RT Journal Article SR Electronic T1 CozEa and CozEb play overlapping and essential roles in controlling cell division in Staphylococcus aureus JF bioRxiv FD Cold Spring Harbor Laboratory SP 256560 DO 10.1101/256560 A1 Gro Anita Stamsås A1 Ine Storaker Myrbråten A1 Daniel Straume A1 Zhian Salehian A1 Jan-Willem Veening A1 Leiv Sigve Håvarstein A1 Morten Kjos YR 2018 UL http://biorxiv.org/content/early/2018/05/23/256560.abstract AB Staphylococcus aureus needs to control the position and timing of cell division and cell wall synthesis to maintain its spherical shape. We identified two membrane proteins, named CozEa and CozEb, which together are important for proper cell division in S. aureus. CozEa and CozEb are homologs of the cell elongation regulator CozESpn of Streptococcus pneumoniae. While cozEa and cozEb were not essential individually, the ΔcozEaΔcozEb double mutant was lethal. To study the functions of cozEa and cozEb, we constructed a CRISPR interference (CRISPRi) system for S. aureus, allowing transcriptional knockdown of essential genes. CRISPRi knockdown of cozEa in the ΔcozEb strain (and vice versa) causes cell morphological defects and aberrant nucleoid staining, showing that cozEa and cozEb have overlapping functions and are important for normal cell division. We found that CozEa and CozEb interact with the cell division protein EzrA, and that EzrA-GFP mislocalizes in the absence of CozEa and CozEb. Furthermore, the CozE-EzrA interaction is conserved in S. pneumoniae, and cell division is mislocalized in cozESpn-depleted S. pneumoniae cells. Together, our results show that CozE proteins mediate control of cell division in S. aureus and S. pneumoniae, likely via interactions with key cell division proteins such as EzrA.