Curcumin reverse methicillin resistance in Staphylococcus aureus.
Curcumin, a natural polyphenolic flavonoid extracted from the rhizome of Curcuma longa L., was shown to possess superior potency to resensitize methicillin-resistant Staphylococcus aureus (MRSA) to antibiotics. Previous studies have shown the synergistic activity of curcumin with β-lactam and quinolone antibiotics. Further, to understand the anti-MRSA mechanism of curcumin, we investigated the potentiated effect of curcumin by its interaction in diverse conditions. The mechanism of anti-MRSA action of curcumin was analyzed by the viability assay in the presence of detergents, ATPase inhibitors and peptidoglycan (PGN) from S. aureus, and the PBP2a protein level was analyzed by western blotting. The morphological changes in the curcumin-treated MRSA strains were investigated by transmission electron microscopy (TEM). We analyzed increased susceptibility to MRSA isolates in the presence of curcumin. The optical densities at 600 nm (OD600) of the suspensions treated with the combinations of curcumin with triton X-100 and Tris were reduced to 63% and 59%, respectively, compared to curcumin without treatment. N,N'-dicyclohexylcarbodiimide (DCCD) and sodium azide (NaN3) were reduced to 94% and 55%, respectively. When peptidoglycan (PGN) from S. aureus was combined with curcumin, PGN (0-125 μg/mL) gradually blocked the antibacterial activity of curcumin (125 μg/mL); however, at a concentration of 125 µg/mL PGN, it did not completely block curcumin. Curcumin has a significant effect on the protein level of PBP2a. The TEM images of MRSA showed damage of the cell wall, disruption of the cytoplasmic contents, broken cell membrane and cell lysis after the treatment of curcumin. These data indicate a remarkable antibacterial effect of curcumin, with membrane permeability enhancers and ATPase inhibitors, and curcumin did not directly bind to PGN on the cell wall. Further, the antimicrobial action of curcumin involved in the PBP2a-mediated resistance mechanism was investigated.
BK21 Plus Team, Professional Graduate School of Oriental Medicine, Wonkwang University, Iksan, Jeonbuk 570-749, Korea.
Su-Hyun
SH
Mun
BK21 Plus Team, Professional Graduate School of Oriental Medicine, Wonkwang University, Iksan, Jeonbuk 570-749, Korea.
Sung-Bae
SB
Kim
BK21 Plus Team, Professional Graduate School of Oriental Medicine, Wonkwang University, Iksan, Jeonbuk 570-749, Korea.
Ryong
R
Kong
Department of Oriental Pharmacy, College of Pharmacy, Wonkwang Oriental Medicines Research Institute, Institute of Biotechnology, Wonkwang University, Iksan, Jeonbuk 570-749, Korea.
Jang-Gi
JG
Choi
Standardized Material Bank for New Botanical Drugs, College of Pharmacy, Wonkwang University, Iksan, Jeonbuk 570-749, Korea.
Youn-Chul
YC
Kim
Department of Oriental Medicine Resources, College of Bio Industry Science, Sunchon National University, Sunchon, Jeonnam 540-742, Korea.
Dong-Won
DW
Shin
Department of Oriental Pharmacy, College of Pharmacy, Wonkwang Oriental Medicines Research Institute, Institute of Biotechnology, Wonkwang University, Iksan, Jeonbuk 570-749, Korea.
Ok-Hwa
OH
Kang
BK21 Plus Team, Professional Graduate School of Oriental Medicine, Wonkwang University, Iksan, Jeonbuk 570-749, Korea. sssimi@wku.ac.kr.
Dong-Yeul
DY
Kwon
D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology*; D003474:Curcumin / Q000494:pharmacology*; D016106:Methicillin Resistance / Q000187:drug effects*; D055624:Methicillin-Resistant Staphylococcus aureus / Q000378:metabolism*; D050296:Microbial Viability / Q000187:drug effects*
D000894:Anti-Inflammatory Agents, Non-Steroidal; D003474:Curcumin