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Raghavan V.,Yale University | Raghavan V.,Yale Microbial science Institute | Groisman E.A.,Yale University | Groisman E.A.,Yale Microbial science Institute | Groisman E.A.,Howard Hughes Medical Institute
Journal of Bacteriology | Year: 2015

The mammalian intestine provides nutrients to hundreds of bacterial species. Closely related species often harbor homologous nutrient utilization genes and cocolonize the gut, raising questions regarding the strategies mediating their stable coexistence. Here we reveal that related Bacteroides species that can utilize the mammalian glycan chondroitin sulfate (CS) have diverged in the manner in which they temporally regulate orthologous CS utilization genes. Whereas certain Bacteroides species display a transient surge in CS utilization transcripts upon exposure to CS, other species exhibit sustained activation of these genes. Remarkably, species-specific expression dynamics are retained even when the key players governing a particular response are replaced by those from a species with a dissimilar response. Bacteroides species exhibiting distinct expression behaviors in the presence of CS can be cocultured on CS. However, they vary in their responses to CS availability and to the composition of the bacterial community when CS is the sole carbon source. Our results indicate that diversity resulting from regulation of polysaccharide utilization genes may enable the coexistence of gut bacterial species using a given nutrient. © 2015, American Society for Microbiology.

Pontes M.H.,Howard Hughes Medical Institute | Pontes M.H.,Yale University | Pontes M.H.,Yale Microbial science Institute | Sevostyanova A.,Yale University | And 3 more authors.
Journal of Molecular Biology | Year: 2015

Abstract Adenosine triphosphate (ATP) is the energy currency of living cells. Even though ATP powers virtually all energy-dependent activities, most cellular ATP is utilized in protein synthesis via tRNA aminoacylation and guanosine triphosphate regeneration. Magnesium (Mg2+), the most common divalent cation in living cells, plays crucial roles in protein synthesis by maintaining the structure of ribosomes, participating in the biochemistry of translation initiation and functioning as a counterion for ATP. A non-physiological increase in ATP levels hinders growth in cells experiencing Mg2+ limitation because ATP is the most abundant nucleotide triphosphate in the cell, and Mg2+ is also required for the stabilization of the cytoplasmic membrane and as a cofactor for essential enzymes. We propose that organisms cope with Mg2+ limitation by decreasing ATP levels and ribosome production, thereby reallocating Mg2+ to indispensable cellular processes. © 2015 Elsevier Ltd. All rights reserved.

Pontes M.H.,Howard Hughes Medical Institute | Pontes M.H.,Yale University | Pontes M.H.,Yale Microbial science Institute | Lee E.-J.,Howard Hughes Medical Institute | And 8 more authors.
Proceedings of the National Academy of Sciences of the United States of America | Year: 2015

Cellulose is the most abundant organic polymer on Earth. In bacteria, cellulose confers protection against environmental insults and is a constituent of biofilms typically formed on abiotic surfaces. We report that, surprisingly, Salmonella enterica serovar Typhimurium makes cellulose when inside macrophages. We determine that preventing cellulose synthesis increases virulence, whereas stimulation of cellulose synthesis inside macrophages decreases virulence. An attenuated mutant lacking the mgtC gene exhibited increased cellulose levels due to increased expression of the cellulose synthase gene bcsA and of cyclic diguanylate, the allosteric activator of the BcsA protein. Inactivation of bcsA restored wild-type virulence to the Salmonella mgtC mutant, but not to other attenuated mutants displaying a wild-type phenotype regarding cellulose. Our findings indicate that a virulence determinant can promote pathogenicity by repressing a pathogen's antivirulence trait. Moreover, they suggest that controlling antivirulence traits increases long-term pathogen fitness by mediating a trade-off between acute virulence and transmission. © 2015, National Academy of Sciences. All rights reserved.

Park S.-Y.,Howard Hughes Medical Institute | Park S.-Y.,Yale Microbial science Institute | Pontes M.H.,Howard Hughes Medical Institute | Pontes M.H.,Yale Microbial science Institute | And 2 more authors.
Proceedings of the National Academy of Sciences of the United States of America | Year: 2015

Flagella are multiprotein complexes necessary for swimming and swarming motility. In Salmonella enterica serovar Typhimurium, flagella-mediated motility is repressed by the PhoP/PhoQ regulatory system. We now report that Salmonella can move on 0.3% agarose media in a flagella-independent manner when experiencing the PhoP/PhoQ-inducing signal low Mg2+. This motility requires the PhoP-activated mgtA, mgtC, and pagM genes, which specify a Mg2+ transporter, an inhibitor of Salmonella's own F1Fo ATPase, and a small protein of unknown function, respectively. The MgtA and MgtC proteins are necessary for pagM expression because pagM mRNA levels were lower in mgtA and mgtC mutants than in wild-type Salmonella, and also because pagM expression from a heterologous promoter rescued motility in mgtA and mgtC mutants. PagMpromotes groupmotility by a surface protein(s), as a pagM-expressing strain conferred motility upon a pagM null mutant, and proteinase K treatment eliminated motility. The pagM gene is rarely found outside subspecies I of S. enterica and often present in nonfunctional allelic forms in organisms lacking the identified motility. Deletion of the pagM gene reduced bacterial replication on 0.3% agarose low Mg2+ media but not in low Mg2+ liquid media. Our findings define a form of motility that allows Salmonella to scavenge nutrients and to escape toxic compounds in low Mg2+ semisolid environments.

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