Efflux pump, the masked side of beta-lactam resistance in Klebsiella pneumoniae clinical isolates.
BACKGROUND: Beta-lactamase production and porin decrease are the well-recognized mechanisms of acquired beta-lactam resistance in Klebsiella pneumoniae isolates. However, such mechanisms proved to be absent in K. pneumoniae isolates that are non susceptible to cefoxitin (FOX) and susceptible to amox...
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| Format: | Article |
| Language: | English |
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Public Library of Science (PLoS)
2009-01-01
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| Series: | PLoS ONE |
| Online Access: | http://europepmc.org/articles/PMC2652100?pdf=render |
| _version_ | 1819179613571514368 |
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| author | Jean-Marie Pages Jean-Philippe Lavigne Véronique Leflon-Guibout Estelle Marcon Frédéric Bert Latifa Noussair Marie-Hélène Nicolas-Chanoine |
| author_facet | Jean-Marie Pages Jean-Philippe Lavigne Véronique Leflon-Guibout Estelle Marcon Frédéric Bert Latifa Noussair Marie-Hélène Nicolas-Chanoine |
| author_sort | Jean-Marie Pages |
| collection | DOAJ |
| description | BACKGROUND: Beta-lactamase production and porin decrease are the well-recognized mechanisms of acquired beta-lactam resistance in Klebsiella pneumoniae isolates. However, such mechanisms proved to be absent in K. pneumoniae isolates that are non susceptible to cefoxitin (FOX) and susceptible to amoxicillin+clavulanic acid in our hospital. Assessing the role of efflux pumps in this beta-lactam phenotype was the aim of this study. METHODOLOGY/FINDINGS: MICs of 9 beta-lactams, including cloxacillin (CLX), and other antibiotic families were tested alone and with an efflux pump inhibitor (EPI), then with both CLX (subinhibitory concentrations) and EPI against 11 unique bacteremia K. pneumoniae isolates displaying the unusual phenotype, and 2 ATCC strains. CLX and EPI-dose dependent effects were studied on 4 representatives strains. CLX MICs significantly decreased when tested with EPI. A similar phenomenon was observed with piperacillin+tazobactam whereas MICs of the other beta-lactams significantly decreased only in the presence of both EPI and CLX. Thus, FOX MICs decreased 128 fold in the K. pneumoniae isolates but also 16 fold in ATCC strain. Restoration of FOX activity was CLX dose-dependent suggesting a competitive relationship between CLX and the other beta-lactams with regard to their efflux. For chloramphenicol, erythromycin and nalidixic acid whose resistance was also due to efflux, adding CLX to EPI did not increase their activity suggesting differences between the efflux process of these molecules and that of beta-lactams. CONCLUSION: This is the first study demonstrating that efflux mechanism plays a key role in the beta-lactam susceptibility of clinical isolates of K. pneumoniae. Such data clearly evidence that the involvement of efflux pumps in beta-lactam resistance is specially underestimated in clinical isolates. |
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| id | doaj.art-56c2ab3a8cb64f54aacd3f477d9ba011 |
| institution | Directory Open Access Journal |
| issn | 1932-6203 |
| language | English |
| last_indexed | 2024-12-22T22:01:14Z |
| publishDate | 2009-01-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS ONE |
| spelling | doaj.art-56c2ab3a8cb64f54aacd3f477d9ba0112022-12-21T18:11:06ZengPublic Library of Science (PLoS)PLoS ONE1932-62032009-01-0143e481710.1371/journal.pone.0004817Efflux pump, the masked side of beta-lactam resistance in Klebsiella pneumoniae clinical isolates.Jean-Marie PagesJean-Philippe LavigneVéronique Leflon-GuiboutEstelle MarconFrédéric BertLatifa NoussairMarie-Hélène Nicolas-ChanoineBACKGROUND: Beta-lactamase production and porin decrease are the well-recognized mechanisms of acquired beta-lactam resistance in Klebsiella pneumoniae isolates. However, such mechanisms proved to be absent in K. pneumoniae isolates that are non susceptible to cefoxitin (FOX) and susceptible to amoxicillin+clavulanic acid in our hospital. Assessing the role of efflux pumps in this beta-lactam phenotype was the aim of this study. METHODOLOGY/FINDINGS: MICs of 9 beta-lactams, including cloxacillin (CLX), and other antibiotic families were tested alone and with an efflux pump inhibitor (EPI), then with both CLX (subinhibitory concentrations) and EPI against 11 unique bacteremia K. pneumoniae isolates displaying the unusual phenotype, and 2 ATCC strains. CLX and EPI-dose dependent effects were studied on 4 representatives strains. CLX MICs significantly decreased when tested with EPI. A similar phenomenon was observed with piperacillin+tazobactam whereas MICs of the other beta-lactams significantly decreased only in the presence of both EPI and CLX. Thus, FOX MICs decreased 128 fold in the K. pneumoniae isolates but also 16 fold in ATCC strain. Restoration of FOX activity was CLX dose-dependent suggesting a competitive relationship between CLX and the other beta-lactams with regard to their efflux. For chloramphenicol, erythromycin and nalidixic acid whose resistance was also due to efflux, adding CLX to EPI did not increase their activity suggesting differences between the efflux process of these molecules and that of beta-lactams. CONCLUSION: This is the first study demonstrating that efflux mechanism plays a key role in the beta-lactam susceptibility of clinical isolates of K. pneumoniae. Such data clearly evidence that the involvement of efflux pumps in beta-lactam resistance is specially underestimated in clinical isolates.http://europepmc.org/articles/PMC2652100?pdf=render |
| spellingShingle | Jean-Marie Pages Jean-Philippe Lavigne Véronique Leflon-Guibout Estelle Marcon Frédéric Bert Latifa Noussair Marie-Hélène Nicolas-Chanoine Efflux pump, the masked side of beta-lactam resistance in Klebsiella pneumoniae clinical isolates. PLoS ONE |
| title | Efflux pump, the masked side of beta-lactam resistance in Klebsiella pneumoniae clinical isolates. |
| title_full | Efflux pump, the masked side of beta-lactam resistance in Klebsiella pneumoniae clinical isolates. |
| title_fullStr | Efflux pump, the masked side of beta-lactam resistance in Klebsiella pneumoniae clinical isolates. |
| title_full_unstemmed | Efflux pump, the masked side of beta-lactam resistance in Klebsiella pneumoniae clinical isolates. |
| title_short | Efflux pump, the masked side of beta-lactam resistance in Klebsiella pneumoniae clinical isolates. |
| title_sort | efflux pump the masked side of beta lactam resistance in klebsiella pneumoniae clinical isolates |
| url | http://europepmc.org/articles/PMC2652100?pdf=render |
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