Vibrio cholerae senses human enteric α-defensin 5 through a CarSR two-component system to promote bacterial pathogenicity

• DOI: 10.1038/s42003-022-03525-3
• Publication Date: 2022-06-08T10:03:24Z
• Authors: Yutao Liu; Tingting Xu; Qian Wang; Junxi Huang; Yangfei Zhu; Xingmei Liu; Ruiying Liu; Bin Yang; Kai Zhou
• Keywords: 0301 basic medicine; alpha-Defensins; Virulence; QH301-705.5; Gene Expression Regulation, Bacterial; Article; 3. Good health; 03 medical and health sciences; Bacterial Proteins; Intestine, Small; Humans; Biology (General); Vibrio cholerae; Transcription Factors

AbstractVibrio cholerae (V. cholerae) is an aquatic bacterium responsible for acute and fatal cholera outbreaks worldwide. When V. cholerae is ingested, the bacteria colonize the epithelium of the small intestine and stimulate the Paneth cells to produce large amounts of cationic antimicrobial peptides (CAMPs). Human defensin 5 (HD-5) is the most abundant CAMPs in the small intestine. However, the role of the V. cholerae response to HD-5 remains unclear. Here we show that HD-5 significantly upregulates virulence gene expression. Moreover, a two-component system, CarSR (or RstAB), is essential for V. cholerae virulence gene expression in the presence of HD-5. Finally, phosphorylated CarR can directly bind to the promoter region of TcpP, activating transcription of tcpP, which in turn activates downstream virulence genes to promote V. cholerae colonization. In conclusion, this study reveals a virulence-regulating pathway, in which the CarSR two-component regulatory system senses HD-5 to activate virulence genes expression in V. cholerae.