Quorum quenching as a strategy for treating Methicillin Resistant S. aureus (MRSA) - Effect of ε-Polylysine, ethanolic extracts of guava leaves and mango seed kernel

Abstract

Staphylococcus aureus accessory gene regulatory Quorum Sensing (QS) system facilitates biofilm formation and biofilms are major contributors for antimicrobial resistance. Quorum quenchers could be used as an adjunct to antibiotics to reduce the development of drug resistance. The objective of this study was to evaluate the sub-inhibitory concentration of ethanolic extracts of Mango Seed Kernel Extract (MSKE), Guava Leaf Extract (GLE) and ε-Polylysine (ε-PL) against quorum sensing mediated virulence factors of S. aureus. We evaluated the antibacterial and Quorum Quenching (QQ) activity of these compounds on 10 MRSA and 10 MSSA isolates. The antibacterial activity was tested by disc diffusion assay. The Minimum Inhibitory Concentrations (MIC) for MRSA isolates were: 20 µg/mL for ε-Polylysine, 20 µg/mL for MSKE extract and GLE and for MSSA isolates were:12.5 µg/mL for ε-Polylysine, 20 µg/mL for MSKE extract and GLE. Quorum Sensing Inhibition (QSI) activity was determined at sub-MIC of 10 µg/mL of all the compounds by studying inhibition of the delta hemolysin on sheep blood agar plate and motility on soft agar media. All these compounds affected the motility and expression of δ-hemolysin activity which confirms that these compounds interfere with the QS activity. The QQ effect was confirmed by quantitation of hld (delta hemolysin) transcript and rnaIII transcript by qPCR. The results of this study will be presented as proof of QQ activity by ε-PL, MSKE, and GLE on S. aureus in general and MRSA in particular, as an attractive proposition for adjunct therapy and anti-virulence therapy of MRSA infections.