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dc.contributor.authorLiu, Xiaofen
dc.contributor.authorPai, Pei-Jin
dc.contributor.authorZhang, Weipeng
dc.contributor.authorHu, Yingwei
dc.contributor.authorDong, Xiaojing
dc.contributor.authorQian, Pei-Yuan
dc.contributor.authorChen, Daijie
dc.contributor.authorLam, Henry
dc.date.accessioned2021-07-06T11:33:58Z
dc.date.available2021-07-06T11:33:58Z
dc.date.issued2016
dc.identifier.citationLiu, X., Pai, P.-J., Zhang, W., Hu, Y., Dong, X., Qian, P., … Lam, H. (2016). Proteomic response of methicillin-resistant S. aureus to a synergistic antibacterial drug combination: a novel erythromycin derivative and oxacillin. Scientific Reports, 6(1). doi:10.1038/srep19841
dc.identifier.issn2045-2322
dc.identifier.pmid26806358
dc.identifier.doi10.1038/srep19841
dc.identifier.urihttp://hdl.handle.net/10754/670028
dc.description.abstractThe use of antibacterial drug combinations with synergistic effects is increasingly seen as a critical strategy to combat multi-drug resistant bacteria such as methicillin-resistant Staphylococcus aureus (MRSA). In this work, the proteome responses in MRSA under the stress of a sub-inhibitory dose of a synergistic drug combination of a novel erythromycin derivative, SIPI-8294, and oxacillin, were studied by label-free quantitative proteomics. Several control treatment groups were designed to isolate proteome responses potentially related to the synergy: (1) the non-synergistic drug combination of erythromycin and oxacillin, (2) SIPI-8294 only, (3) oxacillin only and (4) erythromycin only. Results showed that 200 proteins were differentially expressed in SIPI-8294/oxacillin-treated cells. Among these proteins, the level of penicillin binding protein 2a, the protein mainly responsible for oxacillin resistance in MRSA, was four times lower in the SIPI-8294/oxacillin group than in the erythromycin/oxacillin group, suggesting that SIPI-8294 may interfere with this known oxacillin resistance mechanism. Moreover, hierarchical clustering analysis of differentially expressed proteins under different treatments revealed that SIPI-8294/oxacillin elicits very different responses than the individual drugs or the non-synergistic erythromycin/oxacillin combination. Bioinformatic analysis indicated that the synergistic effect can be further traced to a disruption in oxidation-reduction homeostasis and cell wall biosynthesis.
dc.description.sponsorshipWe thank Joyce Wong for technical assistance with the LC-MS/MS, HKUST Biosciences Central Research Facility (BioCRF) for providing mass spectrometry services and Materials Characterization and Preparation Facility (MCPF) for providing scanning electron microscope. We also thank Prof. Shunyi Shen in Shanghai Institute of Pharmaceutical Industry for providing SIPI-8294 for the mechanism study. This research is supported by the Research Grant Council of the Hong Kong Special Administrative Region Government, China (Grant No. 16302614 and 16100415) and the National Natural Science Foundation of China (Grant No. 81273413 and 81573329).
dc.publisherSpringer Science and Business Media LLC
dc.relation.urlhttp://www.nature.com/articles/srep19841
dc.rightsArchived with thanks to SCIENTIFIC REPORTS
dc.rights.urihttps://creativecommons.org/licenses/by/4.0
dc.titleProteomic response of methicillin-resistant S. aureus to a synergistic antibacterial drug combination: a novel erythromycin derivative and oxacillin
dc.typeArticle
dc.contributor.departmentKAUST Global Partnership Program, Division of Life Science, Hong Kong University of Science and Technology, Kowloon, Hong Kong
dc.identifier.journalSCIENTIFIC REPORTS
dc.identifier.pmcidPMC4726183
dc.identifier.wosutWOS:000368740300001
dc.eprint.versionPost-print
dc.contributor.institutionDepartment of Chemical and Biomolecular Engineering, Hong Kong University of Science and Technology, Kowloon, Hong Kong
dc.contributor.institutionInstitute of Antibiotics, Fudan University, Shanghai, China
dc.contributor.institutionKey Laboratory of Clinical Pharmacology of Antibiotics, National Population and Family Planning Commission, Shanghai, China
dc.contributor.institutionGraduate School of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan
dc.contributor.institutionCenter for Infectious Disease and Cancer Research, Kaohsiung Medical University, Kaohsiung, Taiwan
dc.contributor.institutionState Key Laboratory of New Drug and Pharmaceutical Process, Shanghai Institute of Pharmaceutical Industry, China State Institute of Pharmaceutical Industry, Shanghai, China
dc.contributor.institutionSchool of Pharmacy, Shanghai Jiao Tong University, Shanghai, China
dc.contributor.institutionDivision of Biomedical Engineering, Hong Kong University of Science and Technology, Kowloon, Hong Kong
dc.identifier.volume6
dc.identifier.issue1
kaust.personZhang, Weipeng
kaust.personQian, Pei-yuan
dc.identifier.eid2-s2.0-84955494217


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