A Novel Two-Component Signaling System Facilitates Uropathogenic Escherichia coli's Ability to Exploit Abundant Host Metabolites

PLoS Pathogens

Subhashinie Kariyawasam¹  Lisa K. Nolan²  Wentong Cai²  Yvonne Wannemuehler²  Nicolle L. Barbieri²  Ganwu Li²  Bryon Nicholson²  Yaping Feng³  Giuseppe Dell'Anna⁴  Catherine M. Logue⁵ 

[1] Departamento de Biofísica, Universidade Federal do Rio Grande do Sul, Porto Alegre, Rio Grande do Sul, Brasil;Department of Veterinary Microbiology and Preventive Medicine, College of Veterinary Medicine, Iowa State University, Ames, Iowa, United States of America;Department of Veterinary and Biomedical Sciences, Pennsylvania State University, University Park, Pennsylvania, United States of America;Laboratory Animal Resources, College of Veterinary Medicine, Iowa State University, Ames, Iowa, United States of America;Laurence H. Baker Center for Bioinformatics and Biological Statistics, Iowa State University, Ames, Iowa, United States of America

关键词: Bacterial pathogens;    Urine;    Outer membrane proteins;    Anaerobic bacteria;    Oxygen;    Polymerase chain reaction;    Isl;    s;    Mammalian genomics;   

DOI  :  10.1371/journal.ppat.1003428

学科分类：生物科学（综合）

来源: Public Library of Science

【 摘 要 】

Two-component signaling systems (TCSs) are major mechanisms by which bacteria adapt to environmental conditions. It follows then that TCSs would play important roles in the adaptation of pathogenic bacteria to host environments. However, no pathogen-associated TCS has been identified in uropathogenic Escherichia coli (UPEC). Here, we identified a novel TCS, which we termed KguS/KguR (KguS: α-ketoglutarate utilization sensor; KguR: α-ketoglutarate utilization regulator) in UPEC CFT073, a strain isolated from human pyelonephritis. kguS/kguR was strongly associated with UPEC but was found only rarely among other E. coli including commensal and intestinal pathogenic strains. An in vivo competition assay in a mouse UTI model showed that deletion of kguS/kguR in UPEC CFT073 resulted in a significant reduction in its colonization of the bladders and kidneys of mice, suggesting that KguS/KguR contributed to UPEC fitness in vivo. Comparative proteomics identified the target gene products of KguS/KguR, and sequence analysis showed that TCS KguS/KguR and its targeted-genes, c5032 to c5039, are encoded on a genomic island, which is not present in intestinal pathogenic E. coli. Expression of the target genes was induced by α-ketoglutarate (α-KG). These genes were further shown to be involved in utilization of α-KG as a sole carbon source under anaerobic conditions. KguS/KguR contributed to the regulation of the target genes with the direct regulation by KguR verified using an electrophoretic mobility shift assay. In addition, oxygen deficiency positively modulated expression of kguS/kguR and its target genes. Taken altogether, this study describes the first UPEC-associated TCS that functions in controlling the utilization of α-ketoglutarate in vivo thereby facilitating UPEC adaptation to life inside the urinary tract.

【 授权许可】

CC BY