Genome sequence of a serotype M3 strain of group A Streptococcus:: Phage-encoded toxins, the high-virulence phenotype, and clone emergence
Genome sequence of a serotype M3 strain of group A Streptococcus:: Phage-encoded toxins, the high-virulence phenotype, and clone emergence
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DOI：
10.1073/pnas.152298499
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发表时间：
2002-07-23
影响因子：
11.1
通讯作者：
Musser, JM
中科院分区：
文献类型：
--
作者：
Beres, SB;Sylva, GL;Musser, JM
基因组序列可用于许多细菌菌株，但在使用这些数据来了解病原体出现的分子基础和菌株毒力差异方面进展甚微。A组链球菌（GAS）的血清型M3菌株是严重侵袭性感染的常见原因，具有异常高的发病率和死亡率。为了深入了解这种高毒力表型的分子基础，我们对MGAS 315菌株的基因组进行了测序，MGAS 315是一种从链球菌中毒性休克综合征患者中分离出来的微生物。基因组全长1，900，521 bp，与血清型M1和M18株基因组共有约1.7 Mb的遗传物质。相对于测序的M1和M18菌株，噬菌体样元件占基因含量变异的绝大多数。突变产生了具有以前未表征的毒力因子基因阵列的嵌合病毒和菌株。菌株MGAS 315具有编码可能有助于致病的蛋白质的噬菌体基因，例如链球菌致热外毒素A（SpeA）和SpeK、链球菌超抗原（SSA）和先前未表征的磷脂酶A（2）（命名为Sla）。受感染的人具有抗SpeK、抗SSA和抗Sla抗体，表明这些GAS蛋白是在体内产生的。SpeK和SSA对家兔有致热原性和毒性。具有噬菌体编码的speK和sla基因的血清型M3菌株的频率在20世纪后期急剧增加，与由M3生物体引起的侵袭性疾病的增加相称。两者合计，结果表明，噬菌体介导的重组发挥了关键作用，出现了一个新的，异常毒力克隆的血清型M3 GAS。
Genome sequences are available for many bacterial strains, but there has been little progress in using these data to understand the molecular basis of pathogen emergence and differences in strain virulence. Serotype M3 strains of group A Streptococcus (GAS) are a common cause of severe invasive infections with unusually high rates of morbidity and mortality. To gain insight into the molecular basis of this high-virulence phenotype, we sequenced the genome of strain MGAS315, an organism isolated from a patient with streptococcal toxic shock syndrome. The genome is composed of 1,900,521 bp, and it shares approximate to1.7 Mb of related genetic material with genomes of serotype M1 and M18 strains. Phage-like elements account for the great majority of variation in gene content relative to the sequenced M1 and M18 strains. Recombination produces chimeric phages and strains with previously uncharacterized arrays of virulence factor genes. Strain MGAS315 has phage genes that encode proteins likely to contribute to pathogenesis, such as streptococcal pyrogenic exotoxin A (SpeA) and SpeK, streptococcal superantigen (SSA), and a previously uncharacterized phospholipase A(2) (designated Sla). Infected humans had anti-SpeK, -SSA, and -Sla antibodies, indicating that these GAS proteins are made in vivo. SpeK and SSA were pyrogenic and toxic for rabbits. Serotype M3 strains with the phage-encoded speK and sla genes increased dramatically in frequency late in the 20th century, commensurate with the rise in invasive disease caused by M3 organisms. Taken together, the results show that phage-mediated recombination has played a critical role in the emergence of a new, unusually virulent clone of serotype M3 GAS.