Antibiotic hypersensitivity in MRSA induced by special protein aggregates

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  • Shima Tafvizizavareh, National Institute of Genetic Engineering and Biotechnology, Azad Islamic University
  • ,
  • Parvin Shariati, National Institute of Genetic Engineering and Biotechnology
  • ,
  • Atefeh Sharifirad, National Institute of Genetic Engineering and Biotechnology, Pasteur Institute of Iran
  • ,
  • Behnam Maleki, National Institute of Genetic Engineering and Biotechnology, Shahid Sadoughi University of Medical Sciences
  • ,
  • Farhang Aliakbari, National Institute of Genetic Engineering and Biotechnology
  • ,
  • Guanna Christiansen
  • Dina Morshedi, National Institute of Genetic Engineering and Biotechnology

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 μM to <20 μM when using aggregates. Scanning and transition electron micrographs showed completely disrupted cells when treated with aggregated protein/Ox (20 μM). The assisting role of aggregates to induce antibiotic hypersensitivity was continuous and stable, but sub-inhibitory antibiotic concentration (20 μM) 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 μM) relative to Ox (20 μM). This observation can be a breakthrough in finding alternatives where antibiotic dosage can be significantly reduced, thereby preventing emergence of new multidrug-resistant bacteria.

OriginalsprogEngelsk
TidsskriftInternational Journal of Biological Macromolecules
Vol/bind137
Sider (fra-til)528-536
Antal sider9
ISSN0141-8130
DOI
StatusUdgivet - 2019

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