Mycobacterium abscessus is an emerging and difficult-to-manage mycobacterial species that exhibits smooth (S) or rough (R) morphotypes. Disruption of glycopeptidolipid (GPL) production results in transition from S to R and severe lung disease. A structure-activity relationship study was undertaken to decipher the role of GPL glycosylation in morphotype transition and pathogenesis. Deletion of gtf3 uncovered the prominent role of the extra rhamnose in enhancing mannose receptor-mediated internalization of M. abscessus by macrophages. In contrast, the absence of the 6-deoxy-talose and the first rhamnose in mutants lacking gtf1 and gtf2, respectively, affected M abscessus phagocytosis but also resulted in the S-to-R transition. Strikingly, gtf1 and gtf2 mutants displayed a strong propensity to form cords and abscesses in zebrafish, leading to robust and lethal infection. Together, these results underscore the importance and differential contribution of GPL monosaccharides in promoting virulence and infection outcomes.

脓肿分枝杆菌是一种新兴且难以管理的分枝杆菌物种，表现出光滑 (S) 或粗糙 (R) 形态类型。糖肽脂 (GPL) 生产的中断导致从 S 到 R 的转变和严重的肺部疾病。进行了结构-活性关系研究以破译 GPL 糖基化在形态型转变和发病机制中的作用。删除gtf3揭示了额外鼠李糖在增强甘露糖受体介导的巨噬细胞对脓肿分枝杆菌内化方面的突出作用。相反，在缺乏gtf1和gtf2的突变体中，6-脱氧塔罗糖和第一鼠李糖的缺失分别影响了脓肿分枝杆菌吞噬作用，但也导致 S-to-R 转换。引人注目的是，gtf1和gtf2突变体在斑马鱼中表现出强烈的形成绳索和脓肿的倾向，导致强烈和致命的感染。总之，这些结果强调了 GPL 单糖在促进毒力和感染结果方面的重要性和不同的贡献。