The classical lancefield antigen of group a Streptococcus is a virulence determinant with implications for vaccine design.
The classical lancefield antigen of group a Streptococcus is a virulence determinant with implications for vaccine design.
复制标题
DOI：
10.1016/j.chom.2014.05.009
复制
发表时间：
2014-06-11
影响因子：
30.3
通讯作者：
Nizet V
中科院分区：
文献类型：
--
作者：
van Sorge NM;Cole JN;Kuipers K;Henningham A;Aziz RK;Kasirer-Friede A;Lin L;Berends ETM;Davies MR;Dougan G;Zhang F;Dahesh S;Shaw L;Gin J;Cunningham M;Merriman JA;Hütter J;Lepenies B;Rooijakkers SHM;Malley R;Walker MJ;Shattil SJ;Schlievert PM;Choudhury B;Nizet V
A组链球菌（GAS）是人类感染相关死亡的主要原因。所有GAS血清型表达兰斯菲尔德A组碳水化合物（GAC），其包含具有免疫显性N-乙酰葡糖胺（GlcNAc）侧链的多聚鼠李糖主链，这是快速诊断测试的基础。没有生物学功能已归因于这种保守的抗原。在这里，我们确定和GAC生物合成基因，gacA-L的特点。糖基转移酶gacI的同基因突变体（其缺乏GlcNAc侧链加成）在两种感染模型中的毒力减弱，与对嗜中性粒细胞杀伤、血小板衍生的血清中的抗菌剂和凯萨林菌素抗菌肽LL-37的敏感性增加相关。抗体GAC缺乏GlcNAc侧链，只含有多聚鼠李糖促进调理吞噬杀死多种GAS血清型和保护系统GAS攻击后被动免疫。因此，兰斯菲尔德抗原在GAS发病机制中起着功能性作用，对它的理解对疫苗的开发具有重要意义。
Group A Streptococcus (GAS) is a leading cause of infection-related mortality in humans. All GAS serotypes express the Lancefield group A carbohydrate (GAC), comprising a polyrhamnose backbone with an immunodominant N-acetylglucosamine (GlcNAc) side chain, which is the basis of rapid diagnostic tests. No biological function has been attributed to this conserved antigen. Here we identify and characterize the GAC biosynthesis genes,gacA-L. An isogenic mutant of the glycosyltransferase gacI, which is defective for GlcNAcside chain addition, is attenuated for virulence in two infection models, in association with increased sensitivity to neutrophil killing, platelet-derived antimicrobials in serum and the cathelicidin antimicrobial peptide LL-37. Antibodies to GAC lacking the GlcNAc side chain and containing only polyrhamnose promoted opsonophagocytic killing of multiple GAS serotypes and protected against systemic GAS challenge after passive immunization. Thus, the Lancefield antigen plays a functional role in GAS pathogenesis and its understanding has implications for vaccine development.
登录
查看更多内容
影响因子：
3.1
作者：
Kansal, RG;McGeer, A;Kotb, M
通讯作者：
Kotb, M
影响因子：
5.5
作者：
Kabanova, Anna;Margarit, Immaculada;Costantino, Paolo
通讯作者：
Costantino, Paolo
影响因子：
15.9
作者：
Galvin, JE;Hemric, ME;Cunningham, MW
通讯作者：
Cunningham, MW
影响因子：
12.8
作者：
Faé, KC;Oshiro, SE;Guilherme, L
通讯作者：
Guilherme, L
影响因子：
11.8
作者：
Bisno, AL;Rubin, FA;Dale, JB
通讯作者：
Dale, JB