title: Community behavior and spatial regulation within a bacterial microcolony in deep tissue sites serves to protect against host attack.
abstract: 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.
authors.affiliation: Howard Hughes Medical Institute, Sackler School of Graduate Biomedical Science, Tufts University School of Medicine, 150 Harrison Avenue, Boston, MA 02111, USA; Department of Molecular Biology and Microbiology, Sackler School of Graduate Biomedical Science, Tufts University School of Medicine, 150 Harrison Avenue, Boston, MA 02111, USA.
authors.forename: Kimberly M
authors.initials: KM
authors.lastname: Davis
authors.affiliation: Howard Hughes Medical Institute, Sackler School of Graduate Biomedical Science, Tufts University School of Medicine, 150 Harrison Avenue, Boston, MA 02111, USA; Department of Molecular Biology and Microbiology, Sackler School of Graduate Biomedical Science, Tufts University School of Medicine, 150 Harrison Avenue, Boston, MA 02111, USA; Graduate Program in Molecular Microbiology, Sackler School of Graduate Biomedical Science, Tufts University School of Medicine, 150 Harrison Avenue, Boston, MA 02111, USA.
authors.forename: Sina
authors.initials: S
authors.lastname: Mohammadi
authors.affiliation: Howard Hughes Medical Institute, Sackler School of Graduate Biomedical Science, Tufts University School of Medicine, 150 Harrison Avenue, Boston, MA 02111, USA; Department of Molecular Biology and Microbiology, Sackler School of Graduate Biomedical Science, Tufts University School of Medicine, 150 Harrison Avenue, Boston, MA 02111, USA. Electronic address: ralph.isberg@tufts.edu.
authors.forename: Ralph R
authors.initials: RR
authors.lastname: Isberg
mesh_terms: D000818:Animals; D004195:Disease Models, Animal; D005260:Female; D054884:Host-Pathogen Interactions; D057131:Immune Evasion; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D009504:Neutrophils / Q000276:immunology / Q000382:microbiology; D009569:Nitric Oxide / Q000378:metabolism / Q000633:toxicity; D013154:Spleen / Q000382:microbiology; D015011:Yersinia pseudotuberculosis / Q000254:growth & development / Q000276:immunology* / Q000502:physiology*; D015012:Yersinia pseudotuberculosis Infections / Q000276:immunology* / Q000473:pathology*
chemical_list: D009569:Nitric Oxide