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Large-Scale Screening and Identification of Novel Pathogenic Staphylococcus aureus Genes Using a Silkworm Infection Model.
The Journal of Infectious Diseases ( IF 6.4 ) Pub Date : 2020-05-11 , DOI: 10.1093/infdis/jiaa004
Atmika Paudel 1 , Hiroshi Hamamoto 1 , Suresh Panthee 1 , Yasuhiko Matsumoto 1 , Kazuhisa Sekimizu 1
Affiliation  

The regulatory network of virulence factors produced by the opportunistic pathogen Staphylococcus aureus is unclear and the functions of many uncharacterized genes in its genome remain to be elucidated. In this study, we screened 380 genes whose function was unassigned, utilizing gene-disrupted transposon mutants of the community-acquired methicillin-resistant S. aureus USA300 for pathogenicity in silkworms. We identified 10 strains with reduced silkworm killing ability. Among them, 8 displayed reduced virulence in a mouse model as evidenced by reduced colony-forming units in organs of infected mice. The role of each gene in pathogenicity was further confirmed by complementation and pathogenicity tests in silkworms, where we found that the phenotype was not restored in 1 strain. Additionally, some of the mutants displayed reduced hemolysis, proteolysis, pigment production, and survival in murine RAW 264.7 monocyte-macrophage cells. These newly identified genes involved in virulence will enhance our understanding of the pathogenicity of S. aureus.

中文翻译:

使用家蚕感染模型大规模筛选和鉴定新型致病性金黄色葡萄球菌基因。

由机会病原体金黄色葡萄球菌产生的毒力因子的调节网络尚不清楚,其基因组中许多未鉴定基因的功能仍有待阐明。在这项研究中,我们利用社区获得的耐甲氧西林金黄色葡萄球菌USA300的基因破坏的转座子突变体,筛选了380个功能未确定的基因,以确定其在蚕中的致病性。我们鉴定了10种家蚕杀伤能力降低的菌株。在它们当中,有8个在小鼠模型中显示出降低的毒力,这可以通过感染小鼠器官中集落形成单位的减少来证明。通过在蚕中进行互补和致病性测试进一步证实了每个基因在致病性中的作用,我们发现该表型在1个菌株中未恢复。此外,某些突变体显示出减少的溶血作用,蛋白水解,色素生成和在鼠RAW 264.7单核巨噬细胞中的存活。这些新发现的与毒力有关的基因将增强我们对金黄色葡萄球菌致病性的了解。
更新日期:2020-01-08
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