The ClpX chaperone and a hypermorphic FtsA variant with impaired self-interaction are mutually compensatory for coordinating Staphylococcus aureus cell division

Mol Microbiol. 2024 Jan;121(1):98-115. doi: 10.1111/mmi.15200. Epub 2023 Dec 1.

Abstract

Bacterial cell division requires the coordinated assembly and disassembly of a large protein complex called the divisome; however, the exact role of molecular chaperones in this critical process remains unclear. We here provide genetic evidence that ClpX unfoldase activity is a determinant for proper coordination of bacterial cell division by showing the growth defect of a Staphylococcus aureus clpX mutant is rescued by a spontaneously acquired G325V substitution in the ATP-binding domain of the essential FtsA cell division protein. The polymerization state of FtsA is thought to control initiation of bacterial septum synthesis and, while restoring the aberrant FtsA dynamics in clpX cells, the FtsAG325V variant displayed reduced ability to interact with itself and other cell division proteins. In wild-type cells, the ftsAG325V allele shared phenotypes with Escherichia coli superfission ftsA mutants and accelerated the cell cycle, increased the risk of daughter cell lysis, and conferred sensitivity to heat and antibiotics inhibiting cell wall synthesis. Strikingly, lethality was mitigated by spontaneous mutations that inactivate ClpX. Taken together, our results suggest that ClpX promotes septum synthesis by antagonizing FtsA interactions and illuminates the critical role of a protein unfoldase in coordinating bacterial cell division.

Keywords: Staphylococcus aureus; AAA+ ATPases; ClpX; FtsA; cell division; peptidoglycan.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • ATPases Associated with Diverse Cellular Activities / genetics
  • Bacterial Proteins / metabolism
  • Cell Division / genetics
  • Endopeptidase Clp / genetics
  • Endopeptidase Clp / metabolism
  • Escherichia coli / metabolism
  • Escherichia coli Proteins* / metabolism
  • Humans
  • Molecular Chaperones / genetics
  • Molecular Chaperones / metabolism
  • Staphylococcal Infections*
  • Staphylococcus aureus / metabolism

Substances

  • Bacterial Proteins
  • Endopeptidase Clp
  • Escherichia coli Proteins
  • FtsA protein, E coli
  • ClpX protein, E coli
  • ATPases Associated with Diverse Cellular Activities
  • Molecular Chaperones