Gene fitness landscape of group A streptococcus during necrotizing myositis
Gene fitness landscape of group A streptococcus during necrotizing myositis
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坏死性肌炎期间 A 族链球菌的基因适应性景观
DOI：
10.1101/432526
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发表时间：
2018
期刊：
影响因子：
--
通讯作者：
J. Musser
中科院分区：
文献类型：
--
作者：
Luchang Zhu;R. Olsen;Stephen B. Beres;J. Eraso;M. Saavedra;Samantha L. Kubiak;Concepcion C. Cantu;L. Jenkins;Amelia R. L. Charbonneau;A. Waller;J. Musser
坏死性筋膜炎和肌炎是具有高致死率的破坏性感染。A群链球菌（GAS）是这些感染的常见原因，但其分子发病机制尚不清楚。我们报告了一项使用血清型M1和M28菌株的全基因组分析，发现了与非人灵长类动物（NHP）（一种临床相关模型）坏死性肌炎有关的新型GAS基因。利用转座子定向插入位点测序（TraDIS），我们分别鉴定了126个和116个GAS基因，这些基因是M1和M28血清型生物体感染所需的。对于M1和M28菌株，超过25%的坏死性肌炎所需的GAS基因编码已知或假定的转运蛋白。在NHP肌炎中，13种GAS转运蛋白对M1和M28菌株的适应性都有贡献，包括氨基酸、碳水化合物和维生素的推定进口蛋白，以及毒素、群体感应肽和未表征分子的出口蛋白。编码5个转运蛋白的基因的靶向缺失证实了每个等基因突变株在NHPs中引起坏死性肌炎的能力显著受损。qRT-PCR分析显示，这5个基因在感染的NHP和人类骨骼肌中均有表达。这些转运体的某些底物结合脂蛋白，如Spy0271和Spy1728，先前被证明是表面暴露的，这表明我们的发现具有转化研究的意义。
Necrotizing fasciitis and myositis are devastating infections characterized by high mortality. Group A streptococcus (GAS) is a common cause of these infections, but the molecular pathogenesis is poorly understood. We report a genome-wide analysis using serotype M1 and M28 strains that identified novel GAS genes contributing to necrotizing myositis in nonhuman primates (NHP), a clinically relevant model. Using transposon directed insertion-site sequencing (TraDIS) we identified 126 and 116 GAS genes required for infection by serotype M1 and M28 organisms, respectively. For both M1 and M28 strains, more than 25% of the GAS genes required for necrotizing myositis encode known or putative transporters. Thirteen GAS transporters contributed to both M1 and M28 strain fitness in NHP myositis, including putative importers for amino acids, carbohydrates, and vitamins, and exporters for toxins, quorum sensing peptides, and uncharacterized molecules. Targeted deletion of genes encoding five transporters confirmed that each isogenic mutant strain was significantly impaired in causing necrotizing myositis in NHPs. qRT-PCR analysis showed that these five genes are expressed in infected NHP and human skeletal muscle. Certain substrate-binding lipoproteins of these transporters, such as Spy0271 and Spy1728, were previously documented to be surface-exposed, suggesting that our findings have translational research implications.
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影响因子：
6
作者：
Graham, MR;Virtaneva, K;Musser, JM
通讯作者：
Musser, JM
影响因子：
7
作者：
Langridge, Gemma C.;Phan, Minh-Duy;Turner, A. Keith
通讯作者：
Turner, A. Keith
影响因子：
20.3
作者：
Sun, Hongmin;Wang, Xixi;Ginsburg, David
通讯作者：
Ginsburg, David
DOI：
10.1073/pnas.88.19.8317
发表时间：
1991-10-01
影响因子：
11.1
作者：
WESSELS, MR;MOSES, AE;DICESARE, TJ
通讯作者：
DICESARE, TJ
影响因子：
2.6
作者：
PEREZCASAL, J;CAPARON, MG;SCOTT, JR
通讯作者：
SCOTT, JR