Chapter 20 : Phenotypic Variation and Gene Regulation in the Pathogenesis of Infection

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Phenotypic Variation and Gene Regulation in the Pathogenesis of Infection, Page 1 of 2

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Salmonellosis is an infectious problem of global significance. Mammals, birds, and reptiles are susceptible to infections that manifest as localized (gastroenteritis) and systemic (enteric fever) diseases. Humans are not without defense against , and two important clinical observations support the essential nature of immune responses in resisting systemic infection. First, nontyphoidal bacteremia is commonly observed in children during their second year of life, consistent with host vulnerability resulting from a developing immune system with limited capabilities for B-cell immunoglobulin responses. Second, nontyphoidal bacteremia is associated with significant mortality among adults with defects in cellular immunity, especially HIV infection. The interaction of with phagocytes is critical to the pathogenesis of infection, because bacteria that cannot survive in macrophages are avirulent; the bacteria transit from mucosal to systemic sites in phagocytes and predominantly replicate inside phagocytes in vivo. Complex regulation permits, but is also required for, bacterial replication in diverse niches, and flagellin expression serves as a model system for understanding bacterial adaptation to life in mammalian hosts. Future work in understanding the ability of to thrive in distinct ecosystems or microenvironments will be greatly served by population-based assessments of physiology, gene expression, and phenotypes that are manifestations of heterogeneity at the level of single cells.

Citation: Cookson B. 2011. Phenotypic Variation and Gene Regulation in the Pathogenesis of Infection, p 201-207. In Maloy S, Hughes K, Casadesús J (ed), The Lure of Bacterial Genetics. ASM Press, Washington, DC. doi: 10.1128/9781555816810.ch20
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Image of FIGURE 1

Host response to a facultatively intracellular pathogen. B-cell immunoglobulin and host immune cell surface receptors like TLR2, −4, and −5 detect and respond to extracellular bacteria; cytosolic innate immune receptors respond to the presence of bacterial flagellin by triggering pyroptosis (see text for details), and peptides derived from flagellin and other antigens presented in the context of host immune cell MHC surface receptors provide stimulatory antigen for T cells.

Citation: Cookson B. 2011. Phenotypic Variation and Gene Regulation in the Pathogenesis of Infection, p 201-207. In Maloy S, Hughes K, Casadesús J (ed), The Lure of Bacterial Genetics. ASM Press, Washington, DC. doi: 10.1128/9781555816810.ch20
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Image of FIGURE 2

Bistable gene expression among individual bacteria in a genetically identical population.

Citation: Cookson B. 2011. Phenotypic Variation and Gene Regulation in the Pathogenesis of Infection, p 201-207. In Maloy S, Hughes K, Casadesús J (ed), The Lure of Bacterial Genetics. ASM Press, Washington, DC. doi: 10.1128/9781555816810.ch20
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