Institute of Microbiology, Friedrich Schiller University, 07745, Jena, Germany.
Faculty of Biology, Ludwig-Maximilians-University of Munich, 82152, Martinsried, Germany.
Nat Commun. 2020 Nov 27;11(1):6067. doi: 10.1038/s41467-020-19890-8.
Vibrio cholerae, the cause of cholera disease, exhibits a characteristic curved rod morphology, which promotes infectivity and motility in dense hydrogels. Periplasmic protein CrvA determines cell curvature in V. cholerae, yet the regulatory factors controlling CrvA are unknown. Here, we discover the VadR small RNA (sRNA) as a post-transcriptional inhibitor of the crvA mRNA. Mutation of vadR increases cell curvature, whereas overexpression has the inverse effect. We show that vadR transcription is activated by the VxrAB two-component system and triggered by cell-wall-targeting antibiotics. V. cholerae cells failing to repress crvA by VadR display decreased survival upon challenge with penicillin G indicating that cell shape maintenance by the sRNA is critical for antibiotic resistance. VadR also blocks the expression of various key biofilm genes and thereby inhibits biofilm formation in V. cholerae. Thus, VadR is an important regulator for synchronizing peptidoglycan integrity, cell shape, and biofilm formation in V. cholerae.
霍乱弧菌是霍乱病的病原体，呈特征性弯曲杆状形态，这促进了其在高密度水凝胶中的感染力和迁移能力。周质蛋白 CrvA 决定霍乱弧菌的细胞曲率，但控制 CrvA 的调节因子尚不清楚。在这里，我们发现 VadR 小 RNA（sRNA）是 crvA mRNA 的转录后抑制剂。vadR 突变会增加细胞曲率，而过表达则会产生相反的效果。我们表明，vadR 转录受 VxrAB 双组分系统激活，并由细胞壁靶向抗生素触发。vadR 不能抑制 crvA 的 V. cholerae 细胞在受到青霉素 G 挑战时存活能力下降，表明 sRNA 通过维持细胞形状来抵抗抗生素至关重要。VadR 还会阻断各种关键生物膜基因的表达，从而抑制霍乱弧菌的生物膜形成。因此，VadR 是霍乱弧菌中同步肽聚糖完整性、细胞形状和生物膜形成的重要调节剂。
