title: Sertraline enhances the activity of antimicrobial agents against pathogens of clinical relevance.
abstract: BACKGROUND
  Serotonin reuptake inhibitors were recently reported to possess antimicrobial potentials, potentiate activity of several antibiotics, reverse multidrug resistant phenotypes of bacteria and make them susceptible to previously resistant drugs. We investigated antimicrobial potentials of sertraline (SR) against ATCC strains, clinical isolates of Staphylococcus aureus, Escherichia coli and Pseudomonas aeruginosa alone and in-combination with seven antibiotics. Antifungal activity was investigated against four fungal strains including Aspergillus niger, Aspergillus fumigatus, Aspergillus flavus, and Fusarium solani. Intrinsic antibacterial action and Minimum Inhibitory Concentrations (MICs) were determined using well assay, nutrient broth and agar dilution techniques. Disk diffusion and nutrient broth methods were used to study bacterial susceptibility to SR. Minimum Fungicidal Concentrations (MFCs) of SR were determined using Sabouraud dextrose Agar (SDA).
  
  
  RESULTS
  Sertraline possesses strong intrinsic antibacterial, antifungal activities and has augmented the antibacterial activities of antibiotics. For S. aureus ATCC 6538, E. coli ATCC 8739 and P. aeruginosa ATCC 9027, the MICs of SR were 20, 40 and 60 μg ml(-1), respectively, whereas 55.5% clinical isolates of S. aureus and 50% of E. coli strains were inhibited at 20 and 60 μg ml(-1) of SR, respectively. Among the tested fungi, 60% of A. niger and A. fumigatus were inhibited at 40 and 80 μg ml(-1), respectively. MFCs were 60 and 80 μg ml(-1) for A. flavus and F. solani, respectively. Antibacterial activities of all antibiotics were significantly increased (p < 0.001) with the addition of SR 100 μg ml(-1) against all tested bacteria.
  
  
  CONCLUSIONS
  Combination study revealed that SR had significantly increased the activity of antibiotics, and some previously resistant strains were made susceptible. Thus antidepressants are potential sources of resistance modifying agents when used in combination.
authors.affiliation: Department of Pharmacy, University of Malakand, Khyber Pakhtoonkhwa, 18000 Pakistan.
authors.forename: Muhammad
authors.initials: M
authors.lastname: Ayaz
authors.affiliation: Department of Pharmacy, University of Peshawar, Peshawar, Pakistan.
authors.forename: Fazal
authors.initials: F
authors.lastname: Subhan
authors.affiliation: Institute of Basic Medical Sciences (IBMS), Khyber Medical University, Peshawar, Pakistan.
authors.forename: Jawad
authors.initials: J
authors.lastname: Ahmed
authors.affiliation: Department of Pharmacology, Riphah Institute of Pharmaceutical Sciences, Riphah International University, Islamabad, Pakistan.
authors.forename: Arif-Ullah
authors.initials: AU
authors.lastname: Khan
authors.affiliation: Department of Pharmacy, University of Malakand, Khyber Pakhtoonkhwa, 18000 Pakistan.
authors.forename: Farhat
authors.initials: F
authors.lastname: Ullah
authors.affiliation: Department of Pharmacy, University of Swabi, Swabi, Pakistan.
authors.forename: Ihsan
authors.initials: I
authors.lastname: Ullah
authors.affiliation: Department of Pharmacy, University of Peshawar, Peshawar, Pakistan.
authors.forename: Gowhar
authors.initials: G
authors.lastname: Ali
authors.affiliation: University College of Pharmacy, University of The Punjab Lahore, Lahore, 54000 Pakistan.
authors.forename: Nawazish-I-Husain
authors.initials: NI
authors.lastname: Syed
authors.affiliation: Department of Pharmacy, Kohat University of Science and Technology, Kohat, Pakistan.
authors.forename: Sajid
authors.initials: S
authors.lastname: Hussain
keywords: ATCC; Minimum fungicidal concentration; Sertraline; Well assay