小菌落变异株（small colony variant，SCV）是金黄色葡萄球菌等细菌在环境选择性压力下产生的特殊表型变异体，具有生长缓慢、色素合成减少、营养缺陷、耐药性增强以及易于细胞内定植和形成生物膜等独特的生物学特性。近年来，研究人员逐渐发现SCV在感染的慢性化进程和不良预后中扮演着关键角色。SCV群体表现出显著的异质性，其分子特征复杂多样。与野生型菌株相比，SCV毒力低下，黏附性显著增强，可有效逃避免疫系统的识别和清除。SCV通过侵入巨噬细胞等细胞内并形成无症状的休眠体，引起机体对抗菌药物耐药，在周围环境改善时可恢复为野生型细菌，造成骨髓炎、囊性纤维化、内植物感染等迁延不愈。但目前SCV治疗仅限于长期抗生素治疗联合感染部位清创处理，关于SCV及其致病机制与治疗认识依然不明确。传统疗法如利福平联合万古霉素对胞内SCV疗效有限，新型策略比如靶向ATP合酶抑制剂（如番茄红素）或纳米载体递送抗生素以增强胞内渗透、碱化微环境或者物理疗法破坏生物膜等将成为攻克SCV相关感染的重要突破口。该文总结了SCV的生物学特征、致病机制与治疗研究进展，为SCV相关感染的研究和治疗提供参考。

Small colony variants (SCVs) are unique phenotypic variants produced by bacteria such as Staphylococcus aureus under environmental selective pressure, with specific biological characteristics, including slow growth, reduced pigment synthesis, auxotrophy, enhanced drug resistance, and easier intracellular colonization and biofilm formation. In recent years, it has been increasingly recognized that SCVs play a crucial role in the chronic progression of infections and poor prognosis. SCVs exhibit significant heterogeneity with complex and diverse molecular profiles. Compared with wild-type strains, SCVs have low virulence and significantly enhanced adherence, and they can effectively evade immune system recognition and clearance. SCVs invade host cells, including macrophages, and form dormant intracellular forms, causing antimicrobial resistance. These variants can revert to wild-type bacteria when environmental conditions improve, causing persistent and refractory infections such as osteomyelitis, cystic fibrosis, and implant-associated infections. However, current treatments for SCV-related infections are limited to long-term antibiotic therapy combined with debridement of infected tissue, and understanding of SCVs, their pathogenic mechanisms, and treatments remains limited. Traditional therapies, such as rifampicin combined with vancomycin, have limited efficacy against intracellular SCVs. Novel strategies, such as targeting ATP synthase inhibitors (eg. lycopene), using nanocarrier-delivered antibiotics to enhance intracellular penetration, alkalinizing of the microenvironment, or disrupting biofilms by physical therapies, are important breakthroughs in the fight against SCV-associated infections. This paper summarizes the biological characteristics, pathogenic mechanisms, and therapeutic progress of SCVs, providing reference for research and treatment of SCV-related infections.