Bacillus subtilis-Mediated Protection from Citrobacter rodentium-Associated Enteric Disease Requires espH and Functional Flagella
Bacillus subtilis-Mediated Protection from Citrobacter rodentium-Associated Enteric Disease Requires espH and Functional Flagella
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DOI：
10.1128/iai.05843-11
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发表时间：
2012-02-01
影响因子：
3.1
通讯作者：
Knight, Katherine L.
中科院分区：
文献类型：
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作者：
Jones, Sara E.;Knight, Katherine L.
共生菌限制了入侵病原体引起的疾病;然而，对有益微生物用于抑制发病机制的机制和基因知之甚少。附着和消失的小鼠病原体啮齿柠檬酸杆菌与肠上皮密切相关，感染导致急性结肠炎。C.啮齿动物是用来模拟人类病原体肠出血性大肠杆菌和肠致病性大肠杆菌。杆菌为了证实枯草芽孢杆菌（一种在哺乳动物肠道中发现的孢子形成细菌）可以减少C。啮齿类相关疾病，小鼠接受野生型B。枯草芽孢杆菌孢子感染，24 h后用致病性C.啮齿动物。通过确定结肠上皮增生、杯状细胞丢失、腹泻和病原体定植的程度来评估疾病。接受野生型B.枯草芽孢杆菌肠道感染前的保护免受疾病，即使C.啮齿动物定殖未被抑制。相比之下，espH和hag突变体，在胞外多糖和鞭毛生产缺陷，分别不能保护小鼠从C。啮齿动物相关疾病一个motAB突变体也不能保护小鼠免受疾病的侵害，这表明B。枯草杆菌介导的保护需要功能性鞭毛。通过扩展我们目前对细菌保护的机制知识，我们可以更好地利用有益微生物来预防致病菌引起的肠道疾病，最终减少人类疾病。我们的数据表明野生型B. subtilis减少了C.啮齿类感染通过一种机制，需要espH和功能鞭毛。
Commensals limit disease caused by invading pathogens; however, the mechanisms and genes utilized by beneficial microbes to inhibit pathogenesis are poorly understood. The attaching and effacing mouse pathogen Citrobacter rodentium associates intimately with the intestinal epithelium, and infections result in acute colitis. C. rodentium is used to model the human pathogens enterohemorrhagic Escherichia coli and enteropathogenic E. coli. To confirm that Bacillus subtilis, a spore-forming bacterium found in the gut of mammals, could reduce C. rodentium-associated disease, mice received wild-type B. subtilis spores and 24 h later were infected by oral gavage with pathogenic C. rodentium. Disease was assessed by determining the extent of colonic epithelial hyperplasia, goblet cell loss, diarrhea, and pathogen colonization. Mice that received wild-type B. subtilis prior to enteric infection were protected from disease even though C. rodentium colonization was not inhibited. In contrast, espH and hag mutants, defective in exopolysaccharides and flagellum production, respectively, did not protect mice from C. rodentium-associated disease. A motAB mutant also failed to protect mice from disease, suggesting that B. subtilis-mediated protection requires functional flagella. By expanding our current mechanistic knowledge of bacterial protection, we can better utilize beneficial microbes to prevent intestinal disease caused by pathogenic bacteria, ultimately reducing human disease. Our data demonstrate that wildtype B. subtilis reduced disease caused by C. rodentium infection through a mechanism that required espH and functional flagella.