Vibrio cholerae causes cholera, an important cause of death worldwide. A fuller understanding of how virulence is regulated offers the potential for developing virulence inhibitors, regarded as efficient therapeutic alternatives for cholera treatment. Here we show using competitive infections of wild-type and mutant bacteria that the regulator of chitosan utilization, ChsR, increases V. cholerae virulence in vivo. Mechanistically, RNA sequencing, chromatin immunoprecipitation with sequencing and molecular biology approaches revealed that ChsR directly upregulated the expression of the virulence regulator, TcpP, which promoted expression of the cholera toxin and the toxin co-regulated pilus, in response to low O₂ levels in the small intestine. We also found that chitosan degradation products inhibit the ChsR–tcpP promoter interaction. Consistently, administration of chitosan oligosaccharide, particularly when delivered via sodium alginate microsphere carriers, reduced V. cholerae intestinal colonization and disease severity in mice by blocking the chsR-mediated pathway. These data reveal the potential of chitosan oligosaccharide as supplemental therapy for cholera treatment and prevention.

霍乱弧菌可引起霍乱，霍乱是世界范围内导致死亡的重要原因。更全面地了解毒力如何调节为开发毒力抑制剂提供了潜力，毒力抑制剂被认为是霍乱治疗的有效替代疗法。在这里，我们使用野生型和突变型细菌的竞争性感染表明，壳聚糖利用的调节因子 ChsR 增加了霍乱弧菌在体内的毒力。从机制上讲，RNA 测序、染色质免疫沉淀与测序和分子生物学方法显示，ChsR 直接上调毒力调节因子 TcpP 的表达，该调节因子促进霍乱毒素和毒素共同调节菌毛的表达，以响应小肠中的低 O₂ 水平。我们还发现壳聚糖降解产物抑制 ChsR-tcpP 启动子相互作用。一致地，壳聚糖低聚糖的给药，特别是通过海藻酸钠微球载体递送时，通过阻断 chsR 介导的通路减少了小鼠霍乱弧菌肠道定植和疾病严重程度。这些数据揭示了壳寡糖作为霍乱治疗和预防补充疗法的潜力。