SosA inhibits cell division in Staphylococcus aureus in response to DNA damage
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SosA inhibits cell division in Staphylococcus aureus in response to DNA damage. / Bojer, Martin S.; Wacnik, Katarzyna; Kjelgaard, Peter; Gallay, Clement; Bottomley, Amy L.; Cohn, Marianne T.; Lindahl, Gunnar; Frees, Dorte; Veening, Jan Willem; Foster, Simon J.; Ingmer, Hanne.
I: Molecular Microbiology, Bind 112, Nr. 4, 2019, s. 1116-1130.Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › fagfællebedømt
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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
Y1 - 2019
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
VL - 112
SP - 1116
EP - 1130
JO - Molecular Microbiology
JF - Molecular Microbiology
SN - 0950-382X
IS - 4
ER -
ID: 227873664