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SosA inhibits cell division in Staphylococcus aureus in response to DNA damage
- Source :
- Molecular Microbiology, Bojer, M S, Wacnik, K, Kjelgaard, P, Gallay, C, Bottomley, A L, Cohn, M T, Lindahl, G, Frees, D, Veening, J W, Foster, S J & Ingmer, H 2019, ' SosA inhibits cell division in Staphylococcus aureus in response to DNA damage ', Molecular Microbiology, vol. 112, no. 4, pp. 1116-1130 . https://doi.org/10.1111/mmi.14350, Molecular microbiology, vol. 112, no. 4, pp. 1116-1130
- Publication Year :
- 2019
- Publisher :
- Wiley, 2019.
-
Abstract
- Summary Inhibition of cell division is critical for viability under DNA‐damaging conditions. DNA damage induces the SOS response that in bacteria inhibits cell division while repairs are being made. In coccoids, such as the human pathogen, Staphylococcus aureus, this process remains poorly studied. Here, we identify SosA as the staphylococcal SOS‐induced cell division inhibitor. Overproduction of SosA inhibits cell division, while sosA inactivation sensitizes cells to genotoxic stress. SosA is a small, predicted membrane protein with an extracellular C‐terminal domain in which point mutation of residues that are conserved in staphylococci and major truncations abolished the inhibitory activity. In contrast, a minor truncation led to SosA accumulation and a strong cell division inhibitory activity, phenotypically similar to expression of wild‐type SosA in a CtpA membrane protease mutant. This suggests that the extracellular C‐terminus of SosA is required both for cell division inhibition and for turnover of the protein. Microscopy analysis revealed that SosA halts cell division and synchronizes the cell population at a point where division proteins such as FtsZ and EzrA are localized at midcell, and the septum formation is initiated but unable to progress to closure. Thus, our findings show that SosA is central in cell division regulation in staphylococci.<br />Staphylococcus aureus is a human pathogen and a model organism for cell division in spherical bacteria. We show that SosA is the DNA‐damage‐inducible cell‐division inhibitor in S. aureus responsible for cessation of the cell cycle prior to division plate completion. The extracellular domain of SosA appears essential for activity but is also a likely target for regulation by the CtpA protease. This represents the first description of a cell division inhibition process in coccoid bacteria.
- Subjects :
- Staphylococcus aureus
Cell division
DNA damage
Cell
Population
Mutant
Bacterial Proteins/metabolism
Cell Division/genetics
Cell Division/physiology
Cytoskeletal Proteins/metabolism
DNA Damage/genetics
DNA Damage/physiology
Membrane Proteins/metabolism
SOS Response, Genetics/genetics
SOS Response, Genetics/physiology
Staphylococcal Infections/metabolism
Staphylococcus aureus/genetics
Staphylococcus aureus/metabolism
Biology
medicine.disease_cause
Microbiology
03 medical and health sciences
Bacterial Proteins
Extracellular
medicine
Viability assay
SOS response
education
FtsZ
SOS Response, Genetics
Molecular Biology
Escherichia coli
Research Articles
030304 developmental biology
education.field_of_study
0303 health sciences
030306 microbiology
Membrane Proteins
Staphylococcal Infections
Cell biology
Cytoskeletal Proteins
medicine.anatomical_structure
biology.protein
Cell Division
DNA Damage
Research Article
Subjects
Details
- Language :
- English
- ISSN :
- 0950382X
- Database :
- OpenAIRE
- Journal :
- Molecular Microbiology, Bojer, M S, Wacnik, K, Kjelgaard, P, Gallay, C, Bottomley, A L, Cohn, M T, Lindahl, G, Frees, D, Veening, J W, Foster, S J & Ingmer, H 2019, ' SosA inhibits cell division in Staphylococcus aureus in response to DNA damage ', Molecular Microbiology, vol. 112, no. 4, pp. 1116-1130 . https://doi.org/10.1111/mmi.14350, Molecular microbiology, vol. 112, no. 4, pp. 1116-1130
- Accession number :
- edsair.doi.dedup.....640f65495731cc54abbda71e94c7ed97