Staphylococcus pseudintermedius is a major canine pathogen but also occasionally colonizes and infects humans. Multidrug-resistant methicillin-resistant S. pseudintermedius (MDR MRSP) strains have emerged globally, making treatment and control of this pathogen challenging. Sequence type 71 (ST71), ST68, and ST45 are the most widespread and successful MDR MRSP clones. The potential genetic factors underlying the clonal success of these and other predominant clones remain unknown. Characterization of the pangenome, lineage-associated accessory genes, and genes acquired through horizontal gene transfer from other bacteria is important for identifying such factors. Here, we analyzed genome sequence data from 622 S. pseudintermedius isolates to investigate the evolution of pathogenicity across lineages. We show that the predominant clones carry one or more lineage-associated virulence genes. The gene encoding staphylococcal protein A (SpA), a key virulence factor involved in immune evasion and a potential vaccine antigen, is deleted in 62% of isolates. Most importantly, we have discovered that the spa locus is a hot spot for recombination and horizontal gene transfer in S. pseudintermedius, where genes related to restriction modification, prophage immunity, mercury resistance, and nucleotide and carbohydrate metabolism have been acquired in different lineages. Our study also establishes that ST45 is composed of two distinct sublineages that differ in their accessory gene content and virulence potential. Collectively, this study reports several previously undetected lineage-associated genetic factors that may have a role in the clonal success of the major MDR MRSP clones. These data provide a framework for future experimental studies on S. pseudintermedius pathogenesis and for developing novel therapeutics against this pathogen.

中文翻译：

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葡萄球菌蛋白 A (spa) 基因座是假中间葡萄球菌重组和水平基因转移的热点

假中间葡萄球菌是一种主要的犬病原体，但偶尔也会定殖和感染人类。耐多药甲氧西林假中间链球菌(MDR MRSP) 菌株已在全球范围内出现，这使得对该病原体的治疗和控制具有挑战性。序列类型 71 (ST71)、ST68 和 ST45 是最广泛和最成功的 MDR MRSP 克隆。这些和其他主要克隆的克隆成功背后的潜在遗传因素仍然未知。泛基因组、谱系相关辅助基因和通过其他细菌水平基因转移获得的基因的表征对于识别这些因素很重要。在这里，我们分析了来自 622 S. pseudintermedius 的基因组序列数据分离株以研究跨谱系致病性的演变。我们表明主要克隆携带一个或多个谱系相关的毒力基因。编码葡萄球菌蛋白 A (SpA) 的基因（参与免疫逃避和潜在疫苗抗原的关键毒力因子）在 62% 的分离株中被删除。最重要的是，我们发现spa基因座是S. pseudintermedius 中重组和水平基因转移的热点，其中与限制性修饰、原噬菌体免疫、汞抗性以及核苷酸和碳水化合物代谢相关的基因已在不同谱系中获得。我们的研究还确定 ST45 由两个不同的亚系组成，它们的辅助基因含量和毒力潜力不同。总的来说，这项研究报告了几个以前未检测到的谱系相关遗传因素，这些因素可能在主要 MDR MRSP 克隆的克隆成功中起作用。这些数据为未来关于S. pseudintermedius发病机制的实验研究和开发针对这种病原体的新疗法提供了框架。