Capsule loss or death: The position of mutations among capsule genes sways the destiny of Streptococcus suis

Capsule loss or death: The position of mutations among capsule genes sways the destiny of Streptococcus suis
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DOI:
10.1111/1574-6968.12428
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发表时间:
2014-05-01
影响因子:
2.1
通讯作者:
Sekizaki, Tsutomu
Sekizaki, Tsutomu
中科院分区:
生物学4区
文献类型:
--
作者:
Lakkitjaroen, Nattakan;Takamatsu, Daisuke;Sekizaki, Tsutomu

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猪链球菌(Streptococcus suis)是一种新出现的人畜共患病原体,可引起猪和人类的多种疾病。大多数临床分离的猪链球菌都具有一组荚膜多糖合成基因(capsular polysaccharide synthesis,cps),并表现为表达荚膜多糖(capsular polysaccharides,CP)。虽然CP被认为是一个重要的毒力因子,但我们以前的研究表明,许多猪链球菌心内膜炎分离株的CP丢失,其中一些未封装的分离株在cps基因簇中存在较大的插入或缺失。我们进一步研究了25个没有明显遗传改变的心内膜炎分离株,以阐明脱囊机制,发现两个糖基转移酶基因(cps 2 E和cps 2F)的单核苷酸取代和移码突变是导致包膜丢失的主要原因。此外,参与侧链形成(cps 2 J和cps 2N),聚合酶(cps 2 I)和翻转酶(cps 2 O)的基因突变似乎是致命的;然而,这些致命的影响被缓解的cps 2 EF区域的突变。由于最近有人认为单个细胞的脱囊甚至死亡有利于感染的发病机制,本研究的结果为理解猪链球菌感染过程中cps突变的生物学意义提供了进一步的见解。
Streptococcus suis, an emerging zoonotic pathogen, is responsible for various diseases in swine and humans. Most S.suis strains from clinical cases possess a group of capsular polysaccharide synthesis (cps) genes and phenotypically express capsular polysaccharides (CPs). Although CPs are considered to be an important virulence factor, our previous study showed that many S.suis isolates from porcine endocarditis lost their CPs, and some of these unencapsulated isolates had large insertions or deletions in the cps gene clusters. We further investigated 25 endocarditis isolates with no obvious genetic alterations to elucidate the unencapsulation mechanisms and found that a single-nucleotide substitution and frameshift mutation in two glycosyltransferase genes (cps2E and cps2F) were the main causes of the capsule loss. Moreover, mutations in the genes involved in side-chain formation (cps2J and cps2N), polymerase (cps2I), and flippase (cps2O) appeared to be lethal; however, these lethal effects were relieved by mutations in the cps2EF region. As unencapsulation and even the death of individual cells have recently been suggested to be beneficial to the pathogenesis of infections, the results of the present study provide a further insight into understanding the biological significance of cps mutations during the course of S.suis infections.