Paudel Atmika, Hamamoto Hiroshi, Panthee Suresh, Matsumoto Yasuhiko, Sekimizu Kazuhisa
Institute of Medical Mycology, Teikyo University, Tokyo, Japan.
J Infect Dis. 2020 May 11;221(11):1795-1804. doi: 10.1093/infdis/jiaa004.
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.
机会致病菌金黄色葡萄球菌产生的毒力因子调控网络尚不清楚，其基因组中许多未表征基因的功能仍有待阐明。在本研究中，我们利用社区获得性耐甲氧西林金黄色葡萄球菌USA300的基因破坏转座子突变体，筛选了380个功能未明确的基因，研究其对家蚕的致病性。我们鉴定出10株家蚕致死能力降低的菌株。其中8株在小鼠模型中显示出毒力降低，感染小鼠器官中的菌落形成单位减少证明了这一点。通过在家蚕中进行互补和致病性试验，进一步证实了每个基因在致病性中的作用，我们发现其中1株的表型未恢复。此外，一些突变体在小鼠RAW 264.7单核巨噬细胞中的溶血、蛋白水解、色素产生和存活能力降低。这些新鉴定的与毒力相关的基因将增进我们对金黄色葡萄球菌致病性的理解。
