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Modification of the Susceptibility of Gram-Negative Rods Producing ESβLS to β-Lactams by the Efflux Phenomenon
The production of β-lactamases is the most important mechanism of Gram-negative rod resistance to β-lactams. Resistance to ceftazidime and cefepime in clinical isolates of Enterobacteriaceae (especially ESβL-positive E. coli and K. pneumoniae) and P. aeruginosa is life-threatening. However, all stra...
Autores principales: | , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Public Library of Science
2015
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4368753/ https://www.ncbi.nlm.nih.gov/pubmed/25793625 http://dx.doi.org/10.1371/journal.pone.0119997 |
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author | Laudy, Agnieszka E. Osińska, Paula Namysłowska, Alicja Zając, Olga Tyski, Stefan |
author_facet | Laudy, Agnieszka E. Osińska, Paula Namysłowska, Alicja Zając, Olga Tyski, Stefan |
author_sort | Laudy, Agnieszka E. |
collection | PubMed |
description | The production of β-lactamases is the most important mechanism of Gram-negative rod resistance to β-lactams. Resistance to ceftazidime and cefepime in clinical isolates of Enterobacteriaceae (especially ESβL-positive E. coli and K. pneumoniae) and P. aeruginosa is life-threatening. However, all strains of the above mentioned species possess chromosomally encoded RND efflux pump systems in addition to β-lactamase production. The main goal of this study was to assess the role of efflux pump systems in cefepime and/or ceftazidime resistant phenotypes of ESβL-positive clinical strains of Enterobacteriaceae and P. aeruginosa. The influence of the efflux pump inhibitor PAβN on the minimum inhibitory concentration (MIC) values of tested cephalosporins was species-dependent. Generally, a significant reduction (at least four-fold) of β-lactam MICs was observed in the presence of PAβN only in the case of P. aeruginosa clinical isolates as well as the ESβL-producing transformant PAO1161 ΔampC. The usage of this agent resulted in the restoration of susceptibility to cefepime and/or ceftazidime in the majority of the P. aeruginosa ESβL-positive strains with low and moderate resistance to the above cephalosporins. Moreover, an outer membrane permeabilizing effect in the presence of PAβN was identified. Strain-dependent β-lactamase leakage upon PAβN or β-lactam treatment was demonstrated. The most important observation was the restoration of susceptibility of P. aeruginosa WUM226 to cefepime (MIC decrease from 32 to 4 mg/L) and ceftazidime (MIC decrease from 128 to 4 mg/L) in the presence of PAβN, which occurred despite an almost complete lack of β-lactamase leakage from bacterial cells. In conclusion, these data indicate that RND efflux pumps can modify the susceptibility to β-lactams in Gram-negative rods producing ESβLs. However, this phenomenon occurs only in P. aeruginosa strains and was not observed among E. coli and K. pneumoniae strains, representing the Enterobacteriaceae family. |
format | Online Article Text |
id | pubmed-4368753 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2015 |
publisher | Public Library of Science |
record_format | MEDLINE/PubMed |
spelling | pubmed-43687532015-03-27 Modification of the Susceptibility of Gram-Negative Rods Producing ESβLS to β-Lactams by the Efflux Phenomenon Laudy, Agnieszka E. Osińska, Paula Namysłowska, Alicja Zając, Olga Tyski, Stefan PLoS One Research Article The production of β-lactamases is the most important mechanism of Gram-negative rod resistance to β-lactams. Resistance to ceftazidime and cefepime in clinical isolates of Enterobacteriaceae (especially ESβL-positive E. coli and K. pneumoniae) and P. aeruginosa is life-threatening. However, all strains of the above mentioned species possess chromosomally encoded RND efflux pump systems in addition to β-lactamase production. The main goal of this study was to assess the role of efflux pump systems in cefepime and/or ceftazidime resistant phenotypes of ESβL-positive clinical strains of Enterobacteriaceae and P. aeruginosa. The influence of the efflux pump inhibitor PAβN on the minimum inhibitory concentration (MIC) values of tested cephalosporins was species-dependent. Generally, a significant reduction (at least four-fold) of β-lactam MICs was observed in the presence of PAβN only in the case of P. aeruginosa clinical isolates as well as the ESβL-producing transformant PAO1161 ΔampC. The usage of this agent resulted in the restoration of susceptibility to cefepime and/or ceftazidime in the majority of the P. aeruginosa ESβL-positive strains with low and moderate resistance to the above cephalosporins. Moreover, an outer membrane permeabilizing effect in the presence of PAβN was identified. Strain-dependent β-lactamase leakage upon PAβN or β-lactam treatment was demonstrated. The most important observation was the restoration of susceptibility of P. aeruginosa WUM226 to cefepime (MIC decrease from 32 to 4 mg/L) and ceftazidime (MIC decrease from 128 to 4 mg/L) in the presence of PAβN, which occurred despite an almost complete lack of β-lactamase leakage from bacterial cells. In conclusion, these data indicate that RND efflux pumps can modify the susceptibility to β-lactams in Gram-negative rods producing ESβLs. However, this phenomenon occurs only in P. aeruginosa strains and was not observed among E. coli and K. pneumoniae strains, representing the Enterobacteriaceae family. Public Library of Science 2015-03-20 /pmc/articles/PMC4368753/ /pubmed/25793625 http://dx.doi.org/10.1371/journal.pone.0119997 Text en © 2015 Laudy et al http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited. |
spellingShingle | Research Article Laudy, Agnieszka E. Osińska, Paula Namysłowska, Alicja Zając, Olga Tyski, Stefan Modification of the Susceptibility of Gram-Negative Rods Producing ESβLS to β-Lactams by the Efflux Phenomenon |
title | Modification of the Susceptibility of Gram-Negative Rods Producing ESβLS to β-Lactams by the Efflux Phenomenon |
title_full | Modification of the Susceptibility of Gram-Negative Rods Producing ESβLS to β-Lactams by the Efflux Phenomenon |
title_fullStr | Modification of the Susceptibility of Gram-Negative Rods Producing ESβLS to β-Lactams by the Efflux Phenomenon |
title_full_unstemmed | Modification of the Susceptibility of Gram-Negative Rods Producing ESβLS to β-Lactams by the Efflux Phenomenon |
title_short | Modification of the Susceptibility of Gram-Negative Rods Producing ESβLS to β-Lactams by the Efflux Phenomenon |
title_sort | modification of the susceptibility of gram-negative rods producing esβls to β-lactams by the efflux phenomenon |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4368753/ https://www.ncbi.nlm.nih.gov/pubmed/25793625 http://dx.doi.org/10.1371/journal.pone.0119997 |
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