近日，广东工业大学环境健康与污染控制研究院、环境科学与工程学院安太成教授团队在细菌抗生素耐药形成机制研究方面取得最新进展，研究成果以《Response mechanisms of resistance in L-form bacteria to different target antibiotics: implications from oxidative stress to metabolism (https://doi.org/10.1016/j.envint.2024.108729)》为题发表在Environment International (2024, 187: 108729) 期刊上。论文的第一作者为硕士生郑玉叶，通讯作者为李桂英教授。该研究通过诱导革兰氏阴性菌大肠杆菌和革兰氏阳性菌枯草芽孢杆菌进入L型细菌状态，探索了L型细菌对不同靶标抗生素的耐药性，并从氧化应激和新陈代谢的角度揭示了L型细菌的耐药机制。

文章链接：https://doi.org/10.1016/j.envint.2024.108729

β-内酰胺类抗生素作用于细菌细胞壁，在杀灭细菌时表现出高度的特异性。在细胞壁靶标的抗生素压力下，细菌可能选择脱落它们的细胞壁，并转化为L型细菌状态以逃避抗生素的杀灭作用。因此，本项主要研究探讨并确定了适用于革兰氏阴性细菌E. coli和革兰氏阳性细菌B. subtilis的L型细菌的最佳诱导条件。值得注意的是，当正常细菌转变为L型细菌状态时，两种细菌对多种抗生素（多粘菌素E、美罗培南、利福平和四环素）都显示出不同程度的抗性增加。E. coli DH5α(CTX)对四环素的抗性提升最为显著，提升到了128倍，而B. subtilis ATCC6633对四环素和多粘菌素E的抗性提升到了32倍。进一步研究表明，L型细菌保持其正常的代谢活性，并且结合其增强的氧化应激作为一种促进L型细菌持续存活的适应性策略。本项研究为深入理解细菌生存策略、抗生素耐药性形成机制提供了理论基础，并且有助于开发创新耐药菌治疗策略以及正确应对全球抗生素耐药的挑战。

图文摘要

英文摘要

Due to the specific action on bacterial cell wall, β-lactam antibiotics have gained widespread usage as they exhibit a high degree of specificity in targeting bacteria, but causing minimal toxicity to host cells. Under antibiotic pressure, bacteria may opt to shed their cell walls and transform into L-form state as a means to evade the antibiotic effects. In this study, we explored and identified diverse optimal conditions for both Gram-negative bacteria (E. coli DH5α (CTX)) and Gram-positive bacteria (B. subtilis ATCC6633), which were induced to L-form bacteria using lysozyme (0.5 ppm) and meropenem (64 ppm). Notably, when bacteria transformed into L-form state, both bacterial strains showed varying degrees of increased resistance to antibiotics polymyxin E, meropenem, rifampicin, and tetracycline. E. coli DH5α (CTX) exhibited the most significant enhancement in resistance to tetracycline, with a 128-fold increase, while B. subtilis ATCC6633 showed a 32-fold increase in resistance to tetracycline and polymyxin E. Furthermore, L-form bacteria maintained their normal metabolic activity, combined with enhanced oxidative stress, served as an adaptive strategy promoting the sustained survival of L-form bacteria. This study provided a theoretical basis for comprehending antibiotic resistance mechanisms, developing innovative treatment strategies, and confronting global antibiotic resistance challenges.

项目资助：本研究受到国家自然科学基金项目(42330702和42122056)，粤桂联合基金重点项目(2020B1515420002)和广东省重点研发计划项目(2020B1111350002)的资助。