Nature Microbiology ( IF 20.5 ) Pub Date : 2024-10-28 , DOI: 10.1038/s41564-024-01821-8 Félix Ramos-León, Brandon R. Anjuwon-Foster, Vivek Anantharaman, Taylor B. Updegrove, Colby N. Ferreira, Amany M. Ibrahim, Chin-Hsien Tai, Michael J. Kruhlak, Dominique M. Missiakas, Jodi L. Camberg, L. Aravind, Kumaran S. Ramamurthi
The bacterial pathogen, Staphylococcus aureus, grows by dividing in two alternating orthogonal planes. How these cell division planes are positioned correctly is not known. Here we used chemical genetic screening to identify PcdA as a division plane placement factor. Molecular biology and imaging approaches revealed non-orthogonal division plane selection for pcdA mutant bacteria. PcdA is a structurally and functionally altered member of the McrB AAA+ NTPase family, which are often found as restriction enzyme subunits. PcdA interacts with the tubulin-like divisome component, FtsZ, and the structural protein, DivIVA; it also localizes to future cell division sites. PcdA multimerization, localization and function are NTPase activity-dependent. We propose that the DivIVA/PcdA complex recruits unpolymerized FtsZ to assemble along the proper cell division plane. Although pcdA deletion did not affect S. aureus growth in several laboratory conditions, its clustered growth pattern was disrupted, sensitivity to cell-wall-targeting antibiotics increased and virulence in mice decreased. We propose that the characteristic clustered growth pattern of S. aureus, which emerges from dividing in alternating orthogonal division planes, might protect the bacterium from host defences.
中文翻译:
PcdA 促进金黄色葡萄球菌的正交划分平面选择
细菌病原体金黄色葡萄球菌通过分裂成两个交替的正交平面来生长。这些细胞分裂平面如何正确定位尚不清楚。在这里,我们使用化学遗传学筛选将 PcdA 鉴定为分裂平面放置因子。分子生物学和成像方法揭示了 pcdA 突变细菌的非正交分裂平面选择。PcdA 是 McrB AAA+ NTPase 家族中结构和功能改变的成员,通常以限制性内切酶亚基的形式出现。PcdA 与微管蛋白样分裂体成分 FtsZ 和结构蛋白 DivIVA 相互作用;它还定位于未来的细胞分裂位点。PcdA 多聚化、定位和功能与 NTPase 活性有关。我们提出 DivIVA/PcdA 复合物募集未聚合的 FtsZ 以沿适当的细胞分裂平面组装。尽管 pcdA 缺失在几种实验室条件下不会影响金黄色葡萄球菌的生长,但其成簇生长模式被破坏,对细胞壁靶向抗生素的敏感性增加,小鼠毒力降低。我们提出,金黄色葡萄球菌的特征性聚集生长模式,它是在交替的正交分割平面中分裂而出现的,可能保护细菌免受宿主防御。