首页|谷氨酸逆转副溶血弧菌氧氟沙星耐药性的研究

谷氨酸逆转副溶血弧菌氧氟沙星耐药性的研究

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细菌耐药已经成为国际社会面临的重大公共卫生挑战,不仅严重危害人类健康,而且制约水产养殖业的可持续发展,迫切需要解决抗生素耐药性问题.尽管对细菌耐药机制的认识不断完善,但仍缺乏有效的控制策略.本文以严重危害我国水产养殖业的副溶血弧菌为研究对象,开展代谢逆转氧氟沙星耐药性的研究.选择副溶血弧菌(Vibrio parahaemolyticus ATCC17802)为实验对象,通过人工传代筛选氧氟沙星耐药菌.采用GC-MS代谢组学的方法比较了副溶血弧菌敏感菌和耐药菌的代谢特征;进一步分析敏感菌与耐药菌的差异代谢特征,筛选出11条差异代谢通路,并鉴定到谷氨酸为关键生物标志物.外源谷氨酸能够有效逆转副溶血弧菌对氧氟沙星的耐药性,提高抗生素的体外杀菌率30倍,并且这种逆转效力不仅对副溶血弧菌有效,对其他临床分离的耐药弧菌菌株也具有很好的效果.进一步对谷氨酸促进氧氟沙星杀菌作用机制的研究发现,谷氨酸是通过代谢调节质子动力势(proton motive force,PMF)介导的胞内抗生素浓度增加来发挥作用的.本研究拓展了代谢调节细菌耐药性的认识,为建立利用现有抗生素对抗水产耐药菌感染奠定了研究基础.
The study of glutamate reversing ofloxacin resistance in Vibrio parahaemolyticus
Bacterial resistance has become a significant public health challenge facing the international community,not only seriously endangering human health but also constraining the sustainable development of aquaculture.It is urgently needed to address the issue of antibiotic resistance.Although the understanding of bacterial resistance mechanisms continues to improve,effective control strategies are still lacking.This study focuses on the research of metabolism reversal of ofloxacin resistance in Vibrio parahaemolyticus,which seriously harms China's aquaculture industry.Vibrio parahaemolyticus ATCC17802 was selected as the experimental strain,and ofloxacin-resistant bacteria were screened by artificial passage.Using GC-MS metabolomics,the metabolic characteristics of sensitive and resistant strains of Vibrio parahaemolyticus were compared.Further analysis of the differential metabolic characteristics between sensitive and resistant strains identified 11 differential metabolic pathways,with glutamate identified as a key biomarker.Exogenous glutamate metabolism reprogramming can effectively reverse the resistance of Vibrio parahaemolyticus to ofloxacin,increasing the in vitro bactericidal rate of antibiotics by 30-fold.Moreover,this reversal effect is not only effective against Vibrio parahaemolyticus but also shows promising results against other clinically isolated antibiotic-resistant vibrio strains.Further research on the mechanism of glutamate promoting ofloxacin bactericidal action revealed that the reversal of resistance in Vibrio parahaemolyticus by glutamate is achieved through metabolic regulation mediated by increased intracellular antibiotic concentration due to proton motive force(PMF).This study expands the understanding of metabolic regulation of bacterial resistance and lays the research foundation for establishing the use of existing antibiotics to combat antibiotic-resistant infections in aquaculture.

Vibrio parahaemolyticusofloxacinglutamatemetabolic regulationproton motive force

寇天顺、殷悦、沈竹清、彭博

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中山大学生命科学学院,水产动物疫病防控与健康养殖全国重点实验室,广州 510275

副溶血弧菌 氧氟沙星 谷氨酸 代谢调控 质子动力势

国家自然科学基金

32061133007

2024

中国科学(生命科学)
中国科学院

中国科学(生命科学)

CSTPCD北大核心
影响因子:0.725
ISSN:1674-7232
年,卷(期):2024.54(9)