title: Remarkable synergies between baicalein and tetracycline, and baicalein and beta-lactams against methicillin-resistant Staphylococcus aureus.
abstract: During the screening of compounds that potentiate the effect of antimicrobial agents against methicillin-resistant Staphylococcus aureus(MRSA), we found that an extract of thyme (Thymus vulgaris L) leaves greatly reduced the minimum inhibitory concentration (MIC) of tetracycline against MRSA. We isolated the effective compound and identified it as baicalein (5, 6, 7-trihydroxyflavone). One of the clinically isolated MRSA strains possessed tetK, a gene encoding active efflux pump for tetracycline. We examined the effect of baicalein on the efflux of tetracycline, using Escherichia coli KAM32/pTZ1252 carrying the tetK. The E. coli KAM32/pTZ1252 showed 8 to 16 times higher MIC than E. coli KAM32. We observed strong inhibition of transport of tetracycline by baicalein with membrane vesicles prepared from E. coli KAM32/pTZ1252. Baicalein also showed synergy with tetracycline in a MRSA strain that doesn't possess tetK, or with beta-lactams. Thus, mechanisms of the synergies seem to be versatile.
authors.affiliation: Department of Microbiology, Faculty of Pharmaceutical Sciences, Okayama University, Okayama, Japan.
authors.forename: Mai
authors.initials: M
authors.lastname: Fujita
authors.forename: Sumiko
authors.initials: S
authors.lastname: Shiota
authors.forename: Teruo
authors.initials: T
authors.lastname: Kuroda
authors.forename: Tsutomu
authors.initials: T
authors.lastname: Hatano
authors.forename: Takashi
authors.initials: T
authors.lastname: Yoshida
authors.forename: Tohru
authors.initials: T
authors.lastname: Mizushima
authors.forename: Tomofusa
authors.initials: T
authors.lastname: Tsuchiya
mesh_terms: D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D001693:Biological Transport, Active; D004357:Drug Synergism; D004926:Escherichia coli / Q000187:drug effects / Q000235:genetics; D044950:Flavanones / Q000737:chemistry / Q000494:pharmacology*; D016106:Methicillin Resistance; D008826:Microbial Sensitivity Tests; D015394:Molecular Structure; D013211:Staphylococcus aureus / Q000187:drug effects*; D013752:Tetracycline / Q000494:pharmacology*; D013753:Tetracycline Resistance / Q000235:genetics; D047090:beta-Lactams / Q000494:pharmacology*
chemical_list: D000900:Anti-Bacterial Agents; D044950:Flavanones; D047090:beta-Lactams; C006680:baicalein; D013752:Tetracycline