title: Small-Molecule Inhibitors of the Type III Secretion System.
abstract: Drug-resistant pathogens have presented increasing challenges to the discovery and development of new antibacterial agents. The type III secretion system (T3SS), existing in bacterial chromosomes or plasmids, is one of the most complicated protein secretion systems. T3SSs of animal and plant pathogens possess many highly conserved main structural components comprised of about 20 proteins. Many Gram-negative bacteria carry T3SS as a major virulence determinant, and using the T3SS, the bacteria secrete and inject effector proteins into target host cells, triggering disease symptoms. Therefore, T3SS has emerged as an attractive target for antimicrobial therapeutics. In recent years, many T3SS-targeting small-molecule inhibitors have been discovered; these inhibitors prevent the bacteria from injecting effector proteins and from causing pathophysiology in host cells. Targeting the virulence of Gram-negative pathogens, rather than their survival, is an innovative and promising approach that may greatly reduce selection pressures on pathogens to develop drug-resistant mutations. This article summarizes recent progress in the search for promising small-molecule T3SS inhibitors that target the secretion and translocation of bacterial effector proteins.
authors.affiliation: School of Pharmaceutical Engineering and Life Science, Changzhou University, Changzhou 213164, China. kikyo1210@sina.com.
authors.forename: Lingling
authors.initials: L
authors.lastname: Gu
authors.affiliation: School of Pharmaceutical Engineering and Life Science, Changzhou University, Changzhou 213164, China. sunnychou33@sina.com.
authors.forename: Shanshan
authors.initials: S
authors.lastname: Zhou
authors.affiliation: School of Pharmaceutical Engineering and Life Science, Changzhou University, Changzhou 213164, China. zhulanping91@163.com.
authors.forename: Lanping
authors.initials: L
authors.lastname: Zhu
authors.affiliation: School of Pharmaceutical Engineering and Life Science, Changzhou University, Changzhou 213164, China. Liang_cuirong@163.com.
authors.forename: Cuirong
authors.initials: C
authors.lastname: Liang
authors.affiliation: School of Pharmaceutical Engineering and Life Science, Changzhou University, Changzhou 213164, China. xinchen@cczu.edu.cn.
authors.forename: Xin
authors.initials: X
authors.lastname: Chen
mesh_terms: D000900:Anti-Bacterial Agents / Q000737:chemistry / Q000494:pharmacology*; D024881:Drug Resistance, Bacterial / Q000187:drug effects; D006090:Gram-Negative Bacteria / Q000187:drug effects / Q000378:metabolism; D054852:Small Molecule Libraries / Q000494:pharmacology*; D000069296:Type III Secretion Systems / Q000037:antagonists & inhibitors*; D014774:Virulence / Q000187:drug effects
chemical_list: D000900:Anti-Bacterial Agents; D054852:Small Molecule Libraries; D000069296:Type III Secretion Systems
keywords: Gram-negative bacteria; antibacterial agents; effector proteins; pathogens; small-molecule inhibitors; type III secretion system; virulence