[대학원 생명과학과 세미나 안내]
연사 : 최상호 교수(서울대학교 식품공학과)
연제 : Targeting Virulence rather than Growth of Pathogenic Bacteria: A Strategy to Develop New Antibiotics without Inducing Resistance
일시 : 2018년 3월 23일 (금) 오후 5시
장소 : 하나과학관 A동 B131호
초청교수 : 김태성 교수
Abstract
Pathogenic Vibrio species cause diseases in diverse marine animals reared in aquaculture. Since their pathogenesis, persistence, and survival in marine environments are regulated by quorum-sensing (QS), QS interference has attracted attention as a means to control these bacteria in aquatic settings. A few QS inhibitors against Vibrio species have been reported, but detailed molecular mechanisms are lacking. Here, we identified a novel, potent, and selective Vibrio QS inhibitor, named QStatin [1-(5-bromothiophene-2-sulfonyl)-1H-pyrazole], which affects V. harveyiLuxR homologues, the well-conserved master transcriptional regulators for QS in Vibrio species. Crystallographic and biochemical analyses showed that QStatin binds tightly to a putative ligand-binding pocket in SmcR, the LuxR homologue in V. vulnificus, and changes the flexibility of the protein, thereby altering its transcription regulatory activity. Transcriptome analysis revealed that QStatin results in SmcR dysfunction, affecting the expression of SmcR regulon required for virulence, motility/chemotaxis, and biofilm dynamics. Notably, QStatin attenuated representative QS-regulated phenotypes in various Vibrio species including virulence against the brine shrimp, Artemia franciscana. Together, these results provide molecular insights into the mechanism of action of an effective, sustainable QS inhibitorthat is less susceptible to resistance than other antimicrobial agents and useful in controlling the virulence of Vibriospecies in aquacultures.