Investigation of the role of Cremophor RH 40 and Cremophor EL in the inhibition of efflux pump of Pseudomonas aeruginosa
Muhammad Asim,
Yasin Ahmad,
Momin Khan,
Zeeshan Ahmad,
Awais Khalid,
Pervaiz Ahmad,
Abdulhameed Khan,
Fakhrul Ahsan,
Mohsin Kazi,
Samer H. Zyoud
Affiliations
Muhammad Asim
Institute of Basic Medical Sciences, Khyber Medical University, Peshawar, Pakistan
Yasin Ahmad
Sarhad Institute of Allied Health Sciences, Sarhad University of Science and Information Technology, Peshawar, Pakistan
Momin Khan
Corresponding author.; Institute of Basic Medical Sciences, Khyber Medical University, Peshawar, Pakistan; Sarhad Institute of Allied Health Sciences, Sarhad University of Science and Information Technology, Peshawar, Pakistan; Institute of Pathology and Diagnostic Medicine, Khyber Medical University, Peshawar, Pakistan; Department of Microbiology, Hazara University Mansehra, Khyber Pakhtunkhwa, 21300, Pakistan; Department of Physics, Hazara University Mansehra, Khyber Pakhtunkhwa, 21300, Pakistan; Department of Physics, University of Azad Jammu and Kashmir, Muzaffarabad, 13100, Pakistan; Department of Biotechnology, University of AJK, Muzaffarabad, Pakistan; Department of Pharmaceutical and Biomedical Sciences, California Northstate University College of Pharmacy, Elk Grove, CA, 95757, USA; Department of Pharmaceutics, College of Pharmacy, POBOX- 2457, King Saud University, Riyadh, 11451, Kingdom of Saudi Arabia; Department of Mathematics and Sciences, Ajman University, P.O. Box 346, Ajman, United Arab Emirates
Zeeshan Ahmad
Department of Microbiology, Hazara University Mansehra, Khyber Pakhtunkhwa, 21300, Pakistan
Awais Khalid
Department of Physics, Hazara University Mansehra, Khyber Pakhtunkhwa, 21300, Pakistan
Pervaiz Ahmad
Department of Physics, University of Azad Jammu and Kashmir, Muzaffarabad, 13100, Pakistan
Abdulhameed Khan
Department of Biotechnology, University of AJK, Muzaffarabad, Pakistan
Fakhrul Ahsan
Department of Pharmaceutical and Biomedical Sciences, California Northstate University College of Pharmacy, Elk Grove, CA, 95757, USA
Mohsin Kazi
Department of Pharmaceutics, College of Pharmacy, POBOX- 2457, King Saud University, Riyadh, 11451, Kingdom of Saudi Arabia
Samer H. Zyoud
Department of Mathematics and Sciences, Ajman University, P.O. Box 346, Ajman, United Arab Emirates; Corresponding author.
Background: There is increasing emphasis on restoring the efficacy of existing antibiotics instead of developing new ones. Objectives: This study aimed to determine the role of Cremophor EL and Cremophor RH40 in the inhibition of efflux pumps in MDR Pseudomonas aeruginosa strains. Methods: Efflux pump-active MDR strains of P. aeruginosa were identified and confirmed by flow cytometry. The identified efflux-active strains were further subjected to determination of the MIC of ciprofloxacin and the synergistic role of non-ionic surfactants (Cremophor EL and Cremophor RH40) along with ciprofloxacin. Results: Out of 30 samples, 6 strains displayed high efflux pump activity. Both Cremophor EL and Cremophor RH40 showed efflux pump inhibitory roles. A 4-fold reduction in the MIC values of ciprofloxacin was observed when Cremophor EL was used along with ciprofloxacin, while a 6-fold reduction was observed when Cremophor RH40 was used along with ciprofloxacin. Both compounds showed synergistic effects with ciprofloxacin, ticarcillin and meropenem when used in a 24-well plate efflux pump inhibitory assay. Conclusion: The inhibition of the efflux pump of MDR Pseudomonas aeruginosa by non-ionic surfactants, namely, Cremophor RH40 and Cremophor EL, provided the best strategy to restore the efficacy of ciprofloxacin.