Reciprocal, temporal expression of SpeA and SpeB by invasive M1T1 group a streptococcal isolates in vivo
Reciprocal, temporal expression of SpeA and SpeB by invasive M1T1 group a streptococcal isolates in vivo
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DOI：
10.1128/iai.69.8.4988-4995.2001
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发表时间：
2001-08-01
影响因子：
3.1
通讯作者：
Kotb, M
中科院分区：
文献类型：
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作者：
Kazmi, SU;Kansal, R;Kotb, M
链球菌致热原外毒素（Spes）在侵袭性A组链球菌（GAS）感染的发病机制中起着重要作用。大多数最近的侵袭性GAS感染是由MIT 1菌株引起的，该菌株携带几种链球菌超抗原的基因，包括speA，speB，speF，spec和smeZ。然而，已经发现克隆M1分离株之间Spe蛋白表达的相当大的变化，并且许多speA阳性M1菌株在体外不产生可检测量的SpeA。本研究旨在验证speA基因表达可以在体内诱导的假设。一个小鼠感染室模型，允许连续采样的GAS分离株在不同的时间点postinfection的开发和用于监测体内的Spe生产的动力学。将微孔Teflon扩散室皮下植入BALB/c小鼠中，3周后，孔被结缔组织和无菌流体密封，所述无菌流体含有在感染室内积聚的白色血细胞浸润物。代表性的克隆MIT 1分离株表达没有检测到SpeA接种到植入的腔室中，并在连续几天感染后分析了SpeA在抽吸的腔室液体等分试样中的表达。SpeA的表达检测室流体中早在感染后3至5天，在大多数动物中，与一个显着增加的表达在第7天在所有感染的小鼠。从该室中回收并在体外生长的分离株即使在体外传代21次后仍继续产生SpeA，表明SpeA基因的稳定开关。在体内观察到SpeA表达的上调和SpeB表达的下调之间的时间关系。这些数据表明，在体内宿主和/或环境信号诱导speA基因的表达和抑制speB基因的表达。这强调了宿主-病原体相互作用在体内调节链球菌毒力因子表达中的作用。这里所描述的模型应该有助于这些研究。
The streptococcal pyrogenic exotoxins (Spes) play a central role in the pathogenesis of invasive group A streptococcal (GAS) infections. The majority of recent invasive GAS infections have been caused by an MIT1 strain that harbors the genes for several streptococcal superantigens, including speA, speB, speF, spec, and smeZ. However, considerable variation in the expression of Spe proteins among clonal M1 isolates has been found, and many of the speA-positive Ml strains do not produce detectable amounts of SpeA in vitro. This study was designed to test the hypothesis that speA gene expression can be induced in vivo. A mouse infection chamber model that allows sequential sampling of GAS isolates at various time points postinfection was developed and used to monitor the kinetics of Spe production in vivo. Micropore Teflon diffusion chambers were implanted subcutaneously in BALB/c mice, and after 3 weeks the pores became sealed with connective tissue and sterile fluid containing a white blood cell infiltrate accumulated inside the infection chambers. Representative clonal MIT1 isolates expressing no detectable SpeA were inoculated into the implanted chambers, and the expression of SpeA in the aspirated aliquots of the chamber fluid was analyzed on successive days postinfection. Expression of SpeA was detected in the chamber fluid as early as days 3 to 5 postinfection in most animals, with a significant increase in expression by day 7 in all infected mice. Isolates recovered from the chamber and grown in vitro continued to produce SpeA even after 21 passages in vitro, suggesting stable switch on of the speA gene. A temporal relation between the upregulation of SpeA expression and the downregulation of SpeB expression was observed in vivo. These data suggest that in vivo host and/or environmental signals induced speA gene expression and suppressed speB gene expression. This underscores the role of the host-pathogen interaction in regulating the expression of streptococcal virulence factors in vivo. The model described here should facilitate such studies.