Gao Can, Jiang Kun, Qi Jiaxin, Zheng Chang, Liang Yanli
Department of Clinical Laboratory, Suining Central Hospital, Suining, Sichuan, People's Republic of China.
Infect Drug Resist. 2025 Jun 27;18:3175-3185. doi: 10.2147/IDR.S523844. eCollection 2025.
Multidrug-resistant (MDR-) is on the rise, making it challenging to achieve the desired therapeutic effects with existing conventional antibiotics. The search for new antibacterial targets has emerged as a significant research focus.
The lysophospholipid acyltransferases (LPLATs) proteins encoded by the lpxM gene play a pivotal role in the biosynthesis of lipopolysaccharides (LPS). LPS is a critical component of the outer membrane of the cell wall and is essential for the survival and drug resistance of Gram-negative bacteria. This study aims to investigate the effects of the lpxM gene on the growth and drug susceptibility of MDR-.
The standard strain of () s selected as the target. The lpxM gene was knocked out using the pyrF/5-FOA-based counterselectable method. Subsequently, the growth status and the minimum inhibitory concentration (MIC) of the knockout strain against conventional antibiotics were compared.
The lpxM gene in AYE was successfully and fully knocked out. The absorbance value at OD600 for the lpxM knockout strain during the stable period was observed to be as low as 2.5, indicating a significant reduction in growth rate. Furthermore, the MIC of the knockout strain for imipenem decreased from 16 μg/mL to 1 μg/mL, and the MIC for ceftazidime decreased from 32 μg/mL to 16 μg/mL, enhancing antibiotic sensitivity.
This study demonstrates that the deletion of the lpxM gene induces alterations in the growth and drug resistance of , providing a crucial foundation for further investigation into the mechanisms underlying LPS-mediated drug resistance and for the screening of effective auxiliary inhibitors targeting lpxM against MDR-.
多重耐药菌（MDR -）正在增加，使用现有的传统抗生素实现理想的治疗效果具有挑战性。寻找新的抗菌靶点已成为一个重要的研究重点。
由lpxM基因编码的溶血磷脂酰转移酶（LPLATs）蛋白在脂多糖（LPS）的生物合成中起关键作用。LPS是细胞壁外膜的关键成分，对革兰氏阴性菌的存活和耐药性至关重要。本研究旨在探讨lpxM基因对MDR -生长和药敏性的影响。
选择（）的标准菌株作为靶点。使用基于pyrF/5 - FOA的反选择方法敲除lpxM基因。随后，比较敲除菌株的生长状态和对传统抗生素的最低抑菌浓度（MIC）。
AYE中的lpxM基因被成功且完全敲除。观察到lpxM敲除菌株在稳定期OD600处的吸光度值低至2.5，表明生长速率显著降低。此外，敲除菌株对亚胺培南的MIC从16μg/mL降至1μg/mL，对头孢他啶的MIC从32μg/mL降至16μg/mL，增强了抗生素敏感性。
本研究表明，lpxM基因的缺失诱导了（此处原文缺失具体菌名）生长和耐药性的改变，为进一步研究LPS介导的耐药机制以及筛选针对MDR -的靶向lpxM的有效辅助抑制剂提供了关键基础。
