期刊
INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
卷 137, 期 -, 页码 528-536出版社
ELSEVIER
DOI: 10.1016/j.ijbiomac.2019.07.001
关键词
Antibiotic hypersensitivity; Multidrug-resistant bacteria; Oxacillin; Protein aggregates; Staphylococcus aureus
资金
- National Institute of Genetic Engineering and Biotechnology
- Department of Bioprocess Engineering, Institute of Industrial and Environmental Biotechnology, National Institute of Genetic Engineering and Biotechnology, Tehran, Iran
- Department of Biomedicine, Aarhus University, Aarhus C, Denmark
Emergence of multidrug-resistant bacteria is a major global concern. According to WHO, methicillin-resistant Staphylococcus aureus (MRSA) is a threatening pathogen resistant to a wide spectrum of antibiotics. Herein, to overcome drug resistance in MRSA, we successfully integrated traditional antibacterial methods but with a novel trick that included use of hen egg-white lysozyme's special aggregates generated by fibrillization. The minimum inhibitory concentration of oxacillin (Ox) for MRSA declined from 600 mu M to <20 mu M when using aggregates. Scanning and transition electron micrographs showed completely disrupted cells when treated with aggregated protein/Ox (20 mu M). The assisting role of aggregates to induce antibiotic hypersensitivity was continuous and stable, but sub-inhibitory antibiotic concentration (20 mu M) was required again after 8 h. Investigations regarding mechanism of antibiotic hypersensitivity revealed that aggregates were oligomers but not mature fibrils. Furthermore, reactive oxygen species levels rose significantly after treating bacteria with aggregated protein/Ox. Study of resistance mechanisms indicated that in response to wall structure alterations, mecA expression dropped significantly in the presence of aggregated protein/Ox (20 mu M) relative to Ox (20 mu M). This observation can be a breakthrough in finding alternatives where antibiotic dosage can be significantly reduced, thereby preventing emergence of new multidrug-resistant bacteria. (C) 2019 Published by Elsevier B.V.
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