2026-07-22T20:06:46Zhttps://repisalud.isciii.es/rest/oai/requestoai:repisalud.isciii.es:20.500.12105/166922024-11-28T12:34:58Zcom_20.500.12105_2052com_20.500.12105_2051com_20.500.12105_15322col_20.500.12105_19609col_20.500.12105_16967col_20.500.12105_25179
Repisalud
author
Perez-Vazquez, Maria
author
López-Causapé, Carla
author
Corral-Lugo, Andres
author
McConnell, Michael J
author
Oteo-Iglesias, Jesus
author
Oliver, Antonio
author
Martin-Galiano, Antonio Javier
funder
Instituto de Salud Carlos III
funder
Ministerio de Ciencia e Innovación (España)
funder
Unión Europea. Comisión Europea. NextGenerationEU
2023-11-17T11:25:57Z
2023-11-17T11:25:57Z
2023-10-04
Microorganisms. 2023 Oct 4;11(10):2486.
10.3390/microorganisms11102486
2076-2607
Microorganisms
https://hdl.handle.net/20.500.13003/20008
37894144
2-s2.0-85175064714
http://hdl.handle.net/20.500.12105/16692
1094362900001
Mutations leading to upregulation of efflux pumps can produce multiple drug resistance in the pathogen Pseudomonas aeruginosa. Changes in their DNA binding regions, i.e., palindromic operators, can compromise pump depression and subsequently enhance resistance against several antibacterials and biocides. Here, we have identified (pseudo)palindromic repeats close to promoters of genes encoding 13 core drug-efflux pumps of P. aeruginosa. This framework was applied to detect mutations in these repeats in 17,292 genomes. Eighty-nine percent of isolates carried at least one mutation. Eight binary genetic properties potentially related to expression were calculated for mutations. These included palindromicity reduction, mutation type, positioning within the repeat and DNA-bending shift. High-risk ST298, ST308 and ST357 clones commonly carried four conserved mutations while ST175 and the cystic fibrosis-linked ST649 clones showed none. Remarkably, a T-to-C transition in the fourth position of the upstream repeat for mexEF-oprN was nearly exclusive of the high-risk ST111 clone. Other mutations were associated with high-risk sublineages using sample geotemporal metadata. Moreover, 1.5% of isolates carried five or more mutations suggesting they undergo an alternative program for regulation of their effluxome. Overall, P. aeruginosa shows a wide range of operator mutations with a potential effect on efflux pump expression and antibiotic resistance.
eng
High-risk clone
Multidrug resistance
Operator
Repressor
Resistome
Mutation Analysis in Regulator DNA-Binding Regions for Antimicrobial Efflux Pumps in 17,000 Pseudomonas aeruginosa Genomes
research article
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MutationAnalysisRegulatorDNA-Binding_2023.pdf.txt
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