Chapter 14 : Genetic Approaches to Understanding Pathogenicity

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This chapter presents selected examples of how genetic approaches have been used to identify virulence factors. The genetic approaches are based on five distinct concepts and assumptions about what might characterize virulence genes. The identification of -specific genes is based on the potential relationship between a pathogen-specific gene and the pathogenic phenotype. The biochemical and molecular functions of the gene products have remained elusive, but current speculations suggest that they may be involved in bacterial modulation of host immune cells. In summary, the comparison of strains with nonpathogenic strains or species has been a very useful approach to the identification of virulence genes. In many cases, the subsequent identification and mutagenesis of bacterial genes involved in putative virulence phenotypes have led to the identification of virulence genes. An alternative and more general approach has been to study in vitro systems in which species are able to survive interaction with primary or cultured macrophages. Examination of certain noninvasive mutants in animal infection models provides strong support for the importance of bacterial entry into intestinal cells. Bacterial binding and utilization of the enterochelin-iron complex is facilitated by Chr-TonB, an outer membrane receptor. Bacterial motility and chemotaxis require 50 different genes which encode chemical sensors, physical motors, directional switches, and components of the flagellar structure, as well as specific factors which export and assemble the flagellar structure. In fact, it has been speculated that motility and chemotaxis may be important for virulence.

Citation: Lee C. 1994. Genetic Approaches to Understanding Pathogenicity, p 215-234. In Miller V, Kaper J, Portnoy D, Isberg R (ed), Molecular Genetics of Bacterial Pathogenesis. ASM Press, Washington, DC. doi: 10.1128/9781555818340.ch14
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