2. Academic Validation
  3. Identification of an anti-Gram-negative bacteria agent disrupting the interaction between lipopolysaccharide transporters LptA and LptC

Identification of an anti-Gram-negative bacteria agent disrupting the interaction between lipopolysaccharide transporters LptA and LptC

  • Int J Antimicrob Agents. 2019 Apr;53(4):442-448. doi: 10.1016/j.ijantimicag.2018.11.016.
Xuelian Zhang 1,  Yan Li 1,  Weiwei Wang 1,  Jing Zhang 1,  Yuan Lin 2,  Bin Hong 1,  Xuefu You 1,  Danqing Song 1,  Yanchang Wang 3,  Jiandong Jiang 4,  Shuyi Si 5
Affiliations

Affiliations

  • 1 Beijing Key Laboratory of Antimicrobial Agents, Institute of Medicinal Biotechnology, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.
  • 2 Beijing Key Laboratory of Antimicrobial Agents, Institute of Medicinal Biotechnology, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China; State Key Laboratory of Bioactive Substance and Function of Natural Medicines, Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.
  • 3 Department of Biomedical Sciences, College of Medicine, Florida State University, Tallahassee, FL, USA. Electronic address: yanchang.wang@med.fsu.edu.
  • 4 Beijing Key Laboratory of Antimicrobial Agents, Institute of Medicinal Biotechnology, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China; State Key Laboratory of Bioactive Substance and Function of Natural Medicines, Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China. Electronic address: jiang.jd@163.com.
  • 5 Beijing Key Laboratory of Antimicrobial Agents, Institute of Medicinal Biotechnology, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China. Electronic address: sisyimb@hotmail.com.
PMID: 30476569 DOI: 10.1016/j.ijantimicag.2018.11.016
Abstract

Introduction: The emergence of drug-resistant Gram-negative bacteria is a serious clinical problem that causes increased morbidity and mortality. However, the slow discovery of new Antibiotics is unable to meet the need for treating Bacterial infections caused by drug-resistant strains. Lipopolysaccharide (LPS) is synthesized in the cytoplasm and transported to the cell envelope by the LPS transport (Lpt) system. LptA and LptC form a complex that transports LPS from the inner membrane to the outer membrane.

Methods: This study performed a screen for agents that disrupt the transport of LPS in Gram-negative bacteria Escherichia coli. It established a yeast two-hybrid system to detect LptA-LptC interaction and used this system to identify a compound, IMB-881, that blocks this interaction and shows Antibacterial activity.

Results: This study demonstrated that the IMB-881 compound specifically binds to LptA to disrupt LptA-LptC interaction using surface plasmon resonance assay. Overproduction of LptA protein but not that of LptC lowered the Antibacterial activity of IMB-881. Strikingly, Escherichia coli cells accumulated 'extra' membrane material in the periplasm and exhibited filament morphology after treatment with IMB-881.

Conclusion: This study successfully identified, by using a yeast two-hybrid system, an Antibacterial agent that likely blocks LPS transport in Gram-negative bacteria.

Keywords

Antibacterial agent; Escherichia coli; Lipopolysaccharide; LptA-LptC interaction; Yeast two-hybrid.

Figures
Products
嗨！很高兴为您提供帮助！

尊敬的 MCE 客户您好，
请您选择所在区域，我们将转接对应客服为您服务！

热门区域

A

B

C

F

G

H

J

L

N

Q

S

T

X

Y

Z

热 A B C F G H J L N Q S T X Y Z