Improving the antimicrobial efficacy against resistant Staphylococcus aureus by a combined use of conjugated oligoelectrolytes


Autoři: Elias L. Bazan aff001;  Lin Ruan aff001;  Cheng Zhou aff001
Působiště autorů: School of Chemical and Biomedical Engineering, Nanyang Technological University, Singapore aff001;  Singapore Centre on Environmental Life Sciences Engineering (SCELSE), Nanyang Technological University, Singapore aff002
Vyšlo v časopise: PLoS ONE 14(11)
Kategorie: Research Article
doi: 10.1371/journal.pone.0224816

Souhrn

Two membrane-intercalating conjugated oligoelectrolytes (COEs), namely COE-D8 and COE-S6, were combined to achieve enhanced antimicrobial efficacy. COE-D8 has a shorter molecular length than COE-S6 and is typical of effective antimicrobial COE molecules, presumably due to its prominent membrane disrupting function. In contrast, COE-D6 exhibits lower efficacy against bacteria and lower toxicity toward mammalian cells. Surprisingly, after supplementing 8 μM COE-S6, the minimum inhibitory concentration (MIC) of COE-D8 against methicillin-resistant Staphylococcus aureus (MRSA) was improved 8-fold, from 0.5 μM to 0.063 μM (0.050 μg mL−1). No increased toxicity toward mammalian cells was observed by the combination of COEs, as indicated by cytotoxicity measurements using the 3T3 cell line. Indeed, there is an extended ratio between the half maximal inhibitory concentration based on 3T3 cells to MIC against MRSA from 12 to greater than 256. Biophysical experiments using liposome models suggest that COE-S6 promotes the interactions between COE-D8 and lipid bilayers, which is in agreement with damages of cellular permeability and morphology, as observed by confocal microscopy and scanning electron microscopy. The application of a combined mixture of COEs further demonstrates their promising potential as a new class of antimicrobial agents with high efficacy and selectivity.

Klíčová slova:

Antimicrobials – Cytotoxicity – Lipid bilayer – Methicillin-resistant Staphylococcus aureus – Scanning electron microscopy – Staphylococcus aureus – Vancomycin – NIH 3T3 cells


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