SosA inhibits cell division in Staphylococcus aureus in response to DNA damage

TY - JOUR

T1 - SosA inhibits cell division in Staphylococcus aureus in response to DNA damage

AU - Bojer, Martin S.

AU - Wacnik, Katarzyna

AU - Kjelgaard, Peter

AU - Gallay, Clement

AU - Bottomley, Amy L.

AU - Cohn, Marianne T.

AU - Lindahl, Gunnar

AU - Frees, Dorte

AU - Veening, Jan Willem

AU - Foster, Simon J.

AU - Ingmer, Hanne

PY - 2019/10/1

Y1 - 2019/10/1

N2 - 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.

AB - 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.

U2 - 10.1111/mmi.14350

DO - 10.1111/mmi.14350

M3 - Journal article

C2 - 31290194

AN - SCOPUS:85070757262

SN - 0950-382X

VL - 112

SP - 1116

EP - 1130

JO - Molecular Microbiology

JF - Molecular Microbiology

IS - 4

ER -