Krishnan H H, Ghosh Amalendu, Paul Kalidas, Chowdhury Rukhsana
Biophysics Division, Indian Institute of Chemical Biology, 4 Raja S. C. Mullick Road, Calcutta 700 032, India.
Infect Immun. 2004 Jul;72(7):3961-7. doi: 10.1128/IAI.72.7.3961-3967.2004.
In Vibrio cholerae, the transmembrane DNA binding proteins, ToxR and TcpP, activate expression of the regulatory gene toxT in response to specific environmental signals. The resulting enhanced level of ToxT leads to a coordinated increase in the production of a subset of virulence factors, including cholera toxin (CT) and toxin-coregulated pilus (TCP). The effect of anaerobiosis on expression of the V. cholerae virulence regulatory cascade was examined. The expression of the major regulatory genes, tcpP, toxR, and toxT, in anaerobically grown V. cholerae was comparable to that in cells grown under aerobic conditions, and no significant difference in the ToxT-dependent expression of tcpA was detected when aerobic and anaerobic cultures were compared. However, in spite of the presence of functional ToxT, ctxAB expression was drastically reduced, and practically no CT was detected in cells grown under anaerobic conditions. In a V. cholerae hns mutant, however, high levels of ctxAB expression occurred even under anaerobic conditions. Also, deletion of the H-NS binding site from the ctxAB promoter eliminated anaerobic repression of ctxAB expression. These results suggest that H-NS directly represses ctxAB expression under anaerobic growth conditions. It has been reported that in the first stage of infection of infant mice by V. cholerae, tcpA is expressed but ctxAB expression is shut off (S. H. Lee, D. L. Hava, M. K. Waldor, and A. Camilli, Cell 99: 625-634, 1999). This pattern is similar to the pattern in anaerobic cultures of V. cholerae. Under all other in vitro conditions, ctxAB and tcpA are known to be coordinately expressed.
在霍乱弧菌中，跨膜DNA结合蛋白ToxR和TcpP会响应特定环境信号激活调控基因toxT的表达。由此产生的ToxT水平升高会导致包括霍乱毒素（CT）和毒素协同调节菌毛（TCP）在内的一部分毒力因子的产量协同增加。研究了厌氧环境对霍乱弧菌毒力调控级联反应表达的影响。在厌氧条件下生长的霍乱弧菌中，主要调控基因tcpP、toxR和toxT的表达与在有氧条件下生长的细胞中的表达相当，并且在比较需氧和厌氧培养物时，未检测到tcpA的ToxT依赖性表达有显著差异。然而，尽管存在功能性ToxT，但ctxAB的表达却大幅降低，并且在厌氧条件下生长的细胞中几乎检测不到CT。然而，在霍乱弧菌hns突变体中，即使在厌氧条件下也会出现高水平的ctxAB表达。此外，从ctxAB启动子中删除H-NS结合位点消除了ctxAB表达的厌氧抑制。这些结果表明，H-NS在厌氧生长条件下直接抑制ctxAB的表达。据报道，在霍乱弧菌感染幼鼠的第一阶段，tcpA表达但ctxAB表达关闭（S. H. Lee、D. L. Hava、M. K. Waldor和A. Camilli，《细胞》99: 625 - 634，1999）。这种模式与霍乱弧菌厌氧培养中的模式相似。在所有其他体外条件下，已知ctxAB和tcpA是协同表达的。
