Skip to main content
SpringerLink
Log in

SosA in Staphylococci: an addition to the paradigm of membrane-localized, SOS-induced cell division inhibition in bacteria

  • Mini-Review
  • Published:
Current Genetics Aims and scope Submit manuscript

Abstract

In all living organisms, genome replication and cell division must be coordinated to produce viable offspring. In the event of DNA damage, bacterial cells employ the SOS response to simultaneously express damage repair systems and halt cell division. Extensive characterization of SOS-controlled cell division inhibition in Escherichia coli has laid the ground for a long-standing paradigm where the cytosolic SulA protein inhibits polymerization of the central division protein, FtsZ, and thereby prevents recruitment of the division machinery at the future division site. Within the last decade, it has become clear that another, likely more general, paradigm exists, at least within the broad group of Gram-positive bacterial species, namely membrane-localized, SOS-induced cell division inhibition. We recently identified such an inhibitor in Staphylococci, SosA, and established a model for SosA-mediated cell division inhibition in Staphylococcus aureus in response to DNA damage. SosA arrests cell division subsequent to the septal localization of FtsZ and later membrane-bound division proteins, while preventing progression to septum closure, leading to synchronization of cells at this particular stage. A membrane-associated protease, CtpA negatively regulates SosA activity and likely allows growth to resume once conditions are favorable. Here, we provide a brief summary of our findings in the context of what already is known for other membrane cell division inhibitors and we emphasize how poorly characterized these intriguing processes are mechanistically. Furthermore, we put some perspective on the relevance of our findings and future developments within the field.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1

Similar content being viewed by others

References

  • Aarsman ME, Piette A, Fraipont C, Vinkenvleugel TM, Nguyen-Distèche M, den Blaauwen T (2005) Maturation of the Escherichia coli divisome occurs in two steps. Mol Microbiol 55:1631–1645

    Article  CAS  PubMed  Google Scholar 

  • Adams DW, Errington J (2009) Bacterial cell division: assembly, maintenance and disassembly of the Z ring. Nat Rev Microbiol 7:642–653

    Article  CAS  PubMed  Google Scholar 

  • Anderson KL, Roberts C, Disz T, Vonstein V, Hwang K, Overbeek R, Olson PD, Projan SJ, Dunman PM (2006) Characterization of the Staphylococcus aureus heat shock, cold shock, stringent, and SOS responses and their effects on log-phase mRNA turnover. J Bacteriol 188:6739–6756

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Baharoglu Z, Mazel D (2014) SOS, the formidable strategy of bacteria against aggressions. FEMS Microbiol Rev 38:1126–1145

    Article  CAS  PubMed  Google Scholar 

  • Bojer MS, Wacnik K, Kjelgaard P, Gallay C, Bottomley AL, Cohn MT, Lindahl G, Frees D, Veening JW, Foster SJ, Ingmer H (2019) SosA inhibits cell division in Staphylococcus aureus in response to DNA damage. Mol Microbiol 112:1116–1130

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Buchholz M, Nahrstedt H, Pillukat MH, Deppe V, Meinhardt F (2013) yneA mRNA instability is involved in temporary inhibition of cell division during the SOS response of Bacillus megaterium. Microbiology 159:1564–1574

    Article  CAS  PubMed  Google Scholar 

  • Burby PE, Simmons LA (2020) Regulation of cell division in bacteria by monitoring genome integrity and DNA replication status. J Bacteriol 202:e00408-19

    Article  Google Scholar 

  • Burby PE, Simmons ZW, Schroeder JW, Simmons LA (2018) Discovery of a dual protease mechanism that promotes DNA damage checkpoint recovery. PLoS Genet 14:e1007512

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Chauhan A, Lofton H, Maloney E, Moore J, Fol M, Madiraju MV, Rajagopalan M (2006) Interference of Mycobacterium tuberculosis cell division by Rv2719c, a cell wall hydrolase. Mol Microbiol 62:132–147

