Amino Acid Substitutions Account for Most MexS Alterations in Clinical nfxC Mutants of Pseudomonas aeruginosa

Antimicrobial Agents and Chemotherapy
Charlotte RichardotC Llanes

Abstract

Multidrug-resistant mutants ofPseudomonas aeruginosathat overproduce the active efflux system MexEF-OprN (callednfxCmutants) have rarely been characterized in the hospital setting. Screening of 221 clinical strains exhibiting a reduced susceptibility to ciprofloxacin (a substrate of MexEF-OprN) and imipenem (a substrate of the negatively coregulated porin OprD) led to the identification of 43 (19.5%)nfxCmutants. Subsequent analysis of 22 nonredundant mutants showed that, in contrast to theirin vitro-selected counterparts, only 3 of them (13.6%) harbored a disruptedmexSgene, which codes for the oxidoreductase MexS, whose inactivation is known to activate themexEF-oprNoperon through a LysR-type regulator, MexT. Nine (40.9%) of the clinicalnfxCmutants contained single amino acid mutations in MexS, and these were associated with moderate effects on resistance and virulence factor production in 8/9 strains. Finally, the remaining 10 (45.5%)nfxCmutants did not display mutations in any of the regulators known to controlmexEF-oprNexpression (themexS,mexT,mvaT, andampRgenes), confirming that other loci are responsible for pump upregulation in patients. Collectively, these data demonstrate thatnfxCmutants are probably more frequent in th...Continue Reading

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Citations

Sep 14, 2016·Drug Resistance Updates : Reviews and Commentaries in Antimicrobial and Anticancer Chemotherapy·Sara Hernando-AmadoJosé L Martínez
Jan 4, 2019·Journal of Medical Microbiology·Attika RehmanIain L Lamont
Jul 31, 2019·Journal of Bacteriology·Ian T HillSimon L Dove
Aug 7, 2019·Antimicrobial Agents and Chemotherapy·Alexandre TetardCatherine Llanes
Nov 9, 2018·Scientific Reports·Gertrudis HornaJoaquim Ruiz
Jul 5, 2018·Frontiers in Molecular Biosciences·Karim Housseini B IssaIsabelle Broutin
Oct 17, 2017·Frontiers in Microbiology·Marisa HaenniKaty Jeannot
Mar 13, 2021·Scientific Reports·Syed A K Shifat AhmedJames S G Dooley
May 12, 2021·Journal of Bacteriology·Samuel LeeColin Manoil
Jul 13, 2021·Frontiers in Microbiology·Zhenzhen MaYongxin Jin

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