Sparks Ian L, Kado Takehiro, Prithviraj Malavika, Nijjer Japinder, Yan Jing, Morita Yasu S
Department of Microbiology, University of Massachusetts, Amherst, MA, USA.
Department of Molecular, Cellular and Developmental Biology, Yale University, New Haven, CT, USA.
Nat Commun. 2024 Mar 11;15(1):2191. doi: 10.1038/s41467-024-46565-5.
The growth and division of mycobacteria, which include clinically relevant pathogens, deviate from that of canonical bacterial models. Despite their Gram-positive ancestry, mycobacteria synthesize and elongate a diderm envelope asymmetrically from the poles, with the old pole elongating more robustly than the new pole. The phosphatidylinositol-anchored lipoglycans lipomannan (LM) and lipoarabinomannan (LAM) are cell envelope components critical for host-pathogen interactions, but their physiological functions in mycobacteria remained elusive. In this work, using biosynthetic mutants of these lipoglycans, we examine their roles in maintaining cell envelope integrity in Mycobacterium smegmatis and Mycobacterium tuberculosis. We find that mutants defective in producing mature LAM fail to maintain rod cell shape specifically at the new pole and para-septal regions whereas a mutant that produces a larger LAM becomes multi-septated. Therefore, LAM plays critical and distinct roles at subcellular locations associated with division in mycobacteria, including maintenance of local cell wall integrity and septal placement.
分枝杆菌包括具有临床相关性的病原体，其生长和分裂与典型细菌模型不同。尽管分枝杆菌起源于革兰氏阳性菌，但它们从两极不对称地合成并延长双层包膜，旧极比新极生长得更旺盛。磷脂酰肌醇锚定的脂多糖脂甘露聚糖（LM）和脂阿拉伯甘露聚糖（LAM）是细胞包膜成分，对宿主-病原体相互作用至关重要，但其在分枝杆菌中的生理功能仍不清楚。在这项研究中，我们利用这些脂多糖的生物合成突变体，研究它们在耻垢分枝杆菌和结核分枝杆菌中维持细胞包膜完整性的作用。我们发现，在产生成熟LAM方面存在缺陷的突变体无法在新极和旁隔膜区域维持杆状细胞形状，而产生更大LAM的突变体则会出现多个隔膜。因此，LAM在分枝杆菌中与分裂相关的亚细胞位置发挥关键且独特的作用，包括维持局部细胞壁完整性和隔膜定位。
