Peptides as adjuvants for ampicillin and oxacillin against methicillin-resistant Staphylococcus aureus (MRSA). (November 2018)

• Record Type: Journal Article
• Authors: Rishi, Praveen; Vij, Shania; Maurya, Indresh Kumar; Kaur, Ujjwal Jit; Bharati, Sanjay; Tewari, Rupinder
• Is Part Of: Microbial pathogenesis. Volume 124(2018)
• Page Start: 11
• Page End: 20
• Publication Date: 2018-11
• Subjects: Ampicillin -- Oxacillin -- Peptide-antibiotic combination -- Peptide-bacteria interaction -- Methicillin resistant Staphylococcus aureus; Pathogenic microorganisms -- Periodicals; Pathology, Molecular -- Periodicals; Communicable Diseases -- microbiology -- Periodicals; Communicable Diseases -- parasitology -- Periodicals; Micro-organismes pathogènes -- Périodiques; Pathologie moléculaire -- Périodiques; Electronic journals; 616.9041
• DOI: 10.1016/j.micpath.2018.08.023
• Languages: English
• ISSNs: 0882-4010

Abstract

Abstract: Fast emerging antibiotic resistance in pathogens requires special attention for strengthening the reservoir of antimicrobial compounds. In view of this, several peptides with known antimicrobial activities have been reported to enhance the efficacy of antibiotics against multidrug resistant (MDR) pathogens. In the present study, potential of peptides having distinct mechanism of action, if any, was evaluated to improve the efficacy of conventional antibiotics against methicillin-resistant S. aureus (MRSA). After primary screening of six peptides, two peptides namely T3 and T4 showing very high minimum inhibitory concentrations (MICs) were selected to assess their role in altering the MICs of antibiotics to which the pathogen was resistant. In the presence of the peptides, the MICs of the antibiotics were found to be reduced as per the fractional inhibitory concentration indices (FICI) and time kill assay. These observations prompted us to look for their mechanism of action. The effect of peptides on the morphology of pathogen by field emission scanning electron microscopy (FE-SEM) revealed no damage to the cells at the sub-inhibitory concentrations of the peptide which correlated well with the higher MIC of the peptide, indicating no direct impact on the pathogen. However, dielectric spectroscopy, confocal microscopy and flow cytometry confirmed the interaction and localization of peptides with the bacterial membrane. The peptides were also found to inhibit efflux of ethidium bromide which is the substrate for many proteins involved in efflux system. Therefore, it is speculated that the peptides after interacting with the membrane of the pathogen might have resulted in the inhibition of the efflux of antibiotics thereby reducing their effective concentrations. The study thus suggests that peptides with no antimicrobial activity of their own, can also enhance the efficacy of the antibiotics by interacting with the pathogen thereby, acting as adjuvants for the antibiotics. Highlights: Two peptides (T3 and T4) with no antimicrobial activity can act as adjuvants for the conventional antibiotics. Possible mechanism of action of these peptides may be inhibition of antibiotic efflux. Combination therapy is helpful to combat the multidrug resistance in Staphylococcus aureus.