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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 FtsA G325V variant displayed reduced ability to interact with itself and other cell division proteins. In wild-type cells, the ftsA G325V 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.

Titel:	The ClpX chaperone and a hypermorphic FtsA variant with impaired self-interaction are mutually compensatory for coordinating Staphylococcus aureus cell division.
Autor/in / Beteiligte Person:	Henriksen, C ; Baek, KT ; Wacnik, K ; Gallay, C ; Veening, JW ; Foster, SJ ; Frees, D
Link:	Full Text Finder (Volltext)
Zeitschrift:	Molecular microbiology, Jg. 121 (2024), Heft 1, S. 98-115
Veröffentlichung:	Oxford, OX ; Boston, MA : Blackwell Scientific Publications, c1987-, 2024
Medientyp:	academicJournal
ISSN:	1365-2958 (electronic)
DOI:	10.1111/mmi.15200
Schlagwort:	Humans Bacterial Proteins metabolism Endopeptidase Clp genetics Endopeptidase Clp metabolism Staphylococcus aureus metabolism Cell Division genetics Escherichia coli metabolism ATPases Associated with Diverse Cellular Activities genetics Molecular Chaperones genetics Molecular Chaperones metabolism Escherichia coli Proteins metabolism Staphylococcal Infections
Sonstiges:	Nachgewiesen in: MEDLINE Sprachen: English Publication Type: Journal Article; Research Support, Non-U.S. Gov't Language: English [Mol Microbiol] 2024 Jan; Vol. 121 (1), pp. 98-115. <i>Date of Electronic Publication: </i>2023 Dec 01. MeSH Terms: Escherichia coli Proteins* / metabolism ; Staphylococcal Infections* ; Humans ; Bacterial Proteins / metabolism ; Endopeptidase Clp / genetics ; Endopeptidase Clp / metabolism ; Staphylococcus aureus / metabolism ; Cell Division / genetics ; Escherichia coli / metabolism ; ATPases Associated with Diverse Cellular Activities / genetics ; Molecular Chaperones / genetics ; Molecular Chaperones / metabolism References: Aziz, R.K., Bartels, D., Best, A.A., DeJongh, M., Disz, T., Edwards, R.A. et al. (2008) The RAST Server: rapid annotations using subsystems technology. BMC Genomics, 9, 75. ; Baek, K., Gründling, A., Mogensen, R.G., Thøgersen, L., Petersen, A., Paulander, W. et al. 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Grant Information: 212197/Z/19/Z United Kingdom WT_ Wellcome Trust Contributed Indexing: Keywords: Staphylococcus aureus; AAA+ ATPases; ClpX; FtsA; cell division; peptidoglycan Substance Nomenclature: 0 (Bacterial Proteins) ; EC 3.4.21.92 (Endopeptidase Clp) ; 0 (Escherichia coli Proteins) ; 0 (FtsA protein, E coli) ; EC 3.6.1.3 (ClpX protein, E coli) ; EC 3.6.4.- (ATPases Associated with Diverse Cellular Activities) ; 0 (Molecular Chaperones) Entry Date(s): Date Created: 20231202 Date Completed: 20240115 Latest Revision: 20240412 Update Code: 20240412

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