气候变化领域集成服务门户(CCPortal): Exopolysaccharide defects cause hyper-thymineless death in Escherichia coli via massive loss of chromosomal DNA and cell lysis

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DOI	10.1073/PNAS.2012254117
	Exopolysaccharide defects cause hyper-thymineless death in Escherichia coli via massive loss of chromosomal DNA and cell lysis
	Pritha Rao T.V.; Kuzminov A.
发表日期	2021
ISSN	00278424
起始页码	33549
结束页码	33560
卷号	117 期号:52
英文摘要	Thymineless death in Escherichia coli thyA mutants growing in the absence of thymidine (dT) is preceded by a substantial resistance phase, during which the culture titer remains static, as if the chromosome has to accumulate damage before ultimately failing. Significant chromosomal replication and fragmentation during the resistance phase could provide appropriate sources of this damage. Alternatively, the initial chromosomal replication in thymine (T)-starved cells could reflect a considerable endogenous dT source, making the resistance phase a delay of acute starvation, rather than an integral part of thymineless death. Here we identify such a low-molecular-weight (LMW)-dT source as mostly dTDP-glucose and its derivatives, used to synthesize enterobacterial common antigen (ECA). The thyA mutant, in which dTDP-glucose production is blocked by the rfbA rffH mutations, lacks a LMW-dT pool, the initial DNA synthesis during T-starvation and the resistance phase. Remarkably, the thyA mutant that makes dTDP-glucose and initiates ECA synthesis normally yet cannot complete it due to the rffC defect, maintains a regular LMW-dT pool, but cannot recover dTTP from it, and thus suffers T-hyperstarvation, dying precipitously, completely losing chromosomal DNA and eventually lysing, even without chromosomal replication. At the same time, its ECA+ thyA parent does not lyse during T-starvation, while both the dramatic killing and chromosomal DNA loss in the ECA-deficient thyA mutants precede cell lysis. We conclude that: 1) the significant pool of dTDP-hexoses delays acute T-starvation; 2) T-starvation destabilizes even nonreplicating chromosomes, while T-hyperstarvation destroys them; and 3) beyond the chromosome, T-hyperstarvation also destabilizes the cell envelope. © 2020 National Academy of Sciences. All rights reserved.
英文关键词	Cell lysis; Chromosome fragmentation; Chromosome replication; DTDP-glucose; Enterobacterial common antigen
语种	英语
scopus关键词	bacterial antigen; bacterial DNA; bacterial polysaccharide; deoxythymidine diphosphate-glucose; enterobacterial common antigen; Escherichia coli protein; glucose; pyrimidine nucleotide; thymidine; thymine; bacterial chromosome; DNA replication; drug effect; Escherichia coli; genetics; metabolism; microbial viability; molecular weight; mutation; physiological stress; Antigens, Bacterial; Chromosomes, Bacterial; DNA Replication; DNA, Bacterial; Escherichia coli; Escherichia coli Proteins; Glucose; Microbial Viability; Molecular Weight; Mutation; Polysaccharides, Bacterial; Stress, Physiological; Thymidine; Thymine; Thymine Nucleotides
来源期刊	Proceedings of the National Academy of Sciences of the United States of America
文献类型	期刊论文
条目标识符	http://gcip.llas.ac.cn/handle/2XKMVOVA/179616
作者单位	Department of Microbiology, University of Illinois at Urbana–Champaign, Urbana, IL 61801, United States
推荐引用方式 GB/T 7714	Pritha Rao T.V.,Kuzminov A.. Exopolysaccharide defects cause hyper-thymineless death in Escherichia coli via massive loss of chromosomal DNA and cell lysis[J],2021,117(52).
APA	Pritha Rao T.V.,&Kuzminov A..(2021).Exopolysaccharide defects cause hyper-thymineless death in Escherichia coli via massive loss of chromosomal DNA and cell lysis.Proceedings of the National Academy of Sciences of the United States of America,117(52).
MLA	Pritha Rao T.V.,et al."Exopolysaccharide defects cause hyper-thymineless death in Escherichia coli via massive loss of chromosomal DNA and cell lysis".Proceedings of the National Academy of Sciences of the United States of America 117.52(2021).