# SigE Facilitates the Adaptation of Bordetella bronchiseptica to Stress Conditions and Lethal Infection in Immunocompromised Mice

 Title: SigE Facilitates the Adaptation of Bordetella bronchiseptica to Stress Conditions and Lethal Infection in Immunocompromised Mice Author: Barchinger, Sarah E; Hester, Sara E; Harvill, Eric T; Ades, Sarah E; Zhang, Xuqing; Rodriguez, Maria E Note: Order does not necessarily reflect citation order of authors. Citation: Barchinger, Sarah E., Xuqing Zhang, Sara E. Hester, Maria E. Rodriguez, Eric T. Harvill, and Sarah E. Ades. 2012. SigE facilitates the adaptation of Bordetella bronchiseptica to stress conditions and lethal infection in immunocompromised mice. BMC Microbiology 12:179. Full Text & Related Files: 3490749.pdf (1.614Mb; PDF) Abstract: Background: The cell envelope of a bacterial pathogen can be damaged by harsh conditions in the environment outside a host and by immune factors during infection. Cell envelope stress responses preserve the integrity of this essential compartment and are often required for virulence. Bordetella species are important respiratory pathogens that possess a large number of putative transcription factors. However, no cell envelope stress responses have been described in these species. Among the putative Bordetella transcription factors are a number of genes belonging to the extracytoplasmic function (ECF) group of alternative sigma factors, some of which are known to mediate cell envelope stress responses in other bacteria. Here we investigate the role of one such gene, sigE, in stress survival and pathogenesis of Bordetella bronchiseptica. Results: We demonstrate that sigE encodes a functional sigma factor that mediates a cell envelope stress response. Mutants of B. bronchiseptica strain RB50 lacking sigE are more sensitive to high temperature, ethanol, and perturbation of the envelope by SDS-EDTA and certain $$\beta$$-lactam antibiotics. Using a series of immunocompromised mice deficient in different components of the innate and adaptive immune responses, we show that SigE plays an important role in evading the innate immune response during lethal infections of mice lacking B cells and T cells. SigE is not required, however, for colonization of the respiratory tract of immunocompetent mice. The sigE mutant is more efficiently phagocytosed and killed by peripheral blood polymorphonuclear leukocytes (PMNs) than RB50, and exhibits decreased cytotoxicity toward macrophages. These altered interactions with phagocytes could contribute to the defects observed during lethal infection. Conclusions: Much of the work on transcriptional regulation during infection in B. bronchiseptica has focused on the BvgAS two-component system. This study reveals that the SigE regulon also mediates a discrete subset of functions associated with virulence. SigE is the first cell envelope stress-sensing system to be described in the bordetellae. In addition to its role during lethal infection of mice deficient in adaptive immunity, our results indicate that SigE is likely to be important for survival in the face of stresses encountered in the environment between hosts. Published Version: doi:10.1186/1471-2180-12-179 Other Sources: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3490749/pdf/ Terms of Use: This article is made available under the terms and conditions applicable to Other Posted Material, as set forth at http://nrs.harvard.edu/urn-3:HUL.InstRepos:dash.current.terms-of-use#LAA Citable link to this page: http://nrs.harvard.edu/urn-3:HUL.InstRepos:10579387 Downloads of this work: