title: Synergistic Anti-bacterial Effects of Phellinus baumii Ethyl Acetate Extracts and β-Lactam Antimicrobial Agents Against Methicillin-Resistant Staphylococcus aureus.
abstract: BACKGROUND
  The development of new drugs or alternative therapies effective against methicillin-resistant Staphylococcus aureus (MRSA) is of great importance, and various natural anti-MRSA products are good candidates for combination therapies. We evaluated the antibacterial activities of a Phellinus baumii ethyl acetate extract (PBEAE) and its synergistic effects with β-lactams against MRSA.
  
  
  METHODS
  The broth microdilution method was used to determine the minimal inhibitory concentration (MIC) and minimal bactericidal concentration (MBC) of the PBEAE. The PBEAE synergistic effects were determined by evaluating the MICs of anti-staphylococcal antibiotic mixtures, with or without PBEAE. Anti-MRSA synergistic bactericidal effects of the PBEAE and β-lactams were assessed by time-killing assay. An ELISA was used to determine the effect of the PBEAE on penicillin binding protein (PBP)2a production.
  
  
  RESULTS
  The MICs and MBCs of PBEAE against MRSA were 256-512 and 1,024-2,048 μg/mL, respectively. The PBEAE significantly reduced MICs of all β-lactams tested, including oxacillin, cefazolin, cefepime, and penicillin. However, the PBEAE had little or no effect on the activity of non-β-lactams. Time-killing assays showed that the synergistic effects of two β-lactams (oxacillin and cefazolin) with the PBEAE were bactericidal in nature (Δlog10 colony forming unit/mL at 24 hr: 2.34-2.87 and 2.10-3.04, respectively). The PBEAE induced a dose-dependent decrease in PBP2a production by MRSA, suggesting that the inhibition of PBP2a production was a major synergistic mechanism between the β-lactams and the PBEAE.
  
  
  CONCLUSIONS
  PBEAE can enhance the efficacy of β-lactams for combined therapy in patients infected with MRSA.
authors.affiliation: Department of Clinical Laboratory Science, Chungbuk Health & Science University, Cheongju, Korea.
authors.forename: Seung Bok
authors.initials: SB
authors.lastname: Hong
authors.affiliation: Laboratory of Veterinary Physiology & Signaling, College of Veterinary Medicine and Stem Cell Research Therapeutic Institute, Kyungpook National University, Daegu, Korea.
authors.forename: Man Hee
authors.initials: MH
authors.lastname: Rhee
authors.affiliation: Division of Biotechnology and Advanced Institute of Environmental & Bioresource Sciences, College of Environmental & Bioresource Science, Chonbuk National University, Iksan, Korea.
authors.forename: Bong-Sik
authors.initials: BS
authors.lastname: Yun
authors.affiliation: Department of Pathology, Chungbuk National University College of Medicine, Cheongju, Korea.
authors.forename: Young Hoon
authors.initials: YH
authors.lastname: Lim
authors.affiliation: Department of Pathology, Chungbuk National University College of Medicine, Cheongju, Korea.
authors.forename: Hyung Geun
authors.initials: HG
authors.lastname: Song
authors.affiliation: Department of Laboratory Medicine, Chungbuk National University College of Medicine, Cheongju, Korea. ksshin@chungbuk.ac.kr.
authors.forename: Kyeong Seob
authors.initials: KS
authors.lastname: Shin
mesh_terms: D000085:Acetates / Q000737:chemistry; D000363:Agaricales / Q000737:chemistry* / Q000378:metabolism; D000890:Anti-Infective Agents / Q000737:chemistry / Q000494:pharmacology*; D004357:Drug Synergism; D004797:Enzyme-Linked Immunosorbent Assay; D055624:Methicillin-Resistant Staphylococcus aureus / Q000187:drug effects* / Q000378:metabolism; D008826:Microbial Sensitivity Tests; D046915:Penicillin-Binding Proteins / Q000032:analysis / Q000378:metabolism; D010936:Plant Extracts / Q000737:chemistry / Q000494:pharmacology*; D047090:beta-Lactams / Q000494:pharmacology*
chemical_list: D000085:Acetates; D000890:Anti-Infective Agents; D046915:Penicillin-Binding Proteins; D010936:Plant Extracts; D047090:beta-Lactams; C007650:ethyl acetate
keywords: Anti-bacterial; MRSA; Phellinus baumii; Synergy; β-lactam