Stress-Induced Mutagenesis, Gambler Cells, and Stealth Targeting Antibiotic-Induced Evolution.
Stress-Induced Mutagenesis, Gambler Cells, and Stealth Targeting Antibiotic-Induced Evolution.
复制标题
作者：
抗生素耐药性的进化和进化机制既是根本性的，也是世界性的健康问题。应激诱导突变定义了由应激反应上调的突变机制，当细胞在应激状态下对环境不适应时，该机制会驱动适应。在抗生素诱导的突变方面的工作已经产生了诱人的线索，但没有连贯的机制。我们综述了抗生素诱导的突变的最新进展，这些突变整合了活性氧(ROS)、SOS和一般应激反应以及多染色体细胞如何协调应激反应诱导的DNA断裂从高保真到突变修复的转换。此外，在兄弟细胞保持稳定的同时，差异产生的ROS诱导了一个可变的“赌徒”细胞亚群，这是一般应激反应的信号。我们讨论了其他可进化的亚群，并将不同的进化促进分子视为药物的潜在靶点，以减缓抗生素耐药性、交叉耐药性和免疫逃避的进化。FDA批准的一种药物是“隐形”进化的例证--减缓了避免选择对自身或抗生素产生耐药性的药物。
Mechanisms of evolution and evolution of antibiotic resistance are both fundamental and world health problems. Stress-induced mutagenesis defines mechanisms of mutagenesis upregulated by stress responses, which drive adaptation when cells are maladapted to their environments—when stressed. Work in mutagenesis induced by antibiotics had produced tantalizing clues but not coherent mechanisms. We review recent advances in antibiotic-induced mutagenesis that integrate how reactive oxygen species (ROS), the SOS and general stress responses, and multichromosome cells orchestrate a stress response-induced switch from high-fidelity to mutagenic repair of DNA breaks. Moreover, while sibling cells stay stable, a mutable “gambler” cell subpopulation is induced by differentially generated ROS, which signal the general stress response. We discuss other evolvable subpopulations and consider diverse evolution-promoting molecules as potential targets for drugs to slow evolution of antibiotic resistance, cross-resistance, and immune evasion. An FDA-approved drug exemplifies “stealth” evolution-slowing drugs that avoid selecting resistance to themselves or antibiotics.
登录
查看更多内容
影响因子：
3.7
作者：
Bunnell, Bryan E.;Escobar, Jillian F.;Crane, John K.
通讯作者：
Crane, John K.
影响因子：
56.9
作者：
Cipponi, Arcadi;Goode, David L.;Thomas, David M.
通讯作者：
Thomas, David M.
影响因子：
10.5
作者：
Battesti A;Majdalani N;Gottesman S
通讯作者：
Gottesman S
影响因子：
9.8
作者：
Cirz, RT;Chin, JK;Romesberg, FE
通讯作者：
Romesberg, FE
影响因子：
46.9
作者：
通讯作者：
--