Significant increase in the secretion of extracellular vesicles and antibiotics resistance from methicillin-resistant Staphylococcus aureus induced by ampicillin stress

氨苄西林应激诱导耐甲氧西林金黄色葡萄球菌胞外囊泡分泌显著增加及抗生素耐药性

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作者:Si Won Kim, Jong-Su Seo, Seong Bin Park, Ae Rin Lee, Jung Seok Lee, Jae Wook Jung, Jin Hong Chun, Jassy Mary S Lazarte, Jaesung Kim, Jong-Hwan Kim, Jong-Wook Song, Chris Franco, Wei Zhang, Min Woo Ha, Seung-Mann Paek, Myunghwan Jung, Tae Sung Jung

Abstract

Extracellular vesicles (EVs) containing specific cargo molecules from the cell of origin are naturally secreted from bacteria. EVs play significant roles in protecting the bacterium, which can contribute to their survival in the presence of antibiotics. Herein, we isolated EVs from methicillin-resistant Staphylococcus aureus (MRSA) in an environment with or without stressor by adding ampicillin at a lower concentration than the minimum inhibitory concentration (MIC). We investigated whether EVs from MRSA under stress condition or normal condition could defend susceptible bacteria in the presence of several β-lactam antibiotics, and directly degrade the antibiotics. A comparative proteomic approach was carried out in both types of EVs to investigate β-lactam resistant determinants. The secretion of EVs from MRSA under antibiotic stressed conditions was increased by 22.4-fold compared with that of EVs without stress. Proteins related to the degradation of β-lactam antibiotics were abundant in EVs released from the stressed condition. Taken together, the present data reveal that EVs from MRSA play a crucial role in the survival of β-lactam susceptible bacteria by acting as the first line of defense against β-lactam antibiotics, and antibiotic stress leads to release EVs with high defense activity.

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