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.
Highlights
The discovery of antibiotics has prolonged human life and helped develop a variety of health-related technologies, the overuse of antibiotics has led to the emergence of "superbugs" as bacteria have evolved the means of resisting traditional antibiotics
extracellular vesicles (EVs) from methicillin-resistant Staphylococcus aureus (MRSA) cultured with or without sub-minimum inhibitory concentration (MIC) of ampicillin were purified, and their capability to degrade several β-lactam antibiotics investigated, and their proteomics compared to identified β-lactam antibiotic resistance-related protein constituents
It was found that the production of MRSA EVs increased dose-dependently by ampicillin treatment, and EVs from cultures treated with ampicillin became more potent in degrading β-lactam antibiotics
Summary
The discovery of antibiotics has prolonged human life and helped develop a variety of health-related technologies, the overuse of antibiotics has led to the emergence of "superbugs" as bacteria have evolved the means of resisting traditional antibiotics. Previous studies have reported that exposure to some physiological or environmental stressors such as antibiotic treatment, oxidative stress, and temperature influenced the level of vesicles secretion, and stressors could cause alterations in the composition of v esicles[11,20,21]. Based on these studies, we hypothesize that a physiological stressor such as sub-lethal antibiotics can trigger bacteria secreting EVs with significant changes in the proteome to adapt and survive in the antibiotic stressed environment. The results implicated that E VStrs, which have more proteins that can degrade antibiotics than E VNor, can offer protection to the β-lactam-susceptible S. aureus against lethal β-lactam antibiotic concentrations better than E VNor
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