines. Resolution of these somewhat sinister mechanisms of virulence will require an understanding of fundamental immune processes. Further study of bacterial virulence factors will probably provide an understanding of basic cellular processes relevant to other biological disciplines. Indeed, information of this nature may not be obtainable by any other experimental approach.