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Pseudomonas aeruginosa has different resistant mechanisms including the constitutive MexAB-OprM efflux pump. Single nucleotide polymorphisms (SNPs) in the mexR, nalC, and nalD repressors of this efflux pump can contribute to antimicrobial resistance; however, it is unknown whether these changes are mainly related to genetic lineages or environmental pressure. This study identifies SNPs in the mexR, nalC, and nalD genes in clinical and environmental isolates of P. aeruginosa (including high-risk clones). Ninety-one P. aeruginosa strains were classified according to their resistance to antibiotics, typified by multilocus sequencing, and mexR, nalC, and nalD genes sequenced for SNPs identification. The mexAB-oprM transcript expression was determined. The 96.7% of the strains were classified as multidrug resistant. Eight strains produced serine carbapenemases, and 11 strains metallo-β-lactamases. Twenty-three new STs and high-risk clones ST111 and ST233 were identified. SNPs in the mexR, nalC, and nalD genes revealed 27 different haplotypes (patterns). Sixty-two mutational changes were identified, 13 non-synonymous. Haplotype 1 was the most frequent (n = 40), and mainly identified in strains ST1725 (33/40), with 57.5% pan drug resistant strains, 36.5% extensive drug resistant and two strains exhibiting serin-carbapenemases. Haplotype 12 (n = 9) was identified in ST233 and phylogenetically related STs, with 100% of the strains exhibiting XDR and 90% producing metallo-β-lactamases. Haplotype 5 was highly associated with XDR and related to dead when compared to ST1725 and ST233 (RRR 23.34; p = 0.009 and RRR 32.01; p = 0.025). A significant relationship between the mexR-nalC-nalD haplotypes and phylogenetically related STs was observed, suggesting mutational changes in these repressors are highly maintained within genetic lineages. In addition, phylogenetically related STs showed similar resistant profiles; however, the resistance was (likely or partly) attributed to the MexAB-OprM efflux pump in 56% of the strains (only 45.05% showed mexA overtranscription), in the remaining strains the resistance could be attributed to carbapenemases or mechanisms including other pumps, since same SNPs in the repressor genes gave rise to different resistance profiles.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9089866 | PMC |
http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0266742 | PLOS |
Microbiol Spectr
December 2024
UMR CNRS 6249 Chrono-Environnement, UFR Santé, Université Bourgogne Franche-Comté, Besançon, France.
Exposure of to cinnamaldehyde (CNA), a natural electrophilic antimicrobial often used as self-medication to treat mild infections, triggers overproduction of the MexAB-OprM efflux system, leading to multidrug resistance. In this study, we demonstrate that CNA exposure induces expression of genes regulated by the two-component system AmgRS. AmgRS activates MexAB-OprM production, independent of repressors MexR and NalD.
View Article and Find Full Text PDFFront Cell Infect Microbiol
June 2024
Laboratory of Microbiology, Department of Clinical Laboratories; Escuela de Medicina, Pontificia Universidad Católica de Chile, Santiago, Chile.
Introduction: Ceftazidime/avibactam (CZA) is indicated against multidrug-resistant , particularly those that are carbapenem resistant. CZA resistance in producing PER, a class A extended-spectrum β-lactamase, has been well documented . However, data regarding clinical isolates are scarce.
View Article and Find Full Text PDFBMC Microbiol
May 2024
Department of Botany and Microbiology, Faculty of Science, Menoufia University, Shebin El- Kom, Egypt.
Background: Pseudomonas aeruginosa is an opportunistic pathogen responsible for complicated UTIs and exhibits high antibiotic resistance, leading to increased mortality rates, especially in cases of multidrug-resistant strains. This study aimed to investigate the antibiotic susceptibility patterns and genomic characterization of XDR strains identified in end-stage liver disease patients who underwent liver transplants.
Methods: In this study, a number of 30 individuals who underwent liver transplants were registered.
Microorganisms
April 2024
Faculty of Medicine, University of Thessaly, 41500 Larissa, Greece.
To date, three carbapenem resistance mechanisms have been identified: carbapenemase released from the pathogen, changes in the expression of the outer membrane OprD porin, and overexpression of the efflux pump MexAB-OprM. Twelve carbapenemase-negative carbapenem-resistant strains, isolated from patients hospitalized at the University Hospital of Larissa, Central Greece, during 2023, which belonged to various sequence types (STs), were selected and were studied focusing on the characterization of their -lactamases, on changes to OprD and its regulator MexT proteins, and on alterations to the MexAB-OprM regulator proteins encoded by the , , and genes. Whole genome sequencing analysis revealed the presence of -lactamase encoding genes, with present in all isolates.
View Article and Find Full Text PDFAntimicrob Agents Chemother
May 2024
Antimicrobial Resistance Research Center, National Institute of Infectious Diseases, Higashimurayama, Tokyo, Japan.
Japan is a country with an approximate 10% prevalence rate of carbapenem-resistant (CRPA). Currently, a comprehensive overview of the genotype and phenotype patterns of CRPA in Japan is lacking. Herein, we conducted genome sequencing and quantitative antimicrobial susceptibility testing for 382 meropenem-resistant CRPA isolates that were collected from 78 hospitals across Japan from 2019 to 2020.
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