Article
N-acetylcysteine selectively antagonizes the activity of imipenem in Pseudomonas aeruginosa by an OprD-mediated mechanism
Author/s | Rodríguez Beltrán, Jerónimo
Cabot, Gabriel Ynés Valencia, Estela Costas, Coloma Bou, Germán Oliver, Antonio Blázquez, Jesús |
Department | Universidad de Sevilla. Departamento de Microbiología |
Publication Date | 2015-01-01 |
Deposit Date | 2017-09-28 |
Published in |
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Abstract | The modulating effect of N-acetylcysteine (NAC) on the activity of different antibiotics has been studied in Pseudomonas aeruginosa. Our results demonstrate that, in contrast to previous reports, only the activity of ... The modulating effect of N-acetylcysteine (NAC) on the activity of different antibiotics has been studied in Pseudomonas aeruginosa. Our results demonstrate that, in contrast to previous reports, only the activity of imipenem is clearly affected by NAC. MIC and checkerboard determinations indicate that the NAC-based modulation of imipenem activity is dependent mainly on OprD. SDS-PAGE of outer membrane proteins (OMPs) after NAC treatments demonstrates that NAC does not modify the expression of OprD, suggesting that NAC competitively inhibits the uptake of imipenem through OprD. Similar effects on imipenem activity were obtained with P. aeruginosa clinical isolates. Our results indicate that imipenem-susceptible P. aeruginosa strains become resistant upon simultaneous treatment with NAC and imipenem. Moreover, the generality of the observed effects of NAC on antibiotic activity was assessed with two additional bacterial species, Escherichia coli and Acinetobacter baumannii. Caution should be taken during treatments, as the activity of imipenem may be modified by physiologically attainable concentrations of NAC, particularly during intravenous and nebulized regimes. |
Funding agencies | Ministerio de Ciencia e Innovación (MICIN). España |
Project ID. | REIPI RD12/0015
FIS PI13/00063 |
Citation | Rodríguez Beltrán, J., Cabot, G., Ynés Valencia, E., Costas, C., Bou, G., Oliver, A. y Blázquez, J. (2015). N-acetylcysteine selectively antagonizes the activity of imipenem in Pseudomonas aeruginosa by an OprD-mediated mechanism. Antimicrobial Agents and Chemotherapy, 59 (6), 3246-3251. |
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