Chapter 19 : Covert Operations: the Adaptable Plan of Attack Deployed by Pathogenic Bacteria

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Bacterial pathogenesis may be viewed as a developmental program wherein the virulence traits observed are the summation of the relative contributions of nature versus nurture; i.e., a series of complex interactions between bacterial genes and the environments experienced during the infective process. Repression or inhibition of virulence functions may also improve bacterial fitness by mediating immune avoidance mechanisms, the establishment and maintenance of subclinical infections, or bacterial transmission to new hosts or the environment. Owing to the dehydration associated with massive diarrhea (several liters/day), cholera is one of the most rapidly fatal diseases known. Analysis of the coordinate control of bacterial virulence gene expression in response to environmental and genetic signals in the laboratory setting (in vitro) has contributed significantly to defining the functions that confer microbial pathogenicity. This chapter talks about , spp, and spp in detail. The study of microbial pathogens in the context of their natural host(s) provides insights into microbial pathogenicity that cannot be revealed from in vitro studies alone. Classification of virulence genes based on their preferential expression in host tissues provides a means to understand the ecology of infection as well as spatial and functional relationships between bacterial and host gene products. The currently available means to determine the level of expression of all messenger RNA (with DNA arrays) and all proteins (with two-dimensional analyses) will permit the determination of gene activation and protein expression during the varied stages of infection.

Citation: Mahan M, Sinsheimer R, Shimp W, Heithoff D. 2011. Covert Operations: the Adaptable Plan of Attack Deployed by Pathogenic Bacteria, p 185-200. In Maloy S, Hughes K, Casadesús J (ed), The Lure of Bacterial Genetics. ASM Press, Washington, DC. doi: 10.1128/9781555816810.ch19

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Gene Expression and Regulation
Bacterial Pathogenesis
PhoPQ Two-Component Regulatory System
Type III Secretion System
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Identification of microbial genes within the context of the host. (a) IVET is a promoter trap strategy in which bacterial promoters are selected that drive the expression of a gene required for growth within the host (e.g., auxotrophy or antibiotic resistance). Complementation in the animal demands elevated levels of bacterial gene expression compared to growth on laboratory medium detected by transcriptional fusions to the genes of interest; Lac (black circles); Lac (open circles). (b) DFI is a promoter trap strategy that uses FACS to screen for bacterial genes that show altered levels of expression in host tissues relative to laboratory medium. Transcription is detected by GFP generated by transcriptional GFP fusions to the genes of interest; high expression (black circles), equivalent expression (gray circles), and low expression (open circles). (c) STM is a negative selection scheme for bacterial mutants present in the initial inoculum that do not survive in the animal. Mutants represented in the initial inoculum but not recovered from host tissues specify genes that are required for infection (open circles); mutants recovered from infected tissues and laboratory medium are designated by black circles. (d) Comparative genomics (CG) approaches use bacterial cDNAs recovered from bacteria residing in infected tissues versus laboratory medium. Direct comparison of the expression of individual bacterial genes provides an assessment of their relative expression levels in vivo versus in vitro; high expression (black symbols), equivalent expression (gray symbols), and low expression (open symbols).

Citation: Mahan M, Sinsheimer R, Shimp W, Heithoff D. 2011. Covert Operations: the Adaptable Plan of Attack Deployed by Pathogenic Bacteria, p 185-200. In Maloy S, Hughes K, Casadesús J (ed), The Lure of Bacterial Genetics. ASM Press, Washington, DC. doi: 10.1128/9781555816810.ch19
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