TY - JOUR
T1 - Community Behavior and Spatial Regulation within a Bacterial Microcolony in Deep Tissue Sites Serves to Protect against Host Attack
AU - Davis, Kimberly M.
AU - Mohammadi, Sina
AU - Isberg, Ralph R.
N1 - Funding Information:
We thank the following members of R.R.I.’s lab for their help in preparing this manuscript: Andrew Hempstead, Dennise de Jésus, Caitlin Liu, Dervla Isaac, Won-Young Choi, Edward Geisinger, and Seble Asrat. We also thank Joan Mecsas and the members of her laboratory for advice and constant feedback throughout all stages of the work. H&E-stained sections were generated with the help of the Tufts Animal Histology Core. R.R.I. is an Investigator of HHMI. This work was supported by NIAID awards 2R56AI023538 and R21AI097728, as well as by an American Cancer Society-Ellison Foundation Postdoctoral Fellowship (PF-13-360-01-MPC).
Publisher Copyright:
© 2015 Elsevier Inc.
PY - 2015/1/14
Y1 - 2015/1/14
N2 - Bacterial pathogens express virulence-specific transcriptional programs that allow tissue colonization. Although phenotypic variation has been noted in the context of antibiotic exposure, no direct evidence exists for heterogeneity in virulence-specific transcriptional programs within tissues. In a mouse model of Yersinia pseudotuberculosis infection, we show that at least three subpopulations of bacteria develop within a single tissue site in response to distinct host signals. Bacteria growing on the exterior of spleen microcolonies responded to soluble signals and induced the nitric oxide (NO)-detoxifying gene, hmp. Hmp effectively eliminated NO diffusion and protected the interior bacterial population from exposure to NO-derived inducing signals. A third subpopulation, constituting the most peripherally localized bacteria, directly contacted neutrophils and transcriptionally upregulated a virulence factor. These studies demonstrate that growth within tissues results in transcriptional specialization within a single focus of microbial replication, facilitating directed pathogen counterattack against the host response.
AB - Bacterial pathogens express virulence-specific transcriptional programs that allow tissue colonization. Although phenotypic variation has been noted in the context of antibiotic exposure, no direct evidence exists for heterogeneity in virulence-specific transcriptional programs within tissues. In a mouse model of Yersinia pseudotuberculosis infection, we show that at least three subpopulations of bacteria develop within a single tissue site in response to distinct host signals. Bacteria growing on the exterior of spleen microcolonies responded to soluble signals and induced the nitric oxide (NO)-detoxifying gene, hmp. Hmp effectively eliminated NO diffusion and protected the interior bacterial population from exposure to NO-derived inducing signals. A third subpopulation, constituting the most peripherally localized bacteria, directly contacted neutrophils and transcriptionally upregulated a virulence factor. These studies demonstrate that growth within tissues results in transcriptional specialization within a single focus of microbial replication, facilitating directed pathogen counterattack against the host response.
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U2 - 10.1016/j.chom.2014.11.008
DO - 10.1016/j.chom.2014.11.008
M3 - Article
C2 - 25500192
AN - SCOPUS:84920869177
VL - 17
SP - 21
EP - 31
JO - Cell Host and Microbe
JF - Cell Host and Microbe
SN - 1931-3128
IS - 1
ER -