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Proteobactin and a yersiniabactin‐related siderophore mediate iron acquisition in Proteus mirabilis
Author(s) -
Himpsl Stephanie D.,
Pearson Melanie M.,
Arewång Carl J.,
Nusca Tyler D.,
Sherman David H.,
Mobley Harry L. T.
Publication year - 2010
Publication title -
molecular microbiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.857
H-Index - 247
eISSN - 1365-2958
pISSN - 0950-382X
DOI - 10.1111/j.1365-2958.2010.07317.x
Subject(s) - siderophore , proteus mirabilis , biology , microbiology and biotechnology , virulence , gene , escherichia coli , genetics
Summary Proteus mirabilis causes complicated urinary tract infections (UTIs). While the urinary tract is an iron‐limiting environment, iron acquisition remains poorly characterized for this uropathogen. Microarray analysis of P. mirabilis HI4320 cultured under iron limitation identified 45 significantly upregulated genes ( P ≤ 0.05) that represent 21 putative iron‐regulated systems. Two gene clusters, PMI0229‐0239 and PMI2596‐2605, encode putative siderophore systems. PMI0229‐0239 encodes a non‐ribosomal peptide synthetase‐independent siderophore system for producing a novel siderophore, proteobactin. PMI2596‐2605 are contained within the high‐pathogenicity island, originally described in Yersinia pestis , and encodes proteins with apparent homology and organization to those involved in yersiniabactin production and uptake. Cross‐feeding and biochemical analysis shows that P. mirabilis is unable to utilize or produce yersiniabactin, suggesting that this yersiniabactin‐related locus is functionally distinct. Only disruption of both systems resulted in an in vitro iron‐chelating defect; demonstrating production and iron‐chelating activity for both siderophores. These findings clearly show that proteobactin and the yersiniabactin‐related siderophore function as iron acquisition systems. Despite the activity of both siderophores, only mutants lacking the yersiniabactin‐related siderophore have reduced fitness in vivo . The fitness requirement for the yersiniabactin‐related siderophore during UTI shows, for the first time, the importance of siderophore production in vivo for P. mirabilis .