Actively secreted iron chelating agents termed siderophores play an important role in the virulence and rhizosphere competence of fluorescent pseudomonads, including Pseudomonas aeruginosa which secretes a high affinity siderophore, pyoverdine, and the low affinity siderophore, pyochelin. Uptake of the iron-siderophore complexes is an active process that requires specific outer membrane located receptors, which are dependent of the inner membrane-associated protein TonB and two other inner membrane proteins, ExbB and ExbC. P. aeruginosa is also capable of using a remarkable variety of heterologous siderophores as sources of iron, apparently by expressing their cognate receptors. Illustrative of this feature are the 32 (of which 28 putative) siderophore receptor genes observed in the P. aeruginosa PAO1 genome. However, except for a few (pyoverdine, pyochelin, enterobactin), the vast majority of P. aeruginosa siderophore receptor genes still remain to be characterized. Ten synthetic iron chelators of catecholate type stimulated growth of a pyoverdine/pyochelin deficient P. aeruginosa PAO1 mutant under condition of severe iron limitation. Null mutants of the 32 putative TonB-dependent siderophore receptor encoding genes engineered in the same genetic background were screened for obvious deficiencies in uptake of the synthetic siderophores, but none showed decreased growth stimulation in the presence of the different siderophores. However, a double knock-out mutant of ferrienterobactin receptor encoding gene pfeA (PA 2688) and pirA (PA0931) failed to be stimulated by 4 of the tested synthetic catecholate siderophores whose chemical structures resemble enterobactin. Ferric-enterobactin also failed to stimulate growth of the double pfeA-pirA mutant although, like its synthetic analogues, it stimulated growth of the corresponding single mutants. Hence, we confirmed that pirA represents a second P. aeruginosa ferric-enterobactin receptor. The example of these two enterobactin receptors probably illustrates a more general phenomenon of siderophore receptor redundancy in P. aeruginosa.
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http://dx.doi.org/10.1016/j.femsle.2005.04.010 | DOI Listing |
Front Microbiol
December 2024
Department of Biomedical Sciences, Humanitas University, Milan, Italy.
is a significant public health concern due to the emergence of antibiotic-resistant strains. Cefiderocol (FDC), a novel siderophore cephalosporin, has shown promise as a last-line treatment for multidrug-resistant Gram-negative bacteria. However, the emergence of -acquired FDC-resistant strains highlights the need for advanced tools to identify resistance-associated genomic mutations and address the challenges of FDC susceptibility testing.
View Article and Find Full Text PDFBiochemistry
January 2025
Department of Chemistry, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, United States.
The pathogen-associated -glucosyltransferase IroB is involved in the biosynthesis of salmochelins, -glucosylated derivatives of enterobactin (Ent), which is a triscatecholate siderophore of enteric bacteria including and . Here, we reassess the ability of IroB to -glucosylate non-native triscatecholate mimics of Ent, which may have utility in the design and development of siderophore-based therapeutics and diagnostics. We establish TRENCAM (TC) and MECAM (MC), synthetic Ent analogs with tris(2-aminoethyl)amine- or mesitylene-derived backbones replacing the trilactone core of Ent, respectively, and their monoglucosylated congeners as substrates of IroB.
View Article and Find Full Text PDFCefiderocol (FDC), a siderophore-cephalosporin conjugate, is the newest option for treating infection with carbapenem-resistant gram-negative bacteria. We identified a novel mechanism contributing to decreased FDC susceptibility in Klebsiella pneumoniae clinical isolates. The mechanism involves 2 coresident plasmids: pKpQIL, carrying variants of bla carbapenemase gene, and pKPN, carrying the ferric citrate transport (FEC) system.
View Article and Find Full Text PDFInt J Infect Dis
November 2024
Université de Poitiers, PHAR2, Inserm U1070, Poitiers, France. Electronic address:
Ann Clin Microbiol Antimicrob
November 2024
Microbiology and Virology Unit, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milan, Italy.
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