title: Restoration of antibacterial activity of beta-lactams by epigallocatechin gallate against beta-lactamase-producing species depending on location of beta-lactamase.
abstract: The combined effects of (-)-epigallocatechin gallate (EGCg) and beta-lactams were investigated against various beta-lactamase-producing clinical isolates, including 21 Staphylococcus aureus, 6 Escherichia coli, 3 Klebsiella pneumoniae and 8 Serratia marcescens strains. Penicillin in combination with EGCg at 12.5 microg mL(-1) showed the most potent synergy against 100% penicillinase-producing S. aureus. However, cefotaxime or imipenem in combination with higher concentration of EGCg (100 microg mL(-1)) only showed slight synergy against 2 of 17 Gram-negative rods. Similar to the effect on the penicillinase from S. aureus, however, EGCg also directly inhibited the extracted beta-lactamases from the Gram-negative rods, thereby protecting beta-lactams from inactivation. The different effects of the combinations on different beta-lactamase-producing species were confirmed to be related to the cellular locations of beta-lactamases. In contrast to a 32.7% extracellular fraction of total beta-lactamase activity in a penicillinase-producing S. aureus, the fractions were 0.6%, 0.6% and 1.2% in a TEM-derived extended-spectrum beta-lactamase-producing E. coli, an inhibitor-resistant beta-lactamase-producing K. pneumoniae and an IMP-producing S. marcescens, respectively. In conclusion, the combination of penicillin with EGCg showed potent synergy against penicillinase-producing S. aureus in-vitro. The combinations of beta-lactams and EGCg against beta-lactamase-producing Gram-negative rods do indicate a limitation owing to the cellular location of beta-lactamases.
authors.affiliation: Department of Microbiology and Immunology, Showa University School of Medicine, 1-5-8 Hatanodai, Shinagawa-ku, Tokyo 142-8555, Japan. whzhao@med.showa-u.ac.jp
authors.forename: W-H
authors.initials: WH
authors.lastname: Zhao
authors.forename: N
authors.initials: N
authors.lastname: Asano
authors.forename: Z-Q
authors.initials: ZQ
authors.lastname: Hu
authors.forename: T
authors.initials: T
authors.lastname: Shimamura
mesh_terms: D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D002392:Catechin / Q000031:analogs & derivatives* / Q000302:isolation & purification / Q000494:pharmacology*; D004357:Drug Synergism; D006090:Gram-Negative Bacteria / Q000187:drug effects* / Q000378:metabolism; D008826:Microbial Sensitivity Tests; D001618:beta-Lactamases / Q000096:biosynthesis / Q000187:drug effects / Q000235:genetics; D047090:beta-Lactams
chemical_list: D000900:Anti-Bacterial Agents; D047090:beta-Lactams; D002392:Catechin; C045651:epigallocatechin gallate; D001618:beta-Lactamases