School of Biological Sciences, Department of Molecular and Biomedical Science, Research Centre for Infectious Diseases, University of Adelaide, Adelaide, Australia.
Department of Organic Chemistry, Arrhenius Laboratory, Stockholm University, Stockholm, Sweden.
J Bacteriol. 2020 Nov 19;202(24). doi: 10.1128/JB.00363-20.
is a major causative agent of bacillary dysentery in developing countries, where serotype 2a is the prevalent strain. To date, approximately 30 serotypes have been identified for , and the major contribution to the emergence of new serotypes is chemical modifications of the lipopolysaccharide (LPS) component O antigen (Oag). Glucosylation, O-acetylation, and phosphoethanolamine (PEtN) modifications increase the Oag diversity, providing benefits to LPS Oag acts as a primary receptor for bacteriophage Sf6, which infects only a limited range of serotypes (Y and X). It uses its tailspike protein (Sf6TSP) to establish initial interaction with LPS Oags that it then hydrolyzes. Currently, there is a lack of comprehensive study on the parent and serotype variant strains from the same genetic background and an understanding of the importance of LPS Oag O-acetylations. Therefore, a set of isogenic strains (based on 2457T [2a]) with deletions of different Oag modification genes (, , and ) that resemble different naturally occurring serotype Y and 2a strains was created. The impacts of these Oag modifications on sensitivity to Sf6 and the pathogenesis-related properties were then compared. We found that Sf6TSP can hydrolyze serotype 2a LPS Oag, identified that 3/4-O-acetylation is essential for resistance of serotype 2a strains to Sf6, and showed that serotype 2a strains have better invasion ability. Lastly, we revealed two new serotype conversions for , thereby contributing to understanding the evolution of this important human pathogen. The emergence of antibiotic-resistant strains and lack of efficient vaccines have made a priority organism for the World Health Organization (1). Therefore, bacteriophage therapy has received increasing attention as an alternative therapeutic approach. LPS Oag is the most variable part of LPS due to chemical modifications and is the target of bacteriophage Sf6 ( specific). We dissected the evolution of serotype Y to 2a, which revealed a new role for a gene acquired during serotype conversion and furthermore identified new specific forms of LPS receptor for Sf6. Collectively, these results unfold the importance of the acquisition of those Oag modification genes and further our understanding of the relationship between Sf6 and .
是发展中国家细菌性痢疾的主要病原体，其中血清型 2a 是主要流行株。迄今为止，已经鉴定出约 30 种血清型，而新血清型的出现主要归因于脂多糖（LPS）O 抗原（Oag）成分的化学修饰。糖基化、O-乙酰化和磷酸乙醇胺（PEtN）修饰增加了 Oag 的多样性，使 LPS Oag 作为噬菌体 Sf6 的主要受体发挥作用，噬菌体 Sf6 仅感染有限范围的血清型（Y 和 X）。它使用其尾刺蛋白（Sf6TSP）与 LPS Oag 建立初始相互作用，然后将其水解。目前，缺乏对来自同一遗传背景的亲代和血清型变异株的全面研究，也缺乏对 LPS Oag O-乙酰化重要性的认识。因此，一组基于 2457T（2a）的具有不同 Oag 修饰基因（、、和）缺失的同源基因菌株（类似于不同的天然存在的血清型 Y 和 2a 菌株）被创建。然后比较了这些 Oag 修饰对 Sf6 敏感性和发病相关特性的影响。我们发现 Sf6TSP 可以水解血清型 2a LPS Oag，鉴定出 3/4-O-乙酰化对于血清型 2a 菌株抵抗 Sf6 至关重要，并表明血清型 2a 菌株具有更好的侵袭能力。最后，我们揭示了 的两种新的血清型转换，从而有助于理解这种重要的人类病原体的进化。抗生素耐药菌株的出现和缺乏有效的疫苗使成为世界卫生组织（1）的优先研究对象。因此，噬菌体治疗作为一种替代治疗方法受到了越来越多的关注。由于化学修饰，LPS Oag 是 LPS 中最易变的部分，是噬菌体 Sf6 的靶标（特异性）。我们剖析了血清型 Y 向 2a 的进化，揭示了在血清型转换过程中获得的一个基因的新作用，并进一步确定了 Sf6 的新的 LPS 受体特异性形式。总之，这些结果揭示了获得这些 Oag 修饰基因的重要性，并进一步加深了我们对 Sf6 和之间关系的理解。
