Department of Pathobiology, Ontario Veterinary College, University of Guelph, Ontario, Canada.
Anim Health Res Rev. 2011 Jun;12(1):33-45. doi: 10.1017/S1466252311000065.
Persistent or difficult-to-treat Staphylococcus aureus infections in animals and humans may be related to small colony variants (SCVs) that can hide inside host cells and modulate host defenses. S. aureus SCVs have gained much attention in human medicine but have been underestimated and overlooked in veterinary medicine. Recently, an SCV isolated from a dairy cow with a history of chronic mastitis was shown to possess similar phenotypic and transcriptomic properties to those of human SCVs. SCVs form small, colorless, non-hemolytic colonies after 48 h, are only slowly coagulase positive, fail to ferment mannitol, and can revert to the parental phenotype. The phenotype of SCVs is mostly related to alterations in hemin and/or menadione biosynthesis or to thymidine deficiency. Transcriptomic analysis of SCVs shows up-regulation of genes involved in glycolytic and arginine-deiminase pathways, capsular biosynthesis; increased sigma B activity; and down-regulation of genes for α-hemolysin, coagulase and effector molecule RNA III of the global virulence regulator Agr. Similar results are reported at the protein level. SCVs are less virulent but successful persisters in infection models. SCVs persist longer and at higher numbers within non-phagocytes than do their parents. SCVs survive within spacious vacuoles up to 24 h within cultured bovine mammary epithelial cells, likely due to up-regulation of protective mechanisms that counteract the lethal acidic environment of the phagolysosome. Persistence of SCVs within host cells may explain failures in antimicrobial therapy and vaccinations.
动物和人类中持续性或难以治疗的金黄色葡萄球菌感染可能与能够隐藏在宿主细胞内并调节宿主防御的小菌落变异体 (SCV) 有关。金黄色葡萄球菌 SCV 在人类医学中引起了广泛关注，但在兽医医学中却被低估和忽视。最近，从患有慢性乳腺炎的奶牛中分离出的一株 SCV 被证明具有与人类 SCV 相似的表型和转录组特性。SCV 在 48 小时后形成小的、无色的、非溶血的菌落，仅缓慢凝固酶阳性，不能发酵甘露醇，并且可以回复为亲本表型。SCV 的表型主要与血红素和/或甲萘醌生物合成或胸苷缺乏的改变有关。SCV 的转录组分析显示参与糖酵解和精氨酸脱氨酶途径、荚膜生物合成的基因上调；σB 活性增加；α-溶血素、凝固酶和全局毒力调节剂 Agr 的效应分子 RNAIII 的基因下调。在蛋白质水平也报告了类似的结果。SCV 在感染模型中的毒力较低，但能成功地作为持久存者。与亲本相比，SCV 在非吞噬细胞中持续存在的时间更长，数量更多。SCV 在培养的牛乳腺上皮细胞中能在大空泡中存活长达 24 小时，可能是由于上调了保护性机制，这些机制抵消了吞噬体溶酶体的致死酸性环境。SCV 在宿主细胞内的持续存在可能解释了抗菌治疗和疫苗接种的失败。
