Staphylococcus aureus is a Gram-positive pathogen responsible for antibiotic-resistant infections. To identify vulnerabilities in cell envelope biogenesis that may overcome resistance, we enriched for S. aureus transposon mutants with defects in cell surface integrity or cell division by sorting for cells that stain with propidium iodide or have increased light-scattering properties, respectively. Transposon sequencing of the sorted populations identified more than 20 previously uncharacterized factors impacting these processes. Cells inactivated for one of these proteins, factor preventing extra Z-rings (FacZ, SAOUHSC_01855), showed aberrant membrane invaginations and multiple FtsZ cytokinetic rings. These phenotypes were suppressed in mutants lacking the conserved cell-division protein GpsB, which forms an interaction hub bridging envelope biogenesis factors with the cytokinetic ring in S. aureus. FacZ was found to interact directly with GpsB in vitro and in vivo. We therefore propose that FacZ is an envelope biogenesis factor that antagonizes GpsB function to prevent aberrant division events in S. aureus.

金黄色葡萄球菌是一种导致抗生素耐药性感染的革兰氏阳性病原体。为了确定细胞包膜生物发生中可能克服耐药性的漏洞，我们通过分别分选用碘化丙啶染色或具有增强的光散射特性的细胞，富集了具有细胞表面完整性或细胞分裂缺陷的金黄色葡萄球菌转座子突变体。对分选群体进行转座子测序，发现了 20 多个先前未表征的影响这些过程的因素。这些蛋白质之一（防止额外 Z 环的因子（FacZ，SAOUHSC_01855））失活的细胞显示出异常的膜内陷和多个 FtsZ 细胞因子环。这些表型在缺乏保守细胞分裂蛋白 GpsB 的突变体中受到抑制，GpsB 形成桥接包膜生物发生因子与金黄色葡萄球菌细胞因子环的相互作用枢纽。发现 FacZ 在体外和体内直接与 GpsB 相互作用。因此，我们认为 FacZ 是一种包膜生物发生因子，可拮抗 GpsB 功能以防止金黄色葡萄球菌中的异常分裂事件。