Faculty of Health Sciences, University of Macau, Macau SAR, People's Republic of China.
Department of Molecular and Cellular Biochemistry, Indiana University, Bloomington, IN, USA.
Emerg Microbes Infect. 2020 Dec;9(1):1149-1159. doi: 10.1080/22221751.2020.1770630.
Bacterial persistence is one of the major causes of antibiotic treatment failure and the step stone for antibiotic resistance. However, the mechanism by which persisters arise has not been well understood. Maintaining a dormant state to prevent antibiotics from taking effect is believed to be the fundamental mechanistic basis, and persisters normally maintain an intact cellular structure. Here we examined the morphologies of persisters in survived from the treatment by three major classes of antibiotics (i.e. -lactam, aminoglycoside, and fluoroquinolone) with microcopy and found that a fraction of enlarged spherical bacteria constitutes a major sub-population of bacterial survivors from -lactam antibiotic treatment, whereas survivors from the treatment of aminoglycoside and fluoroquinolone were less changed morphologically. Further studies showed that these spherical bacteria had completely lost their cell wall structures but could survive without any osmoprotective reagent. The spherical bacteria were not the viable-but-non-culturable cells and they could revive upon the removal of -lactam antibiotics. Importantly, these non-walled spherical bacteria also persisted during antibiotic therapy using as the infection model. Additionally, the combinational treatment on by -lactam and membrane-targeting antibiotic significantly enhanced the killing efficacy. Our results indicate that in addition to the dormant, structure intact persisters, the non-wall spherical bacterium is another important type of persister in The finding suggests that targeting the bacterial cell membrane during -lactam chemotherapy could enhance therapeutic efficacy on infection, which might also help to reduce the resistance development of .
细菌持续存在是抗生素治疗失败的主要原因之一，也是抗生素耐药性产生的踏脚石。然而，持久菌产生的机制尚未得到很好的理解。人们认为，保持休眠状态以防止抗生素发挥作用是其基本的机械基础，而持久菌通常保持完整的细胞结构。在这里，我们通过显微镜检查了从三种主要类别的抗生素（即β-内酰胺类、氨基糖苷类和氟喹诺酮类）治疗中幸存下来的持久菌的形态，发现一部分放大的球形细菌构成了β-内酰胺类抗生素治疗后细菌幸存者的主要亚群，而氨基糖苷类和氟喹诺酮类治疗后的幸存者在形态上变化较小。进一步的研究表明，这些球形细菌完全失去了细胞壁结构，但在没有任何渗透压保护剂的情况下仍能存活。这些球形细菌不是活而不能培养的细胞，在β-内酰胺类抗生素去除后可以复活。重要的是，这些无壁球形细菌在使用 作为感染模型的抗生素治疗期间也能持续存在。此外，β-内酰胺和膜靶向抗生素联合治疗对 的杀伤效果显著增强。我们的结果表明，除了休眠的、结构完整的持久菌外，无壁球形细菌也是 中的另一种重要的持久菌类型。这一发现表明，在β-内酰胺化疗期间靶向细菌细胞膜可以提高对 感染的治疗效果，这也可能有助于减少 的耐药性发展。
