1. Genetic Variations in MexAB-OprM Efflux Pump Regulators and Their Association with Antibiotic Resistance and Sequence type in Clinical and Epidemiologically High-risk Clones of Pseudomonas Aeruginosa
- Author
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Rodríguez-Espino Ba, Rosas-Pérez I, Castellanos-Cruz MdC, Clavijo Ho, Zúñiga G, Rodea Ge, Cerritos R, Velazquez-Guadarrama N, Aguilar-Rodea P, Galindo Jcv, Reyes-López A, Parra-Ortega I, and Arroyo Aeg
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Antibiotic resistance ,Pseudomonas aeruginosa ,Genetic variation ,medicine ,Efflux ,Biology ,medicine.disease_cause ,Mexab oprm ,Sequence (medicine) ,Microbiology - Abstract
Background: Pseudomonas aeruginosa is a major opportunistic pathogen involved in healthcare-associated infections with high mortality rates. This bacterium exhibits elevated resistance to a wide range of antibiotics, resulting in part from the overexpression of efflux pumps, among which MexAB-OprM stands out as constitutive. Antibiotic resistance in clinical isolates is associated with mutations in the mexR, nalC, and nalD repressors that modulate the expression of this efflux pump. This study identifies point mutations in the mexR, nalC, and nalD genes and investigates their associations with antibiotic resistance and sequence type in clinical and epidemiologically high-risk clones of P. aeruginosa. Results: A total of 91 P. aeruginosa strains isolated at a pediatric hospital in Mexico (2007–2015) were classified according to their resistance to antibiotics. The strains were typed by multilocus sequencing of 7 genes. The MexAB-OprM efflux pump phenotype was determined using the minimal inhibitory concentration for the reporter antibiotic carbenicillin in the presence/absence of the efflux pump inhibitor Phe-Arg-β-naphthylamine. Sequencing of the mexR, nalC, and nalD genes to identify mutations was performed. Genetic relationship among the strains was evaluated by a phylogenetic inference analysis using maximum likelihood to construct a phylogenetic network. The relationship between variables was determined by a principal component analysis. STs revealed six main complexes. Mutations in the mexR, nalC, and nalD genes revealed 27 different haplotypes. Pan-drug and extensive drug resistant profiles were associated with specific STs with haplotypes 1 (ST1725, endemic clone), 8, 12 (ST233, epidemiologically high-risk clone), and 5 [related to dead when compared to ST1725 and ST233 (RRR 23.34; p=0.009 and RRR 32.01; p=0.025)], however the resistance in these strains was not mainly attributed to the MexAB-OprM phenotype. Strains with the same haplotype and resistant profile showed different pump behavior.Conclusions: A significant relationship between ST and resistant profiles was observed; on one hand, the mexR-nalC-nalD haplotypes were not related to the MexAB-OprM efflux pump phenotypic behavior. On the other hand, the relationship between mexR-nalC-nalD haplotypes and phylogenetically related ST, suggest mutations in these repressors are highly maintained within these STs.
- Published
- 2020
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