TY - JOUR
T1 - Antibiotic hypersensitivity in MRSA induced by special protein aggregates
AU - Tafvizizavareh, Shima
AU - Shariati, Parvin
AU - Sharifirad, Atefeh
AU - Maleki, Behnam
AU - Aliakbari, Farhang
AU - Christiansen, Guanna
AU - Morshedi, Dina
N1 - Copyright © 2019. Published by Elsevier B.V.
PY - 2019
Y1 - 2019
N2 - 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.
AB - 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.
KW - Animals
KW - Anti-Bacterial Agents/pharmacology
KW - Drug Resistance, Multiple, Bacterial/drug effects
KW - Drug Synergism
KW - Methicillin-Resistant Staphylococcus aureus/drug effects
KW - Microbial Sensitivity Tests
KW - Microbial Viability/drug effects
KW - Muramidase/chemistry
KW - Oxacillin/pharmacology
KW - Protein Aggregates
UR - http://www.scopus.com/inward/record.url?scp=85068443685&partnerID=8YFLogxK
U2 - 10.1016/j.ijbiomac.2019.07.001
DO - 10.1016/j.ijbiomac.2019.07.001
M3 - Journal article
C2 - 31271798
AN - SCOPUS:85068443685
SN - 0141-8130
VL - 137
SP - 528
EP - 536
JO - International Journal of Biological Macromolecules
JF - International Journal of Biological Macromolecules
ER -