RESUMO
Yersinia pestis has a flea-mammal-flea transmission cycle, and is a zoonotic pathogen that causes the systemic diseases bubonic and septicaemic plague in rodents and humans, as well as pneumonic plague in humans and non-human primates. Bubonic and pneumonic plague are quite different diseases that result from different routes of infection. Manganese (Mn) acquisition is critical for the growth and pathogenesis of a number of bacteria. The Yfe/Sit and/or MntH systems are the two prominent Mn transporters in Gram-negative bacteria. Previously we showed that the Y. pestis Yfe system transports Fe and Mn. Here we demonstrate that a mutation in yfe or mntH did not significantly affect in vitro aerobic growth under Mn-deficient conditions. A yfe mntH double mutant did exhibit a moderate growth defect which was alleviated by supplementation with Mn. No short-term energy-dependent uptake of (54)Mn was observed in this double mutant. Like the yfeA promoter, the mntH promoter was repressed by both Mn and Fe via Fur. Sequences upstream of the Fur binding sequence in the yfeA promoter converted an iron-repressible promoter to one that is also repressed by Mn and Fe. To our knowledge, this is the first report identifying cis promoter elements needed to alter cation specificities involved in transcriptional repression. Finally, the Y. pestis yfe mntH double mutant had an ~133-fold loss of virulence in a mouse model of bubonic plague but no virulence loss in the pneumonic plague model. This suggests that Mn availability, bacterial Mn requirements or Mn transporters used by Y. pestis are different in the lungs (pneumonic plague) compared with systemic disease.
Assuntos
Proteínas de Bactérias/metabolismo , Proteínas de Transporte de Cátions/metabolismo , Regulação Bacteriana da Expressão Gênica , Proteínas de Membrana Transportadoras/metabolismo , Proteínas Repressoras/metabolismo , Fatores de Virulência/metabolismo , Yersinia pestis/metabolismo , Yersinia pestis/patogenicidade , Animais , Fusão Gênica Artificial , Proteínas de Bactérias/genética , Proteínas de Transporte de Cátions/genética , Modelos Animais de Doenças , Deleção de Genes , Genes Reporter , Humanos , Manganês/metabolismo , Proteínas de Membrana Transportadoras/genética , Camundongos , Peste/microbiologia , Peste/patologia , Regiões Promotoras Genéticas , Análise de Sobrevida , Virulência , Fatores de Virulência/genética , Yersinia pestis/genética , Yersinia pestis/crescimento & desenvolvimento , beta-Galactosidase/análise , beta-Galactosidase/genéticaRESUMO
Relying on data derived from medical records of past visits to a physician, patients' charts were examined to evaluate the effectiveness of a single nutrition counseling session provided by the same registered dietitian in improving outcome measures for patients with type 2 diabetes mellitus or cardiovascular disease. This was a retrospective study of 175 patients' charts from which laboratory data were extracted before and at 3 months after seeing the dietitian. Records were categorized into two groups based on whether the patient had attended or not attended a single nutrition counseling session. At 3 months, the group that received the nutrition counseling had statistically significant improvements in blood values and body mass index compared with the group that did not receive nutrition counseling. This study further confirms the value of a single nutrition counseling session as an effective approach to treating type 2 diabetes and cardiovascular disease.