Host-Derived Metabolites Modulate Transcription of <i>Salmonella</i> Genes Involved in l-Lactate Utilization during Gut Colonization.

Gillis, Caroline C; Winter, Maria G; Chanin, Rachael B; Zhu, Wenhan; Spiga, Luisella; Winter, Sebastian E

Host-Derived Metabolites Modulate Transcription of Salmonella Genes Involved in l-Lactate Utilization during Gut Colonization.

Gillis, Caroline C; Winter, Maria G; Chanin, Rachael B; Zhu, Wenhan; Spiga, Luisella; Winter, Sebastian E.

Afiliación

Gillis CC; Department of Microbiology, University of Texas Southwestern Medical Center, Dallas, Texas, USA.
Winter MG; Department of Microbiology, University of Texas Southwestern Medical Center, Dallas, Texas, USA.
Chanin RB; Department of Microbiology, University of Texas Southwestern Medical Center, Dallas, Texas, USA.
Zhu W; Department of Microbiology, University of Texas Southwestern Medical Center, Dallas, Texas, USA.
Spiga L; Department of Microbiology, University of Texas Southwestern Medical Center, Dallas, Texas, USA.
Winter SE; Department of Microbiology, University of Texas Southwestern Medical Center, Dallas, Texas, USA Sebastian.Winter@UTSouthwestern.edu.

Infect Immun ; 87(4)2019 04.

Article en En | MEDLINE | ID: mdl-30617205

RESUMEN

During Salmonella enterica serovar Typhimurium infection, host inflammation alters the metabolic environment of the gut lumen to favor the outgrowth of the pathogen at the expense of the microbiota. Inflammation-driven changes in host cell metabolism lead to the release of l-lactate and molecular oxygen from the tissue into the gut lumen. Salmonella utilizes lactate as an electron donor in conjunction with oxygen as the terminal electron acceptor to support gut colonization. Here, we investigated transcriptional regulation of the respiratory l-lactate dehydrogenase LldD in vitro and in mouse models of Salmonella infection. The two-component system ArcAB repressed transcription of l-lactate utilization genes under anaerobic conditions in vitro The ArcAB-mediated repression of lldD transcription was relieved under microaerobic conditions. Transcription of lldD was induced by l-lactate but not d-lactate. A mutant lacking the regulatory protein LldR failed to induce lldD transcription in response to l-lactate. Furthermore, the lldR mutant exhibited reduced transcription of l-lactate utilization genes and impaired fitness in murine models of infection. These data provide evidence that the host-derived metabolites oxygen and l-lactate serve as cues for Salmonella to regulate lactate oxidation metabolism on a transcriptional level.

Asunto(s)

Mucosa Intestinal/microbiología; Ácido Láctico/metabolismo; Infecciones por Salmonella/metabolismo; Salmonella typhimurium/crecimiento & desarrollo; Salmonella typhimurium/metabolismo; Animales; Proteínas Bacterianas/genética; Proteínas Bacterianas/metabolismo; Femenino; Regulación Bacteriana de la Expresión Génica; Humanos; Mucosa Intestinal/metabolismo; L-Lactato Deshidrogenasa/genética; L-Lactato Deshidrogenasa/metabolismo; Masculino; Ratones; Ratones Endogámicos C57BL; Oxígeno/metabolismo; Infecciones por Salmonella/microbiología; Salmonella typhimurium/enzimología; Salmonella typhimurium/genética; Factores de Transcripción/genética; Factores de Transcripción/metabolismo

Palabras clave

Salmonella; gut inflammation; microbiome

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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Infecciones por Salmonella / Salmonella typhimurium / Ácido Láctico / Mucosa Intestinal Tipo de estudio: Prognostic_studies Límite: Animals / Female / Humans / Male Idioma: En Revista: Infect Immun Año: 2019 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: Estados Unidos

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