Vibrio cholerae virulence regulator-coordinated evasion of host immunity
Vibrio cholerae virulence regulator-coordinated evasion of host immunity
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DOI：
10.1073/pnas.0604650103
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发表时间：
2006-09-26
影响因子：
11.1
通讯作者：
Zhu, Jun
中科院分区：
文献类型：
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作者：
Hsiao, Ansel;Liu, Zhi;Zhu, Jun
为了成功地繁殖和引起疾病，病原性细菌必须响应于宿主免疫系统施加的压力来调节它们的转录活性，包括分泌的免疫球蛋白，如分泌型伊加（S-IgA），其可以结合和凝集细菌。在这里，我们提出了一个以前未描述的流式细胞术为基础的筛选方法，以确定在体外表达的细菌基因和霍乱弧菌，一种水生革兰氏阴性菌负责严重的霍乱弧菌感染过程中抑制。我们确定了一个IV型甘露糖敏感血凝素（MSHA）菌毛，在体内抑制特异性。我们发现，在S-IgA存在的情况下，未能关闭MSHA生物合成的细菌无法在幼鼠的肠道中定植。我们还发现，霍乱弧菌结合S-IgA的MSHA-透明和甘露糖敏感的方式和S-IgA的结合阻止细菌穿透粘液屏障和附着到上皮细胞的表面。霍乱弧菌通过下调表面粘附素来逃避S-IgA的非抗原特异性结合的能力代表了病原菌中先前未描述的免疫逃避机制。此外，我们发现MSHA的抑制是由关键的毒力转录因子ToxT介导的，表明霍乱弧菌能够协调毒力基因激活和抑制，以逃避宿主防御并成功地定殖肠道。
To successfully propagate and cause disease, pathogenic bacteria must modulate their transcriptional activities in response to pressures exerted by the host immune system, including secreted immunoglobulins such as secretory IgA (S-IgA), which can bind and agglutinate bacteria. Here, we present a previously undescribed flow cytometry-based screening method to identify bacterial genes expressed in vitro and repressed during infections of Vibrio cholerae, an aquatic Gram-negative bacterium responsible for the severe diarrheal disease cholera. We identified a type IV manno-sesensitive hemagglutinin (MSHA) pilus that is repressed specifically in vivo. We showed that bacteria that failed to turn off MSHA biosynthesis were unable to colonize the intestines of infant mice in the presence of S-IgA. We also found that V. cholerae bound S-IgA in an MSHA-clepenclent and mannose-sensitive fashion and that binding of S-IgA prevented bacteria from penetrating mucus barriers and attaching to the surface of epithelial cells. The ability of V. cholerae to evade the non-antigen-specific binding of S-IgA by down-regulating a surface adhesin represents a previously undescribed mechanism of immune evasion in pathogenic bacteria. In addition, we found that repression of MSHA was mediated by the key virulence transcription factor ToxT, indicating that V. cholerae is able to coordinate both virulence gene activation and repression to evade host defenses and successfully colonize intestines.