Slipped-strand mispairing within a polycytidine tract in transcriptional regulator mga leads to M protein phase variation and Mga length polymorphism in Group A Streptococcus.
Slipped-strand mispairing within a polycytidine tract in transcriptional regulator mga leads to M protein phase variation and Mga length polymorphism in Group A Streptococcus.
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DOI：
10.3389/fmicb.2023.1212149
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发表时间：
2023
影响因子：
5.2
通讯作者：
中科院分区：
文献类型：
--
作者：
M蛋白是A组链球菌（Group A Streptococcus，GAS）的主要毒力因子，受多基因调控因子Mga的调控。M1 T1 GAS菌株的体外遗传操作或培养中经常发生的一种无法解释的现象是M蛋白产生的损失。本研究旨在阐明M蛋白生产损失的基础。大多数M蛋白阴性（M−）变异体在M1 mga基因的碱基1，571处开始的8个胞苷序列中有一个C缺失，称为c.1571C[8]。C缺失导致c.1571C[7] mga变体，其具有开放阅读移码并编码Mga-M蛋白融合蛋白。用含有野生型mga的质粒转化恢复了c.1571C[7] mga变体中M蛋白的产生。在小鼠皮下接种c.1571C[7] M蛋白阴性变体后，回收产生M蛋白（M+）的分离株。大多数恢复M蛋白生产的回收分离株已从c.1571C[7]恢复到c.1571C[8]区，一些M+分离株在c.1571C[7]区中丢失了另一个C，导致c.1571C[6]变体编码功能性Mga，与野生型Mga相比，其C末端具有13个额外的氨基酸残基。非功能性c.1571C[7]和功能性c.1571C[6]变体存在于NCBI基因组数据库中的M1、M12、M14和M23菌株中，M12 c.1574C[7] mga碱基1，657处的G至A无义突变导致功能性c.1574C[7]/1657 A mga变体，并且在临床M12分离株中常见。多胞苷序列中C重复序列的数量和碱基1，657的多态性导致临床分离株中Mga大小的多态性。这些发现表明mga的c.1574C[8]道内的滑动链错配作为控制多种GAS常见M类型中M蛋白产生相位变化的可逆开关。
The M protein, a major virulence factor of Group A Streptococcus (GAS), is regulated by the multigene regulator Mga. An unexplained phenomena frequently occurring with in vitro genetic manipulation or culturing of M1T1 GAS strains is the loss of M protein production. This study was aimed at elucidating the basis for the loss of M protein production. The majority of M protein-negative (M−) variants had one C deletion at a tract of 8 cytidines starting at base 1,571 of the M1 mga gene, which is designated as c.1571C[8]. The C deletion led to a c.1571C[7] mga variant that has an open reading frame shift and encodes a Mga-M protein fusion protein. Transformation with a plasmid containing wild-type mga restored the production of the M protein in the c.1571C[7] mga variant. Isolates producing M protein (M+) were recovered following growth of the c.1571C[7] M protein-negative variant subcutaneously in mice. The majority of the recovered isolates with reestablished M protein production had reverted back from c.1571C[7] to c.1571C[8] tract and some M+ isolates lost another C in the c.1571C[7] tract, leading to a c.1571C[6] variant that encodes a functional Mga with 13 extra amino acid residues at the C-terminus compared with wild-type Mga. The nonfunctional c.1571C[7] and functional c.1571C[6] variants are present in M1, M12, M14, and M23 strains in NCBI genome databases, and a G-to-A nonsense mutation at base 1,657 of M12 c.1574C[7] mga leads to a functional c.1574C[7]/1657A mga variant and is common in clinical M12 isolates. The numbers of the C repeats in this polycytidine tract and the polymorphism at base 1,657 lead to polymorphism in the size of Mga among clinical isolates. These findings demonstrate the slipped-strand mispairing within the c.1574C[8] tract of mga as a reversible switch controlling M protein production phase variation in multiple GAS common M types.
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影响因子：
3.6
作者：
Rasmussen, M;Björck, L
通讯作者：
Björck, L
DOI：
10.1007/978-0-387-73960-1_3
发表时间：
2008-01-01
期刊：
HOT TOPICS IN INFECTION AND IMMUNITY IN CHILDREN IV
影响因子：
--
作者：
Cunningham, Madeleine W.
通讯作者：
Cunningham, Madeleine W.
影响因子：
3.1
作者：
Lukomski, S;Nakashima, K;Musser, JM
通讯作者：
Musser, JM
影响因子：
0.8
作者：
Murase K;Nozawa T;Aikawa C;Nagao M;Ikebe T;Yoshida A;Kikuchi T;Nakagawa I
通讯作者：
Nakagawa I
DOI：
10.1073/pnas.152298499
发表时间：
2002-07-23
影响因子：
11.1
作者：
Beres, SB;Sylva, GL;Musser, JM
通讯作者：
Musser, JM