Potentiating activity of luteolin on membrane permeabilizing agent and ATPase inhibitor against methicillin-resistant Staphylococcus aureus

Dae-Ki Joung; Young-Seob Lee; Sin-Hee Han; Sang-Won Lee; Seon-Woo Cha; Su-Hyun Mun; Ryong Kong; Ok-Hwa Kang; Ho-Jun Song; Dong-Won Shin; Dong-Yeul Kwon

doi:10.1016/j.apjtm.2015.12.004

Potentiating activity of luteolin on membrane permeabilizing agent and ATPase inhibitor against methicillin-resistant Staphylococcus aureus

Asian Pac J Trop Med. 2016 Jan;9(1):19-22. doi: 10.1016/j.apjtm.2015.12.004. Epub 2015 Dec 19.

Authors

Affiliations

¹ Department of Oriental Pharmacy, College of Pharmacy and Wonkwang-Oriental Medicines Research Institute, Wonkwang University, Iksan, Jeonbuk 570-749, Republic of Korea.
² Department of Herbal Crop Research, National Institute of Horticultural & Herbal Science, RDA, 92 Bisanro, Eumsung, Chungbuk 369-873, Republic of Korea.
³ BK21 Plus Team, Professional Graduate School of Oriental Medicine, Wonkwang University, Iksan, Jeonbuk 570-749, Republic of Korea.
⁴ Department of Oriental Medicine Resources, Sunchon National University, Sunchon, Jeonnam 540-742, Republic of Korea.
⁵ BK21 Plus Team, Professional Graduate School of Oriental Medicine, Wonkwang University, Iksan, Jeonbuk 570-749, Republic of Korea; Department of Oriental Pharmacy, College of Pharmacy and Wonkwang-Oriental Medicines Research Institute, Wonkwang University, Iksan, Jeonbuk 570-749, Republic of Korea. Electronic address: sssimi@wku.ac.kr.

PMID: 26851780
DOI: 10.1016/j.apjtm.2015.12.004

Abstract

Objective: To investigate the mechanism of antibacterial activity of luteolin (LUT) against methicillin-resistant Staphylococcus aureus (MRSA).

Methods: The mechanism of anti-MRSA activity of LUT was analyzed by the viability assay in membrane permeabilizing agent, ATPase inhibitors, and peptidoglycan (PGN) derived from Staphylococcus aureus (S. aureus). Also, transmission electron microscopy was used to monitor survival characteristics and changes in S. aureus morphology.

Results: Compared to the LUT alone, the optical density of suspensions treated with the combination of 125 μg/mL Tris and 250 μg/mL N,N'-dicyclohexylcarbodiimide were reduced to 60% and 46% of the control, respectively. PGN (15.6 μg/mL) gradually impeded the activity of LUT, and PGN (62.5 μg/mL) completely blocked the activity of LUT on S. aureus.

Conclusions: Increased susceptibility to LUT with the Tris-dicyclohexylcarbodiimide combinations is evident in all tested MRSA isolates. The results indicate LUT synergy in increasing cytoplasmic membrane permeability and inhibiting ATPase. S. aureus PGN directly blocks the antibacterial activity of LUT, suggesting the direct binding of LUT with PGN. These findings may be validated for the development of antibacterial agent for low MRSA resistance.

Keywords: ATPase inhibitor; Luteolin; Membrane permeabilizing agent; Methicillin-resistant Staphylococcus aureus; Peptidoglycan.