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耻垢分枝杆菌的CorA在对结构不相关抗生素产生固有抗性中的作用。

Involvement of CorA of Mycobacterium smegmatis in exerting intrinsic resistance towards structurally unrelated antibiotics.

作者信息

Chatterjee Debasmita, Daya Manasi A R, Rastogi Sumit Kumar, Panda Aditya Prasad, Biju Bayomi, Bhattacharyya Debleena, Ghosh Anindya Sundar

机构信息

Department of Bioscience and Biotechnology, Indian Institute of Technology Kharagpur, Kharagpur, West Bengal 721302, India.

出版信息

J Appl Microbiol. 2024 Dec 2;135(12). doi: 10.1093/jambio/lxae298.

DOI:10.1093/jambio/lxae298
PMID:39657998
Abstract

AIM

Ubiquitous magnesium transporter, CorA of Mycobacterium smegmatis is well known for its role in maintaining magnesium homeostasis. However, little is known about its involvement in exerting antimicrobial resistance. Here, by using molecular genetics, in vivo and in silico studies, we tried to envisage the role of CorA of M. smegmatis in antimicrobial resistance of M. smegmatis and Escherichia coli.

METHODS AND RESULTS

Expression of corA in M. smegmatis and E. coli decreased the susceptibility of the host cells towards various antibiotics and anti-tubercular drugs, which was elucidated by determining minimum inhibitory concentrations using the micro-broth dilution method. The intracellular antibiotic accumulation assay indicated that the host cells expressing corA accumulated less EtBr, norfloxacin, and ofloxacin than the control cells. Moreover, the presence of a sub-inhibitory concentration of Mg2+ further decreased the susceptibility towards the drugs tested. Furthermore, CorA enhanced the biofilm-forming ability of cells expressing it.

CONCLUSION

CorA (MSMEG_5056), a magnesium transporter of M. smegmatis influences the extrusion of multiple structurally unrelated classes of drugs and enhances the biofilm formation of E. coli and M. smegmatis.

摘要

目的

耻垢分枝杆菌的普遍存在的镁转运蛋白CorA以其在维持镁稳态中的作用而闻名。然而,关于其在发挥抗微生物耐药性方面的作用知之甚少。在此,通过分子遗传学、体内和计算机模拟研究,我们试图设想耻垢分枝杆菌的CorA在耻垢分枝杆菌和大肠杆菌的抗微生物耐药性中的作用。

方法与结果

耻垢分枝杆菌和大肠杆菌中corA的表达降低了宿主细胞对各种抗生素和抗结核药物的敏感性,这通过使用微量肉汤稀释法测定最低抑菌浓度得以阐明。细胞内抗生素积累试验表明,表达corA的宿主细胞比对照细胞积累的溴化乙锭、诺氟沙星和氧氟沙星更少。此外,亚抑制浓度的Mg2+的存在进一步降低了对所测试药物的敏感性。此外,CorA增强了表达它的细胞的生物膜形成能力。

结论

耻垢分枝杆菌的镁转运蛋白CorA(MSMEG_5056)影响多种结构不相关类别的药物的外排,并增强大肠杆菌和耻垢分枝杆菌的生物膜形成。

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