化脓链球菌rocA 基因的一个自然发生的点突变赋予了其高度毒力表型。

A naturally occurring point mutation in the rocA gene of Streptococcus pyogenes confers the highly virulent phenotype.

机构信息

Department of Infection Control and Immunology, Omura Satoshi Memorial Institute and Graduate School of Infection Control Sciences, Kitasato University, 5-9-1 Shirokane, Minato-ku, Tokyo 108-8641, Japan.

出版信息

J Infect Chemother. 2021 Apr;27(4):578-584. doi: 10.1016/j.jiac.2020.11.009. Epub 2020 Dec 11.

DOI:10.1016/j.jiac.2020.11.009

PMID:33309630

Abstract

INTRODUCTION

Mucoid (MTB313) and nonmucoid (MTB314) strains of group A streptococcus (GAS) emm (antiphagocytic M protein) type 1 were simultaneously isolated from a single patient suffering from streptococcal meningitis. In a CD46-expressing transgenic (CD46 Tg) mouse model of subcutaneous infection into both hind footpads with MTB313 or MTB314, MTB313 showed considerably higher virulence than MTB314.

METHODS

The comparative genomic analysis based on the whole-genome sequencing revealed that MTB313 possessed an amber codon within rocA (sensory transduction protein kinase), but MTB314 did not carry this stop codon. Thereafter, MAT101 was generated from MTB313 by introducing pRocA, which contained the full-length rocA from MTB314, into the cloning plasmid pLZ12-Km2. MAT100 was also generated by introducing pLZ12-Km2 into MTB313.

RESULTS

Although MTB313 and MAT100 showed large quantities of cell-associated hyaluronic acid (HA) in the culture pellets, MTB314 and MAT101 showed small quantities of HA production. Finally, higher mortalities were observed in the MTB313- or MAT100-infected CD46 Tg mice than the MTB314- or MAT101-infected CD46 Tg mice.

CONCLUSIONS

These data indicate the possibility that a spontaneous point mutation in the rocA gene led to the highly virulent phenotype of M1 GAS.

摘要

简介

从患有链球菌性脑膜炎的单一患者中同时分离出 A 组链球菌（GAS）emm（抗吞噬 M 蛋白）型 1 的粘质（MTB313）和非粘质（MTB314）菌株。在 CD46 表达的转基因（CD46Tg）小鼠模型中，通过将 MTB313 或 MTB314 同时接种到两个后脚掌的皮下感染中，MTB313 显示出比 MTB314 高得多的毒力。

方法

基于全基因组测序的比较基因组分析表明，MTB313 在 rocA（感觉转导蛋白激酶）中具有琥珀色密码子，但 MTB314 没有携带此终止密码子。此后，通过将包含来自 MTB314 的全长 rocA 的 pRocA 引入克隆质粒 pLZ12-Km2 中，从 MTB313 中生成了 MAT101。MAT100 也是通过将 pLZ12-Km2 引入 MTB313 而产生的。