当前位置: X-MOL 学术iScience › 论文详情
A Strategic Target Rescues Trimethoprim Sensitivity in Escherichia coli.
iScience ( IF 4.447 ) Pub Date : 2020-03-16 , DOI: 10.1016/j.isci.2020.100986
Amrisha Bhosle,Akshay Datey,Giridhar Chandrasekharan,Deepshikha Singh,Dipshikha Chakravortty,Nagasuma Chandra

Trimethoprim, a preferred treatment for urinary tract infections, is becoming obsolete owing to the rapid dissemination of resistant E. coli. Although direct resistance mechanisms such as overexpression of a mutant FolA and dfr enzymes are well characterized, associated alterations that drive or sustain resistance are unknown. We identify the repertoire of resistance-associated perturbations by constructing and interrogating a transcriptome-integrated functional interactome. From the cross talk between perturbations in stress-response and metabolic pathways, we identify the critical dependence on serine hydroxymethyltransferase (GlyA) as an emergent vulnerability. Through its deletion, we demonstrate that GlyA is necessary to sustain high levels of resistance in both laboratory-evolved resistant E. coli and a multidrug-resistant clinical isolate. Through comparative evolution, we show that the absence of GlyA activity decelerates the acquisition of resistance in E. coli. Put together, our results identify GlyA as a promising target, providing a basis for the rational design of drug combinations.
更新日期:2020-03-16

 

全部期刊列表>>
欢迎访问IOP中国网站
自然职场线上招聘会
GIANT
产业、创新与基础设施
自然科研线上培训服务
材料学研究精选
胸腔和胸部成像专题
屿渡论文,编辑服务
何川
苏昭铭
陈刚
姜涛
李闯创
李刚
北大
跟Nature、Science文章学绘图
隐藏1h前已浏览文章
中洪博元
课题组网站
新版X-MOL期刊搜索和高级搜索功能介绍
ACS材料视界
x-mol收录
上海纽约大学
张健
陈芬儿
厦门大学
李祥
吉林大学
卓春祥
张昊
杨中悦
试剂库存
天合科研
down
wechat
bug