Zhang Yating, Dai Shuo, Zhu Xiaobin, Dai Ying, Li Guoming, Du Xiaoli, Li Yirong, Xiao Xiao
Department of Laboratory Medicine, Zhongnan Hospital of Wuhan University, Wuhan, China.
Institute of Health Inspection and Testing, Hubei Provincial Center for Disease Control and Prevention, Wuhan, China.
iScience. 2025 Mar 28;28(5):112311. doi: 10.1016/j.isci.2025.112311. eCollection 2025 May 16.
species are emerging multidrug-resistant pathogens with inconsistent carbapenem susceptibility, being resistant to meropenem but susceptible to imipenem, which complicates treatment. Here, we identified a previously uncharacterized oxacillinase gene, , in 12 strains from Wuhan, China. Deleting reduced meropenem and imipenem minimal inhibitory concentrations (MICs) by 64- and 4-fold, respectively, while reintroducing it into and restored resistance. Mechanistically, OXA-1152 exhibited stronger binding and hydrolysis efficiency for meropenem than imipenem. Combining avibactam with carbapenems restored susceptibility to meropenem and further reduced imipenem MICs, highlighting OXA-1152's role in resistance variation. These findings reveal the molecular basis of carbapenem resistance discrepancy in and suggest avibactam-carbapenem combinations as a promising therapeutic strategy, offering broader implications for treating multidrug-resistant infections.
这些菌株是正在出现的多重耐药病原体，对碳青霉烯类药物的敏感性不一致，对美罗培南耐药但对亚胺培南敏感，这使治疗变得复杂。在此，我们在中国武汉的12株菌株中鉴定出一个先前未被表征的氧青霉烷酶基因。删除该基因分别使美罗培南和亚胺培南的最低抑菌浓度（MIC）降低了64倍和4倍，而将其重新导入菌株中则恢复了耐药性。从机制上讲，OXA-1152对美罗培南的结合和水解效率比亚胺培南更强。将阿维巴坦与碳青霉烯类药物联合使用可恢复对美罗培南的敏感性，并进一步降低亚胺培南的MIC，突出了OXA-1152在耐药性变异中的作用。这些发现揭示了该菌株碳青霉烯类耐药差异的分子基础，并表明阿维巴坦-碳青霉烯类药物联合使用是一种有前景的治疗策略，对治疗多重耐药感染具有更广泛的意义。
