Elevating NagZ Improves Resistance to β-Lactam Antibiotics via Promoting AmpC β-Lactamase in Enterobacter cloacae.
Elevating NagZ Improves Resistance to β-Lactam Antibiotics via Promoting AmpC β-Lactamase in Enterobacter cloacae.
复制标题
提高 NagZ 通过促进阴沟肠杆菌中 AmpC β-内酰胺酶提高对 β-内酰胺抗生素的耐药性
DOI：
10.3389/fmicb.2020.586729
复制
发表时间：
2020
影响因子：
5.2
通讯作者：
Xu Y
中科院分区：
文献类型：
--
作者：
Yang X;Zeng J;Zhou Q;Yu X;Zhong Y;Wang F;Du H;Nie F;Pang X;Wang D;Fan Y;Bai T;Xu Y
Enterobacter cloacae complex (ECC), one of the most common opportunistic pathogens causing multiple infections in human, is resistant to β-lactam antibiotics mainly due to its highly expressed chromosomal AmpC β-lactamase. It seems that regulation of chromosomal AmpC β-lactamase is associated with peptidoglycan recycling. However, underlying mechanisms are still poorly understood. In this study, we confirmed that NagZ, a glycoside hydrolase participating in peptidoglycan recycling in Gram-negative bacteria, plays a crucial role in developing resistance of E. cloacae (EC) to β-lactam antibiotics by promoting expression of chromosomal AmpC β-lactamase. Our data shows that NagZ was significantly up-regulated in resistant EC (resistant to at least one type of the third or fourth generation cephalosporins) compared to susceptible EC (susceptible to all types of the third and fourth generation cephalosporins). Similarly, the expression and β-lactamase activity of ampC were markedly enhanced in resistant EC. Moreover, ectopic expression of nagZ enhanced ampC expression and resistance to β-lactam antibiotics in susceptible EC. To further understand functions of NagZ in β-lactam resistance, nagZ-knockout EC model (ΔnagZ EC) was constructed by homologous recombination. Conversely, ampC mRNA and protein levels were down-regulated, and resistance to β-lactam antibiotics was attenuated in ΔnagZ EC, while specific complementation of nagZ was able to rescue ampC expression and resistance in ΔnagZ EC. More interestingly, NagZ and its hydrolyzates 1,6-anhydromuropeptides (anhMurNAc) could induce the expression of other target genes of AmpR (a global transcriptional factor), which suggested that the promotion of AmpC by NagZ is mediated AmpR activated by anhMurNAc in EC. In conclusion, these findings provide new elements for a better understanding of resistance in EC, which is crucial for the identification of novel potential drug targets.
登录
查看更多内容
影响因子：
4.9
作者：
Huang, Yi-Wei;Hu, Rouh-Mei;Yang, Tsuey-Ching
通讯作者：
Yang, Tsuey-Ching
影响因子：
6.4
作者：
Gomez-Simmonds A;Annavajhala MK;Wang Z;Macesic N;Hu Y;Giddins MJ;O'Malley A;Toussaint NC;Whittier S;Torres VJ;Uhlemann AC
通讯作者：
Uhlemann AC
影响因子：
4.9
作者：
Juan, C;Moyá, B;Oliver, A
通讯作者：
Oliver, A
DOI：
10.1007/978-1-62703-977-2_35
发表时间：
2014-01-01
期刊：
PROTEIN DOWNSTREAM PROCESSING: DESIGN, DEVELOPMENT AND APPLICATION OF HIGH AND LOW-RESOLUTION METHODS
影响因子：
--
作者：
Arora, Sushrut;Ayyar, B. Vijayalakshmi;O'Kennedy, Richard
通讯作者：
O'Kennedy, Richard
DOI：
10.1093/jac/dky317
发表时间：
2018-11-01
期刊：
The Journal of antimicrobial chemotherapy
影响因子：
--
作者：
Ito A;Nishikawa T;Ota M;Ito-Horiyama T;Ishibashi N;Sato T;Tsuji M;Yamano Y
通讯作者：
Yamano Y