Synergistic effect of tetrandrine and ethidium bromide against methicillin-resistant Staphylococcus aureus (MRSA).
Methicillin-resistant Staphylococcus aureus (MRSA) along with other resistant bacteria have become a significant social and clinical problem. Therefore, there is an urgent need to develop bioactive compounds from natural products as alternatives to the very few antibiotics that remain effective. Recently, the efflux mechanism has been identified as the main contributor to antibiotic resistance in bacteria. This study therefore aimed to evaluate tetrandrine (TET), an efflux pump inhibitor (EPI), as a potential antibiotic against MRSA. We investigated the antimicrobial activity of TET against 17 MRSA strains, of which 3 selected strains were studied in further detail using a time-kill assay. When these bacterial strains (1 × 10(6) colony-forming units (cfu)/ml) were incubated with TET in a time-kill assay, log-scale bactericidal activity was observed, which lasted for 24 hr. In addition, TET exhibits a synergistic effect when combined with the multi-drug resistance (MDR)-efflux pump substrate ethidium bromide (EtBr). Structure-function studies of the antibiotic activity of TET in combination with EtBr may lead to the discovery of more effective efflux pump inhibitors.
Young-Seob
YS
Lee
Sin-Hee
SH
Han
Su-Hwan
SH
Lee
Young-Guk
YG
Kim
Chung-Berm
CB
Park
Ok-Hwa
OH
Kang
Joon-Ho
JH
Keum
Sung-Bae
SB
Kim
Su-Hyun
SH
Mun
Dong-Won
DW
Shin
Dong-Yeul
DY
Kwon
D000900:Anti-Bacterial Agents / Q000008:administration & dosage / Q000494:pharmacology*; D001426:Bacterial Proteins / Q000235:genetics; D044182:Benzylisoquinolines / Q000008:administration & dosage / Q000494:pharmacology*; D015195:Drug Design; D004357:Drug Synergism; D004996:Ethidium / Q000008:administration & dosage / Q000494:pharmacology*; D005798:Genes, Bacterial; D055624:Methicillin-Resistant Staphylococcus aureus / Q000187:drug effects* / Q000235:genetics; D008826:Microbial Sensitivity Tests; D015394:Molecular Structure; D046915:Penicillin-Binding Proteins
D000900:Anti-Bacterial Agents; D001426:Bacterial Proteins; D044182:Benzylisoquinolines; D046915:Penicillin-Binding Proteins; C487789:mecA protein, Staphylococcus aureus; C009438:tetrandrine; D004996:Ethidium