Society for Innovation and Development, Indian Institute of Science, Bengaluru, India.
PLoS One. 2013;8(3):e60013. doi: 10.1371/journal.pone.0060013. Epub 2013 Mar 27.
Staphylococcus aureus is a major human pathogen, first recognized as a leading cause of hospital-acquired infections. Community-associated S. aureus (CA-SA) pose a greater threat due to increase in severity of infection and disease among children and healthy adults. CA-SA strains in India are genetically diverse, among which is the sequence type (ST) 772, which has now spread to Australia, Europe and Japan. Towards understanding the genetic characteristics of ST772, we obtained draft genome sequences of five relevant clinical isolates and studied the properties of their PVL-carrying prophages, whose presence is a defining hallmark of CA-SA. We show that this is a novel prophage, which carries the structural genes of the hlb-carrying prophage and includes the sea enterotoxin. This architecture probably emerged early within the ST772 lineage, at least in India. The sea gene, unique to ST772 PVL, despite having promoter sequence characteristics typical of low expression, appears to be highly expressed during early phase of growth in laboratory conditions. We speculate that this might be a consequence of its novel sequence context. The crippled nature of the hlb-converting prophage in ST772 suggests that widespread mobility of the sea enterotoxin might be a selective force behind its 'transfer' to the PVL prophage. Wild type ST772 strains induced strong proliferative responses as well as high cytotoxic activity against neutrophils, likely mediated by superantigen SEA and the PVL toxin respectively. Both proliferation and cytotoxicity were markedly reduced in a cured ST772 strain indicating the impact of the phage on virulence. The presence of SEA alongside the genes for the immune system-modulating PVL toxin may contribute to the success and virulence of ST772.
金黄色葡萄球菌是一种主要的人类病原体，最初被认为是医院获得性感染的主要原因。社区相关性金黄色葡萄球菌（CA-SA）由于儿童和健康成年人感染和疾病的严重程度增加，构成了更大的威胁。印度的 CA-SA 菌株具有遗传多样性，其中包括序列类型（ST）772，现已传播到澳大利亚、欧洲和日本。为了了解 ST772 的遗传特征，我们获得了五个相关临床分离株的草图基因组序列，并研究了其携带 PVL 的前噬菌体的特性，前噬菌体的存在是 CA-SA 的一个决定性标志。我们表明，这是一种新型前噬菌体，携带 hlb 携带前噬菌体的结构基因，并包括 sea 肠毒素。这种结构可能在 ST772 谱系中很早就出现了，至少在印度是这样。sea 基因是 ST772 PVL 所特有的，尽管其启动子序列特征典型的低表达，但在实验室条件下的早期生长阶段似乎高度表达。我们推测这可能是其新序列结构的结果。ST772 中 hlb 转化前噬菌体的残缺性质表明，sea 肠毒素的广泛移动可能是其“转移”到 PVL 前噬菌体的选择力。野生型 ST772 菌株诱导强烈的增殖反应以及对中性粒细胞的高细胞毒性活性，这可能分别由超抗原 SEA 和 PVL 毒素介导。在经过治愈的 ST772 菌株中，增殖和细胞毒性都明显降低，表明噬菌体对毒力的影响。SEA 与调节免疫系统的 PVL 毒素基因的存在可能有助于 ST772 的成功和毒力。
