Assessing the Potential of Gallic Acid and Methyl Gallate to Enhance the Efficacy of β-Lactam Antibiotics against Methicillin-Resistant Staphylococcus aureus by Targeting β-Lactamase: In Silico and In Vitro Studies

被引:13
作者
Jiamboonsri, Pimsumon [1 ]
Eurtivong, Chatchakorn [2 ]
Wanwong, Sompit [3 ]
机构
[1] King Mongkuts Inst Technol Ladkrabang, Fac Engn, 1 Chalongkrung Rd, Bangkok 10520, Thailand
[2] Mahidol Univ, Fac Pharm, Dept Pharmaceut Chem, 447 Si Ayudhaya Rd, Bangkok 10400, Thailand
[3] King Mongkuts Univ Technol Thonburi, Sch Energy Environm & Mat, Mat Technol Program, 126 Pracha Uthit Rd, Bangkok 10140, Thailand
来源
ANTIBIOTICS-BASEL | 2023年 / 12卷 / 11期
关键词
gallic acid; methyl gallate; methicillin-resistant Staphylococcus aureus; beta-lactamase; beta-lactam antibiotics; MOLECULAR DOCKING; INHIBITION; COMBINATION;
D O I
10.3390/antibiotics12111622
中图分类号
R51 [传染病];
学科分类号
100401 ;
摘要
Methicillin-resistant Staphylococcus aureus (MRSA), a global health concern, has prompted research into antibiotic adjuvants as a potential solution. Although our group previously reported the enhancing effects of gallic acid (GA) and methyl gallate (MG) on penicillin G activity against MRSA, the synergistic potential with other beta-lactam antibiotics and the underlying mechanism have not been fully explored. Therefore, this study primarily aimed to investigate the antibacterial synergism with beta-lactam antibiotics through disc diffusion, checkerboard, and time-kill assays. The beta-lactamase inhibition was also examined through both molecular modeling and in vitro experiments. Additionally, bacterial morphology changes were studied using a scanning electron microscopy (SEM). The results revealed that both GA and MG exhibited anti-MRSA activity and showed indifferent effects when combined with beta-lactam antibiotics against methicillin susceptible S. aureus (MSSA). Interestingly, MG demonstrated synergism with only the beta-lactamase-unstable antibiotics against MRSA with the lowest fractional inhibitory concentration (FIC) indexes of <= 3.75. However, GA and MG exhibited weak beta-lactamase inhibition. Furthermore, GA, MG, and the combination with ampicillin induced the morphological changes in MRSA, suggesting a possible mechanism affecting the cell membrane. These findings suggest that MG could potentially serve as an adjunct to beta-lactam antibiotics to combat MRSA infections.
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页数:17
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