title: N-acetylcysteine selectively antagonizes the activity of imipenem in Pseudomonas aeruginosa by an OprD-mediated mechanism.
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 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.
authors: Instituto de Biomedicina de Sevilla, Consejo Superior de Investigaciones Científicas and Universidad de Sevilla, Seville, Spain Centro Nacional de Biotecnología, Madrid, Spain.
authors: Jerónimo
authors: J
authors: Rodríguez-Beltrán
authors: Instituto de Biomedicina de Sevilla, Consejo Superior de Investigaciones Científicas and Universidad de Sevilla, Seville, Spain Centro Nacional de Biotecnología, Madrid, Spain Servicio de Microbiología and Unidad de Investigación, Hospital Universitario Son Espases, Instituto de Investigación Sanitaria de Palma, Palma de Mallorca, Spain Complejo Hospitalario Universitario A Coruña, A Coruña, Spain.
authors: Gabriel
authors: G
authors: Cabot
authors: Instituto de Biomedicina de Sevilla, Consejo Superior de Investigaciones Científicas and Universidad de Sevilla, Seville, Spain Centro Nacional de Biotecnología, Madrid, Spain.
authors: Estela Ynés
authors: EY
authors: Valencia
authors: Instituto de Biomedicina de Sevilla, Consejo Superior de Investigaciones Científicas and Universidad de Sevilla, Seville, Spain Centro Nacional de Biotecnología, Madrid, Spain.
authors: Coloma
authors: C
authors: Costas
authors: Complejo Hospitalario Universitario A Coruña, A Coruña, Spain.
authors: German
authors: G
authors: Bou
authors: Servicio de Microbiología and Unidad de Investigación, Hospital Universitario Son Espases, Instituto de Investigación Sanitaria de Palma, Palma de Mallorca, Spain.
authors: Antonio
authors: A
authors: Oliver
authors: Instituto de Biomedicina de Sevilla, Consejo Superior de Investigaciones Científicas and Universidad de Sevilla, Seville, Spain Centro Nacional de Biotecnología, Madrid, Spain jblazquez-ibis@us.es.
authors: Jesús
authors: J
authors: Blázquez
mesh_terms: D000111:Acetylcysteine / Q000494:pharmacology*; D040981:Acinetobacter baumannii / Q000187:drug effects; D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D004926:Escherichia coli / Q000187:drug effects; D015964:Gene Expression Regulation, Bacterial / Q000187:drug effects; D015378:Imipenem / Q000494:pharmacology*; D008826:Microbial Sensitivity Tests; D018272:Porins / Q000378:metabolism*; D011550:Pseudomonas aeruginosa / Q000187:drug effects* / Q000378:metabolism*
chemical_list: D000900:Anti-Bacterial Agents; D018272:Porins; C077157:OprD protein, Pseudomonas aeruginosa; D015378:Imipenem; D000111:Acetylcysteine