Carbapenem resistance in cystic fibrosis strains of Pseudomonas aeruginosa as a result of amino acid substitutions in porin OprD

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TitreCarbapenem resistance in cystic fibrosis strains of Pseudomonas aeruginosa as a result of amino acid substitutions in porin OprD
Type de publicationJournal Article
Year of Publication2015
AuteursRichardot C, Plesiat P, Fournier D, Monlezun L, Broutin I, Llanes C
JournalINTERNATIONAL JOURNAL OF ANTIMICROBIAL AGENTS
Volume45
Pagination529-532
Date PublishedMAY
Type of ArticleArticle
ISSN0924-8579
Mots-clésCarbapenem resistance, Cystic fibrosis, OprD porin, Pseudomonas aeruginosa
Résumé

The aim of this work was to investigate the impact of single amino acid substitutions occurring in specific porin OprD on carbapenem resistance of cystic fibrosis (CF) strains of Pseudomonas aeruginosa. A PAO1 Delta oprD mutant was complemented with the oprD genes from five carbapenem-resistant CF strains exhibiting very low amounts of mutated OprD porins in their outer membrane despite wild-type levels of oprD transcripts. Compared with wild-type porin from strain PAO1, single amino acid substitutions S403P (in periplasmic loop 8), Y242H, S278P and L345P (in p-sheets 10,12 and 14, respectively) were found to result in reduced amounts of OprD in the outer membrane, increased carbapenem resistance, and slower growth in minimal medium containing gluconate, an OprD substrate, as the sole source of carbon and energy. This indicates that in CF strains of P. aeruginosa, loss of porin OprD may not only result from mutations downregulating the expression of or disrupting the oprD gene, but also from mutations generating deleterious amino acid substitutions in the porin structure. (C) 2015 Elsevier B.V. and the International Society of Chemotherapy. All rights reserved.

DOI10.1016/j.ijantimicag.2014.12.029