CozEa and CozEb play overlapping and essential roles in controlling cell division in Staphylococcus aureus

Mol Microbiol. 2018 Sep;109(5):615-632. doi: 10.1111/mmi.13999. Epub 2018 Sep 26.

Abstract

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 and possibly influence localization of the cell division protein EzrA. 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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Bacterial Proteins / genetics
  • Bacterial Proteins / physiology*
  • Cell Cycle Proteins / genetics
  • Cell Cycle Proteins / metabolism*
  • Cell Division / genetics*
  • Clustered Regularly Interspaced Short Palindromic Repeats / genetics
  • DNA, Bacterial / genetics
  • Gene Knockdown Techniques
  • Membrane Proteins / genetics
  • Membrane Proteins / physiology*
  • Mutation
  • Staphylococcus aureus / genetics
  • Staphylococcus aureus / pathogenicity
  • Staphylococcus aureus / physiology*

Substances

  • Bacterial Proteins
  • Cell Cycle Proteins
  • DNA, Bacterial
  • Membrane Proteins