Hossain Tahmina, Deter Heather S, Peters Eliza J, Butzin Nicholas C
Department of Biology and Microbiology, South Dakota State University, Brookings, SD 57006, USA.
Department of Bioengineering, University of Illinois Urbana-Champaign, Urbana, IL 61801, USA.
iScience. 2021 Apr 3;24(5):102391. doi: 10.1016/j.isci.2021.102391. eCollection 2021 May 21.
Antibiotic resistance is a growing problem, but bacteria can evade antibiotic treatment via tolerance and persistence. Antibiotic persisters are a small subpopulation of bacteria that tolerate antibiotics due to a physiologically dormant state. Hence, persistence is considered a major contributor to the evolution of antibiotic-resistant and relapsing infections. Here, we used the synthetically developed minimal cell JCVI-Syn3B to examine essential mechanisms of antibiotic survival. The minimal cell contains only 473 genes, and most genes are essential. Its reduced complexity helps to reveal hidden phenomenon and fundamental biological principles can be explored because of less redundancy and feedback between systems compared to natural cells. We found that Syn3B evolves antibiotic resistance to different types of antibiotics expeditiously. The minimal cell also tolerates and persists against multiple antibiotics. It contains a few already identified persister-related genes, although lacking many systems previously linked to persistence (e.g. toxin-antitoxin systems, ribosome hibernation genes).
抗生素耐药性是一个日益严重的问题，但细菌可以通过耐受性和持留性来逃避抗生素治疗。抗生素持留菌是一小部分由于生理休眠状态而耐受抗生素的细菌亚群。因此，持留性被认为是抗生素耐药性和复发性感染演变的主要因素。在这里，我们使用合成开发的最小细胞JCVI-Syn3B来研究抗生素存活的基本机制。最小细胞仅包含473个基因，且大多数基因是必需的。其降低的复杂性有助于揭示隐藏的现象，并且由于与天然细胞相比系统之间的冗余和反馈较少，因此可以探索基本的生物学原理。我们发现Syn3B能迅速对不同类型的抗生素产生耐药性。最小细胞也能耐受多种抗生素并持续存在。它包含一些已经确定的与持留菌相关的基因，尽管缺乏许多先前与持留性相关的系统（例如毒素-抗毒素系统、核糖体休眠基因）。
