Department of Animal, Veterinary and Food Science, University of Idaho, Moscow, Idaho, USA.
Division of Vector-Borne Diseases, Centers for Disease Control and Prevention, Fort Collins, Colorado, USA.
Appl Environ Microbiol. 2023 Feb 28;89(2):e0124422. doi: 10.1128/aem.01244-22. Epub 2023 Feb 6.
Ail confers serum resistance in humans and is a critical virulence factor of Y. pestis, the causative agent of plague. Here, the contribution of Ail for Y. pestis survival in the flea vector was examined. Rat or human but not mouse sera were bactericidal against a Y. pestis Δ mutant at 28°C . Complement components deposited rapidly on the Y. pestis surface as measured by immunofluorescent microscopy. Ail reduced the amount of active C3b on the Y. pestis surface. Human sera retained bactericidal activity against a Y. pestis Δ mutant in the presence of mouse sera. However, in the flea vector, the serum protective properties of Ail were not required. Flea colonization studies using murine sera and Y. pestis KIM6 wild type, a Δ mutant, and the Δ control showed no differences in bacterial prevalence or numbers during the early stage of flea colonization. Similarly, flea studies with human blood showed Ail was not required for serum resistance. Finally, a variant of Ail (Ail) from a human serum-sensitive Y. pestis subsp. microtus bv. Caucasica 1146 conferred resistance to human complement when expressed in the Y. pestis KIM6 Δ mutant. This indicated that Ail activity was somehow blocked, most likely by lipooligosaccharide, in this serum sensitive strain. This work contributes to our understanding of how highly virulent Y. pestis evolved from its innocuous enteric predecessor. Among identified virulence factors is the attachment invasion locus protein, Ail, that is required to protect Y. pestis from serum complement in all mammals tested except mice. Murine sera is not bactericidal. In this study, we asked, is bactericidal sera from humans active in Y. pestis colonized fleas? We found it was not. The importance of this observation is that it identifies a protective niche for the growth of serum sensitive and nonsensitive Y. pestis strains.
Ail 赋予人类血清抗性，是鼠疫耶尔森氏菌（鼠疫的病原体）的关键毒力因子。在这里，研究了 Ail 对鼠疫耶尔森氏菌在跳蚤载体中的生存的贡献。在 28°C 下，大鼠或人但不是小鼠的血清对 Y. pestisΔ突变体具有杀菌作用。如免疫荧光显微镜测量所示，补体成分迅速沉积在 Y. pestis 表面。Ail 减少了 Y. pestis 表面上活性 C3b 的量。在存在小鼠血清的情况下，人血清保留了对 Y. pestisΔ突变体的杀菌活性。然而，在跳蚤载体中，Ail 的血清保护特性不是必需的。使用鼠血清和 Y. pestis KIM6 野生型、Δ突变体和Δ对照进行跳蚤定植研究表明，在跳蚤定植的早期阶段，细菌的流行率或数量没有差异。同样，用人血进行的跳蚤研究表明，Ail 对于血清抗性不是必需的。最后，来自人类血清敏感的鼠疫耶尔森氏菌亚种。高加索 1146 的 Ail 变体（Ail）在 Y. pestis KIM6Δ突变体中表达时赋予了对人补体的抗性。这表明在这种血清敏感株中，Ail 活性被某种方式阻断，很可能是被脂寡糖阻断。这项工作有助于我们了解高度致命的鼠疫耶尔森氏菌是如何从其无害的肠型前体进化而来的。已鉴定的毒力因子之一是附着入侵基因座蛋白 Ail，它需要保护 Y. pestis 免受所有测试的哺乳动物（除了小鼠）血清补体的杀伤。鼠血清没有杀菌作用。在这项研究中，我们想知道，来自人类的杀菌血清在被 Y. pestis 定植的跳蚤中是否活跃？我们发现并非如此。这一观察结果的重要性在于，它确定了血清敏感和非敏感 Y. pestis 菌株生长的保护生态位。
