title: Antibacterial Activity and Antibiotic-Enhancing Effects of Honeybee Venom against Methicillin-Resistant Staphylococcus aureus.
abstract: Methicillin-resistant Staphylococcus aureus (MRSA), along with other antibiotic resistant bacteria, has become a significant social and clinical problem. There is thus an urgent need to develop naturally bioactive compounds as alternatives to the few antibiotics that remain effective. Here we assessed the in vitro activities of bee venom (BV), alone or in combination with ampicillin, penicillin, gentamicin or vancomycin, on growth of MRSA strains. The antimicrobial activity of BV against MRSA strains was investigated using minimum inhibitory concentrations (MIC), minimum bactericidal concentrations (MBC) and a time-kill assay. Expression of atl which encodes murein hydrolase, a peptidoglycan-degrading enzyme involved in cell separation, was measured by reverse transcription-polymerase chain reaction. The MICs of BV were 0.085 µg/mL and 0.11 µg/mL against MRSA CCARM 3366 and MRSA CCARM 3708, respectively. The MBC of BV against MRSA 3366 was 0.106 µg/mL and that against MRSA 3708 was 0.14 µg/mL. The bactericidal activity of BV corresponded to a decrease of at least 3 log CFU/g cells. The combination of BV with ampicillin or penicillin yielded an inhibitory concentration index ranging from 0.631 to 1.002, indicating a partial and indifferent synergistic effect. Compared to ampicillin or penicillin, both MRSA strains were more susceptible to the combination of BV with gentamicin or vancomycin. The expression of atl gene was increased in MRSA 3366 treated with BV. These results suggest that BV exhibited antibacterial activity and antibiotic-enhancing effects against MRSA strains. The atl gene was increased in MRSA exposed to BV, suggesting that cell division was interrupted. BV warrants further investigation as a natural antimicrobial agent and synergist of antibiotic activity.
authors.affiliation: Rural Development Administration, National Academy of Agricultural Science, Wanju, Chonbuk 55365, Korea. sangmih@korea.kr.
authors.forename: Sang Mi
authors.initials: SM
authors.lastname: Han
authors.affiliation: Rural Development Administration, National Academy of Agricultural Science, Wanju, Chonbuk 55365, Korea. jmyellow80@naver.com.
authors.forename: Joung Min
authors.initials: JM
authors.lastname: Kim
authors.affiliation: Rural Development Administration, National Academy of Agricultural Science, Wanju, Chonbuk 55365, Korea. iphong20@korea.kr.
authors.forename: In Pyo
authors.initials: IP
authors.lastname: Hong
authors.affiliation: Rural Development Administration, National Academy of Agricultural Science, Wanju, Chonbuk 55365, Korea. wooso1@korea.kr.
authors.forename: Soon Ok
authors.initials: SO
authors.lastname: Woo
authors.affiliation: Rural Development Administration, National Academy of Agricultural Science, Wanju, Chonbuk 55365, Korea. kimsegun@korea.kr.
authors.forename: Se Gun
authors.initials: SG
authors.lastname: Kim
authors.affiliation: Rural Development Administration, National Academy of Agricultural Science, Wanju, Chonbuk 55365, Korea. tddas@naver.com.
authors.forename: He Rye
authors.initials: HR
authors.lastname: Jang
authors.affiliation: School of Biomedical Sciences, Charles Sturt University, Bathurst 2795, Australia. spak@csu.edu.au.
authors.forename: Sok Cheon
authors.initials: SC
authors.lastname: Pak
mesh_terms: D000667:Ampicillin / Q000494:pharmacology; D000818:Animals; D000900:Anti-Bacterial Agents / Q000302:isolation & purification / Q000494:pharmacology*; D001426:Bacterial Proteins / Q000819:agonists / Q000235:genetics / Q000378:metabolism; D001514:Bee Venoms / Q000302:isolation & purification / Q000494:pharmacology*; D001516:Bees / Q000737:chemistry / Q000502:physiology; D015169:Colony Count, Microbial; D004357:Drug Synergism; D015870:Gene Expression; D005839:Gentamicins / Q000494:pharmacology*; D055624:Methicillin-Resistant Staphylococcus aureus / Q000187:drug effects* / Q000201:enzymology / Q000235:genetics / Q000254:growth & development; D008826:Microbial Sensitivity Tests; D009238:N-Acetylmuramoyl-L-alanine Amidase / Q000235:genetics / Q000378:metabolism; D010406:Penicillins / Q000494:pharmacology; D014640:Vancomycin / Q000494:pharmacology*
chemical_list: D000900:Anti-Bacterial Agents; D001426:Bacterial Proteins; D001514:Bee Venoms; D005839:Gentamicins; D010406:Penicillins; D014640:Vancomycin; D000667:Ampicillin; D009238:N-Acetylmuramoyl-L-alanine Amidase
keywords: MRSA; antibacterial effect; antibiotic effects; atl; bee venom