Identification of Novel Genes Involved in Escherichia coli Persistence to Tosufloxacin.
Identification of Novel Genes Involved in Escherichia coli Persistence to Tosufloxacin.
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大肠杆菌对托舒沙星耐药性相关新基因的鉴定
DOI：
10.3389/fcimb.2020.581986
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发表时间：
2020
影响因子：
5.7
通讯作者：
Niu H
中科院分区：
文献类型：
--
作者：
Li T;Wang J;Cao Q;Li F;Han J;Zhu B;Zhang Y;Niu H
持留菌是野生型的代谢静止表型变体，其耐受杀生物抗生素，并且持留菌形成和存活的机制是复杂的并且未完全理解。为了鉴定与托舒沙星持久性有关的基因，托舒沙星比大多数其他喹诺酮类药物具有更高的抗持久性活性，我们筛选了E。coli KEIO突变体文库，使用与大多数持久突变体筛选（6 h）不同的条件，用托舒沙星更长的暴露18 h。我们鉴定了18个突变体（acrA、acrB、ddlB、dnaG、gltI、hlpA、lpcA、recG、recN、rfaH、ruvC、surA、tatC、tolQ、uvrD、xseA和tetrafI），它们不能形成托氟沙星耐受持久突变体。其中，gltI、hlpA、ruvC、ddlB、tagfI和tatC是大肠杆菌特有的基因。大肠杆菌对托舒沙星的持久性未见报道。此外，缺失突变体的基因编码周质蛋白（surA，lpcA，hlpA，和gltI）有更多的缺陷，持久性托舒沙星比其他已确定的突变体，surA和lpcA突变体是最突出的。surA和lpcA突变体的“深”持久表型在体外和体内得到进一步证实。与野生型菌株E. coliBW 25113中，surA和lpcA突变体的持久表型在各种抗生素、酸性、高渗和热条件下的持久性降低100- 1，000倍以上。此外，在静止期细菌和生物膜细菌感染小鼠模型中，surA和lpcA突变体的存活率和持久性低于亲本尿路致病性菌株UTI 89，表明体外鉴定的持久性机制（surA和lpcA）对于体内持久性是有效的和有效的。我们的研究结果提供了新的见解持续形成和维持托舒沙星的机制，并可能提供新的治疗和疫苗的目标，开发更有效的治疗和预防持久性大肠杆菌。大肠杆菌感染。
Persisters are metabolically quiescent phenotypic variants of the wild type that are tolerant to cidal antibiotics, and the mechanisms of persister formation and survival are complex and not completely understood. To identify genes involved in persistence to tosufloxacin, which has higher activity against persisters than most other quinolones, we screened the E. coli KEIO mutant library using a different condition from most persister mutant screens (6 h) with a longer exposure of 18 h with tosufloxacin. We identified 18 mutants (acrA, acrB, ddlB, dnaG, gltI, hlpA, lpcA, recG, recN, rfaH, ruvC, surA, tatC, tolQ, uvrD, xseA, and ydfI) that failed to form tosufloxacin tolerant persisters. Among them, gltI, hlpA, ruvC, ddlB, ydfI, and tatC are unique genes involved in E. coli persistence to tosufloxacin which have not been reported before. Furthermore, deletion mutants in genes coding periplasmic proteins (surA, lpcA, hlpA, and gltI) had more defect in persistence to tosufloxacin than the other identified mutants, with surA and lpcA mutants being the most prominent. The “deep” persister phenotype of surA and lpcA mutants was further confirmed both in vitro and in vivo. Compared with the wild type strain E. coli BW25113 in vitro, the persister phenotype of the surA and lpcA mutants was decreased more than 100–1,000-fold in persistence to various antibiotics, acidic, hyperosmotic and heat conditions. In addition, in both stationary phase bacteria and biofilm bacteria infection mouse models, the surA and lpcA mutants had lower survival and persistence than the parent uropathogenic strain UTI89, suggesting that the in vitro identified persister mechanisms (surA and lpcA) are operative and valid for in vivo persistence. Our findings provide new insight into the mechanisms of persister formation and maintenance under tosufloxacin and will likely provide novel therapeutic and vaccine targets for developing more effective treatment and prevention of persistent E. coli infections.
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影响因子：
11.4
作者：
Martinez, JJ;Mulvey, MA;Hultgren, SJ
通讯作者：
Hultgren, SJ
DOI：
10.3390/antibiotics4020179
发表时间：
2015-05-12
期刊：
Antibiotics (Basel, Switzerland)
影响因子：
--
作者：
Niu H;Cui P;Shi W;Zhang S;Feng J;Wang Y;Sullivan D;Zhang W;Zhu B;Zhang Y
通讯作者：
Zhang Y
DOI：
10.1073/pnas.120163297
发表时间：
2000-06-06
影响因子：
11.1
作者：
Datsenko, KA;Wanner, BL
通讯作者：
Wanner, BL
影响因子：
3.6
作者：
Korch, SB;Henderson, TA;Hill, TM
通讯作者：
Hill, TM
影响因子：
3.5
作者：
KAHANE, S;MARCUS, M;KABACK, HR
通讯作者：
KABACK, HR