A Highly Conserved Bacterial D-Serine Uptake System Links Host Metabolism and Virulence

        James P. R. Connolly, Mads Gabrielsen, Robert J. Goldstone, Rhys Grinter, Dai Wang, Richard J. Cogdell, Daniel Walker, David G. E. Smith, Andrew J. Roe

PLoS Pathog.12: e1005359. Jan. 4, 2016

Speaker: Meng-Ju Tsai (蔡孟儒)                                                  Time: 14:00~15:00, Mar. 09, 2016

Commentator: Dr. I-Hsiu Huang (黃一修老師)                  Place: Room 601

Abstract:

Escherichia coli is a Gram-negative bacterial species that has numerous pathogenic forms and can be classified according to the infection site of the body, such as enterohaemorrhagic E. coli (EHEC) and urinary tract pathogenic E. coli (UPEC). EHEC possesses a large pathogenicity island, called the locus of enterocyte effacement (LEE), that encodes the type III secretion system (T3SS) for attachment/effacement (AE) lesion formation in the host cells.^[1] The authors have previoiusy reported that the host metabolite D-serine could selectively inhibit the expression of LEE-encoded T3SS in EHEC.^[2] However, how D-serine is sensed by EHEC remained obscure. In this study, the authors identified two highly conserved genes, yhaO (annotated as a D-serine inner membrane transporter) and yhaJ (annotated as a LysR-type transcriptional regulator), as ones of the most significantly upregulated genes in a LEE-overexpresssing EHEC strain. Using SDS- polyacrylamide gel electrophoresis and immunoblot analyses, they found that the production of EspD and EspA, members of T3SS in EHEC, were reduced in the ΔyhaO and ΔyhaJ mutants, and these mutants formed significantly fewer pedestals than the wild-type strain. In addition, compared to the wild-type strain, deletion of yhaO or yhaJ resulted in 45 commonly downregulated genes under LEE-inducing conditions, and 38 of them were LEE-associated. They finally showed that YhaJ coould specifically bind to the upstream region of yhaO to regulate its expression, and also could activate LEE1 transcription though binding to its promoter 1, but not promoter 2. Taken together, the authors suggested that YhaO of EHEC might be important for the microorganism to search for an appropriate environment through transporting the extracelluar D-serine into the bacterial cell.

References:

1. McDaniel TK, Jarvis KG, Donnenberg MS, Kaper JB (1995) A genetic locus of enterocyte effacement conserved among diverse enterobacterial pathogens. Proc Natl Acad Sci U S A 92: 1664–1668.
2. Connolly JPR, Goldstone RJ, Burgess K, Cogdell RJ, Beatson SA, et al. (2015) The host metabolite Dserine contributes to bacterial niche specificity through gene selection. ISME J 9: 1039–1051.