A Genital Infection-Attenuated Chlamydia muridarum Mutant Infects the Gastrointestinal Tract and Protects against Genital Tract Challenge.
A Genital Infection-Attenuated Chlamydia muridarum Mutant Infects the Gastrointestinal Tract and Protects against Genital Tract Challenge.
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DOI：
10.1128/mbio.02770-20
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发表时间：
2020-11-03
期刊：
影响因子：
6.4
通讯作者：
Morrison RP
中科院分区：
文献类型：
--
作者：
Morrison SG;Giebel AM;Toh E;Banerjee A;Nelson DE;Morrison RP
衣原体是美国最常见的性传播细菌感染。大多数衣原体生殖器感染解决没有严重的后果;然而，未经治疗的妇女感染可导致盆腔炎和不孕症。抗生素在治疗衣原体方面非常有效，但大多数男性和女性生殖器感染都没有症状，无法诊断。因此，迫切需要有效的疫苗。在这项工作中，我们表明，突变衣原体菌株，生殖器感染的毒力大大降低，殖民胃肠道，并产生强大的免疫生殖器的挑战与完全致命的野生型衣原体。这些结果是了解衣原体毒力的重要进展，并提供了令人信服的证据，安全有效的减毒衣原体活疫苗可能是可行的。衣原体属物种感染多个解剖部位的粘膜上皮细胞，包括结膜、肺、胃肠道（GI）和泌尿生殖道。我们和其他人先前已经确定衣原体的胃肠道嗜性是由不同的染色体和质粒因子介导的。在这项研究中，我们描述了一种生殖器感染减毒鼠衣原体突变体（GIAM-1），是深刻的和具体的衰减在小鼠生殖道。GIAM-1感染小鼠胃肠道类似于野生型（WT）鼠衣原体，但没有生产性感染雌性小鼠的下生殖道，上升感染上生殖道，或引起输卵管积水。然而，GI感染GIAM-1的小鼠引起了跨粘膜免疫应答，保护其免受随后的WT小鼠衣原体生殖器攻击。总的来说，我们的研究结果表明，衣原体突变体是深刻减毒的特定器官组织可以得到证明，减毒活疫苗株感染胃肠道，但不引起生殖道疾病，可用于防止衣原体生殖道感染和疾病。
Chlamydia is the most common sexually transmitted bacterial infection in the United States. Most chlamydia genital infections resolve without serious consequences; however, untreated infection in women can cause pelvic inflammatory disease and infertility. Antibiotics are very effective in treating chlamydia, but most genital infections in both men and women are asymptomatic and go undiagnosed. Therefore, there is a critical need for an effective vaccine. In this work, we show that a mutant chlamydia strain, having substantially reduced virulence for genital infection, colonizes the gastrointestinal tract and produces robust immunity to genital challenge with fully virulent wild-type chlamydia. These results are an important advance in understanding chlamydial virulence and provide compelling evidence that safe and effective live-attenuated chlamydia vaccines may be feasible. Chlamydia spp. productively infect mucosal epithelial cells of multiple anatomical sites, including the conjunctiva, lungs, gastrointestinal (GI) tract, and urogenital tract. We, and others, previously established that chlamydial GI tropism is mediated by distinct chromosomal and plasmid factors. In this study, we describe a genital infection-attenuated Chlamydia muridarum mutant (GIAM-1) that is profoundly and specifically attenuated in the murine genital tract. GIAM-1 infected the murine GI tract similarly to wild-type (WT) Chlamydia muridarum but did not productively infect the lower genital tract of female mice, ascend to infect the upper genital tract, or cause hydrosalpinx. However, GI infection of mice with GIAM-1 elicited a transmucosal immune response that protected against subsequent genital challenge with WT Chlamydia muridarum. Collectively, our results demonstrate that chlamydia mutants that are profoundly attenuated for specific organ tissues can be derived and demonstrate that live-attenuated vaccine strains that infect the GI tract, but do not elicit genital tract disease, could be used to protect against chlamydia genital tract infection and disease.