Department of Oral and Molecular Microbiology, Osaka University Graduate School of Dentistry, Suita, Osaka, Japan
Department of Oral and Molecular Microbiology, Osaka University Graduate School of Dentistry, Suita, Osaka, Japan.
Appl Environ Microbiol. 2019 Oct 16;85(21). doi: 10.1128/AEM.01428-19. Print 2019 Nov 1.
is a major cause of necrotizing fasciitis, a life-threatening subcutaneous soft-tissue infection. At the host infection site, the local environment and interactions between the host and bacteria have effects on bacterial gene expression profiles, while the gene expression pattern of related to this disease remains unknown. In this study, we used a mouse model of necrotizing fasciitis and performed RNA-sequencing (RNA-seq) analysis of M1T1 strain 5448 by isolating total RNA from infected hind limbs obtained at 24, 48, and 96 h postinfection. RNA-seq analysis results identified 483 bacterial genes whose expression was consistently altered in the infected hindlimbs compared to their expression under conditions. Genes showing consistent enrichment during infection included 306 encoding molecules involved in virulence, carbohydrate utilization, amino acid metabolism, trace-metal transport, and the vacuolar ATPase transport system. Surprisingly, drastic upregulation of 3 genes, encoding streptolysin S precursor (), cysteine protease (), and secreted DNase (), was noted in the present mouse model (log fold change, >6.0, >9.4, and >7.1, respectively). Conversely, the number of consistently downregulated genes was 177, including those associated with the oxidative stress response and cell division. These results suggest that in necrotizing fasciitis, shows an altered metabolism, decreased cell proliferation, and upregulation of expression of major toxins. Our findings are considered to provide critical information for developing novel treatment strategies and vaccines for necrotizing fasciitis. Necrotizing fasciitis, a life-threatening subcutaneous soft-tissue infection, is principally caused by The inflammatory environment at the site of infection causes global gene expression changes for survival of the bacterium and pathogenesis. However, no known study regarding transcriptomic profiling of in cases of necrotizing fasciitis has been presented. We identified 483 bacterial genes whose expression was consistently altered during infection. Our results showed that infection induces drastic upregulation of the expression of virulence-associated genes and shifts metabolic pathway usage. In particular, high-level expression of toxins, such as cytolysins, proteases, and nucleases, was observed at infection sites. In addition, genes identified as consistently enriched included those related to metabolism of arginine and histidine as well as carbohydrate uptake and utilization. Conversely, genes associated with the oxidative stress response and cell division were consistently downregulated during infection. The present findings provide useful information for establishing novel treatment strategies.
坏死性筋膜炎是一种危及生命的皮下软组织感染， 是其主要病因。在宿主感染部位，宿主与细菌之间的局部环境和相互作用会影响细菌的基因表达谱，而与这种疾病相关的 基因表达模式尚不清楚。在这项研究中，我们使用了一种坏死性筋膜炎的小鼠模型，通过从感染后 24、48 和 96 小时获得的感染后腿中分离总 RNA，对 5448 株 M1T1 菌株进行了 RNA 测序 (RNA-seq) 分析。RNA-seq 分析结果确定了 483 个细菌基因，这些基因在感染后腿中的表达与对照条件下的表达一致。在感染过程中表现出一致富集的基因包括 306 个编码与毒力、碳水化合物利用、氨基酸代谢、痕量金属转运和液泡 ATP 酶转运系统相关的分子。令人惊讶的是，在本小鼠模型中观察到 3 个基因（编码链球菌溶血素 S 前体 ()、半胱氨酸蛋白酶 () 和分泌型 DNA 酶 () 的基因）的表达明显上调（对数倍变化 >6.0、>9.4 和 >7.1）。相反，一致下调的基因数量为 177 个，包括与氧化应激反应和细胞分裂相关的基因。这些结果表明，在坏死性筋膜炎中， 表现出改变的代谢、细胞增殖减少和主要毒素表达上调。我们的研究结果被认为提供了开发坏死性筋膜炎新的治疗策略和疫苗的关键信息。坏死性筋膜炎是一种危及生命的皮下软组织感染，主要由 引起。感染部位的炎症环境导致细菌的生存和发病机制发生全局基因表达变化。然而，目前尚未有关于坏死性筋膜炎中 转录组谱的研究。我们确定了 483 个细菌基因，其表达在感染过程中始终发生改变。我们的结果表明， 感染诱导与毒力相关基因的表达强烈上调，并改变代谢途径的利用。特别是，在感染部位观察到细胞溶解素、蛋白酶和核酸酶等毒素的高水平表达。此外，一致富集的基因包括与精氨酸和组氨酸代谢以及碳水化合物摄取和利用相关的基因。相反，与氧化应激反应和细胞分裂相关的基因在感染过程中一致下调。本研究结果为建立新的治疗策略提供了有用的信息。
