Genome sequence of a Lancefield group C Streptococcus zooepidemicus strain causing epidemic nephritis: new information about an old disease.
Genome sequence of a Lancefield group C Streptococcus zooepidemicus strain causing epidemic nephritis: new information about an old disease.
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DOI：
10.1371/journal.pone.0003026
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发表时间：
2008-08-21
期刊：
影响因子：
3.7
通讯作者：
Musser JM
中科院分区：
文献类型：
--
作者：
Beres SB;Sesso R;Pinto SW;Hoe NP;Porcella SF;Deleo FR;Musser JM
由于人为错误或自然原因引起的疾病暴发可以提供独特的机会，以获得有关宿主-病原体相互作用的新信息，并为发病机制研究提供新的线索。链球菌后肾小球肾炎（PSGN）是致病性链球菌感染的后遗症，是世界范围内可预防肾脏疾病的常见原因。虽然PSGN通常在感染A群链球菌后发生，但兰斯菲尔德C群和G群细菌也可能是原因。尽管经过数十年的研究，PSGN的分子发病机制尚不清楚。作为获得PSGN发病机制新信息的第一步，我们对马链球菌亚种的基因组进行了测序。动物流行病菌株MGCS10565，一种在巴西引起非常大且异常严重的肾炎流行的C组生物。基因组是2,024,171 bp的环状染色体。基因组与遗传相关的A群链球菌共享广泛的基因内容，包括许多毒力因子，但出人意料地缺乏前噬菌体。基因组包含许多明显的外源基因，散布在染色体周围，与自然能力所需的完整基因阵列的存在相一致。一个非常大的基因家族编码分泌的细胞外胶原样蛋白与多个整合素结合基序。与speB相关基因的缺失排除了长期以来认为链球菌热原外毒素B或与之反应的抗体单独引起PSGN的观点。许多先前与GAS PSGN相关的蛋白质，如链激酶，要么在菌株MGCS10565中高度分化，要么在这些物种之间的相关性并不比其他通常不引起PSGN的链球菌中存在的同源物更密切。我们的分析为重新评估APSGN发病机制的分子事件提供了一个比较基因组学框架。
Outbreaks of disease attributable to human error or natural causes can provide unique opportunities to gain new information about host-pathogen interactions and new leads for pathogenesis research. Poststreptococcal glomerulonephritis (PSGN), a sequela of infection with pathogenic streptococci, is a common cause of preventable kidney disease worldwide. Although PSGN usually occurs after infection with group A streptococci, organisms of Lancefield group C and G also can be responsible. Despite decades of study, the molecular pathogenesis of PSGN is poorly understood. As a first step toward gaining new information about PSGN pathogenesis, we sequenced the genome of Streptococcus equi subsp. zooepidemicus strain MGCS10565, a group C organism that caused a very large and unusually severe epidemic of nephritis in Brazil. The genome is a circular chromosome of 2,024,171 bp. The genome shares extensive gene content, including many virulence factors, with genetically related group A streptococci, but unexpectedly lacks prophages. The genome contains many apparently foreign genes interspersed around the chromosome, consistent with the presence of a full array of genes required for natural competence. An inordinately large family of genes encodes secreted extracellular collagen-like proteins with multiple integrin-binding motifs. The absence of a gene related to speB rules out the long-held belief that streptococcal pyrogenic exotoxin B or antibodies reacting with it singularly cause PSGN. Many proteins previously implicated in GAS PSGN, such as streptokinase, are either highly divergent in strain MGCS10565 or are not more closely related between these species than to orthologs present in other streptococci that do not commonly cause PSGN. Our analysis provides a comparative genomics framework for renewed appraisal of molecular events underlying APSGN pathogenesis.