Sun Qiangzheng, Knirel Yuriy A, Wang Jianping, Luo Xia, Senchenkova Sofya N, Lan Ruiting, Shashkov Alexander S, Xu Jianguo
State Key Laboratory for Infectious Disease Prevention and Control, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, National Institute for Communicable Disease Control and Prevention, China CDC, Changping, Beijing, China
N. D. Zelinsky Institute of Organic Chemistry, Russian Academy of Sciences, Moscow, Russian Federation.
J Bacteriol. 2014 Oct;196(20):3656-66. doi: 10.1128/JB.02009-14. Epub 2014 Aug 11.
Shigella flexneri O-antigen is an important and highly variable cell component presented on the outer leaflet of the outer membrane. Most Shigella flexneri bacteria share an O-antigen backbone composed of →2)-α-L-Rhap(III)-(1→2)-α-L-Rhap(II)-(1→3)-α-L-Rhap(I)-(1→3)-β-D-GlcpNAc-(1→ repeats, which can be modified by adding various chemical groups to different sugars, giving rise to diverse O-antigen structures and, correspondingly, to various serotypes. The known modifications include glucosylation on various sugar residues, O-acetylation on Rha(I) or/and Rha(III), and phosphorylation with phosphoethanolamine on Rha(II) or/and Rha(III). Recently, a new O-antigen modification, namely, O-acetylation at position 6 of N-acetylglucosamine (GlcNAc), has been identified in S. flexneri serotypes 2a, 3a, Y, and Yv. In this study, the genetic basis of the 6-O-acetylation of GlcNAc in S. flexneri was elucidated. An O-acyltransferase gene designated oacD was found to be responsible for this modification. The oacD gene is carried on serotype-converting bacteriophage SfII, which is integrated into the host chromosome by lysogeny to form a prophage responsible for the evolvement of serotype 2 of S. flexneri. The OacD-mediated 6-O-acetylation also occurs in some other S. flexneri serotypes that carry a cryptic SfII prophage with a dysfunctional gtr locus for type II glucosylation. The 6-O-acetylation on GlcNAc confers to the host a novel O-antigen epitope, provisionally named O-factor 10. These findings enhance our understanding of the mechanisms of the O-antigen variation and enable further studies to understand the contribution of the O-acetylation to the antigenicity and pathogenicity of S. flexneri.
福氏志贺菌O抗原是一种重要且高度可变的细胞成分，位于外膜的外小叶上。大多数福氏志贺菌具有由→2)-α-L-鼠李糖（III）-(1→2)-α-L-鼠李糖（II）-(1→3)-α-L-鼠李糖（I）-(1→3)-β-D-氨基葡萄糖-(1→重复序列组成的O抗原主链，该主链可通过向不同糖类添加各种化学基团进行修饰，从而产生多样的O抗原结构，并相应地形成各种血清型。已知的修饰包括在各种糖残基上进行糖基化、在鼠李糖（I）或/和鼠李糖（III）上进行O-乙酰化，以及在鼠李糖（II）或/和鼠李糖（III）上用磷酸乙醇胺进行磷酸化。最近，在福氏志贺菌血清型2a、3a、Y和Yv中发现了一种新的O抗原修饰，即N-乙酰葡萄糖胺（GlcNAc）第6位的O-乙酰化。在本研究中，阐明了福氏志贺菌中GlcNAc 6-O-乙酰化的遗传基础。发现一个名为oacD的O-酰基转移酶基因负责这种修饰。oacD基因位于血清型转换噬菌体SfII上，该噬菌体通过溶原作用整合到宿主染色体中，形成一个负责福氏志贺菌血清型2进化的前噬菌体。OacD介导的6-O-乙酰化也发生在其他一些福氏志贺菌血清型中，这些血清型携带一个隐性SfII前噬菌体，其II型糖基化的gtr位点功能失调。GlcNAc上的6-O-乙酰化为宿主赋予了一种新的O抗原表位，暂命名为O因子10。这些发现增进了我们对O抗原变异机制的理解，并使进一步研究能够了解O-乙酰化对福氏志贺菌抗原性和致病性的贡献。
