Enterobacteria secrete an inhibitor of Pseudomonas virulence during clinical bacteriuria

Shannon I. Ohlemacher, Daryl E. Giblin, D. André D'Avignon, Ann E. Stapleton, Barbara W. Trautner, Jeffrey P. Henderson

Research output: Contribution to journalArticlepeer-review

26 Scopus citations


Escherichia coli and other Enterobacteriaceae are among the most common pathogens of the human urinary tract. Among the genetic gains of function associated with urinary E. coli isolates is the Yersinia high pathogenicity island (HPI), which directs the biosynthesis of yersiniabactin (Ybt), a virulence-associated metallophore. Using a metabolomics approach, we found that E. coli and other Enterobacteriaceae expressing the Yersinia HPI also secrete escherichelin, a second metallophore whose chemical structure matches a known synthetic inhibitor of the virulence-associated pyochelin siderophore system in Pseudomonas aeruginosa. We detected escherichelin during clinical E. coli urinary tract infection (UTI) and experimental human colonization with a commensal, potentially probiotic E. coli bacteriuria strain. Escherichelin production by colonizing enterobacteria may help human hosts resist opportunistic infections by Pseudomonas and other pyochelin-expressing bacteria. This siderophore-based mechanism of microbial antagonism may be one of many elements contributing to the protective effects of the human microbiome. Future UTI-preventive probiotic strains may benefit by retaining the escherichelin biosynthetic capacity of the Yersinia HPI while eliminating the Ybt biosynthetic capacity.

Original languageEnglish (US)
Pages (from-to)4018-4030
Number of pages13
JournalJournal of Clinical Investigation
Issue number11
StatePublished - Nov 1 2017

Bibliographical note

Funding Information:
We thank Chloe Pinkner, Jan Crowley, and Hung Tran at Washington University for their technical assistance. JPH holds a Career Award for Medical Scientists from the Burroughs Wellcome Fund and acknowledges receiving grants from the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) (R01DK099534 and R56DK111930) and a Prevention Epicenters Grant from the Centers for Disease Control and Prevention (CDC U54CK000482). SIO is supported by a training grant from the National Institute of Allergy and Infectious Diseases (5T32AI007172-35) and the Graduate Research Fellowship Program (DGE-1143954) from the National Science Foundation (NSF). Computations were supported by a grant from the United States Public Health Service (P41-RR00954); some computations were performed at the Washington University Center for High Performance Computing and the Washington University Computational Chemistry Facility, funded by a grant from the NSF (CHE-0443501). The high-resolution MS performed in this project was supported by a grant from the National Institute of General Medical Sciences (8 P41 GM103422) from the NIH. The P. aeruginosa transposon mutant PW5011 was obtained from the Manoil laboratory at the University of Washington (NIH grant P30 DK089507). Specimens from patients with uncomplicated UTI were obtained with support from NIH grant P50DK064540. Experimental patient colonization studies were supported by a grant from the NIDDK, NIH (R21 DK092293) and by resources of the Houston VA Center for Innovations in Quality, Effectiveness, and Safety (CIN13-413) at the Michael E. DeBakey Veterans Affairs Medical Center. The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.


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