    Article  CAS  PubMed  Google Scholar 

  • Cirz RT, Jones MB, Gingles NA, Minogue TD, Jarrahi B, Peterson SN, Romesberg FE (2007) Complete and SOS-mediated response of Staphylococcus aureus to the antibiotic ciprofloxacin. J Bacteriol 189:531–539

    Article  CAS  PubMed  Google Scholar 

  • Cohn MT, Kjelgaard P, Frees D, Penadés JR, Ingmer H (2011) Clp-dependent proteolysis of the LexA N-terminal domain in Staphylococcus aureus. Microbiology 157:677–684

    Article  CAS  PubMed  Google Scholar 

  • Cordell SC, Robinson EJ, Lowe J (2003) Crystal structure of the SOS cell division inhibitor SulA and in complex with FtsZ. Proc Natl Acad Sci USA 100:7889–7894

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Culyba MJ (2019) Ordering up gene expression by slowing down transcription factor binding kinetics. Curr Genet 65:401–406

    Article  CAS  PubMed  Google Scholar 

  • den Blaauwen T, Luirink J (2019) Checks and balances in bacterial cell division. MBio 10:e00149–e219

    Google Scholar 

  • den Blaauwen T, Andreu JM, Monasterio O (2014) Bacterial cell division proteins as antibiotic targets. Bioorg Chem 55:27–38

    Article  CAS  Google Scholar 

  • Escobar CA, Cross TA (2018) False positives in using the zymogram assay for identification of peptidoglycan hydrolases. Anal Biochem 543:162–166

    Article  CAS  PubMed  Google Scholar 

  • Gamba P, Veening JW, Saunders NJ, Hamoen LW, Daniel RA (2009) Two-step assembly dynamics of the Bacillus subtilis divisome. J Bacteriol 191:4186–4194

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Henrikus SS, van Oijen AM, Robinson A (2018) Specialised DNA polymerases in Escherichia coli: roles within multiple pathways. Curr Genet 64:1189–1196

    Article  CAS  PubMed  Google Scholar 

  • Higashitani A, Higashitani N, Horiuchi K (1995) A cell division inhibitor SulA of Escherichia coli directly interacts with FtsZ through GTP hydrolysis. Biochem Biophys Res Commun 209:198–204

    Article  CAS  PubMed  Google Scholar 

  • Huisman O, D'Ari R (1981) An inducible DNA replication-cell division coupling mechanism in E. coli. Nature 290:797–799

    Article  CAS  PubMed  Google Scholar 

  • Huisman O, D'Ari R, Gottesman S (1984) Cell-division control in Escherichia coli: specific induction of the SOS function SfiA protein is sufficient to block septation. Proc Natl Acad Sci USA 81:4490–4494

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Kawai Y, Moriya S, Ogasawara N (2003) Identification of a protein, YneA, responsible for cell division suppression during the SOS response in Bacillus subtilis. Mol Microbiol 47:1113–1122

    Article  CAS  PubMed  Google Scholar 

  • Kelley WL (2006) Lex marks the spot: the virulent side of SOS and a closer look at the LexA regulon. Mol Microbiol 62:1228–1238

    Article  CAS  PubMed  Google Scholar 

  • Kreuzer KN (2013) DNA damage responses in prokaryotes: regulating gene expression, modulating growth patterns, and manipulating replication forks. Cold Spring Harb Perspect Biol 5:a012674

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Lock RL, Harry EJ (2008) Cell-division inhibitors: new insights for future antibiotics. Nat Rev Drug Discov 7:324–338

    Article  CAS  PubMed  Google Scholar 

  • Mizusawa S, Gottesman S (1983) Protein degradation in Escherichia coli: the lon gene controls the stability of sulA protein. Proc Natl Acad Sci USA 80:358–362

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Mo AH, Burkholder WF (2010) YneA, an SOS-induced inhibitor of cell division in Bacillus subtilis, is regulated posttranslationally and requires the transmembrane region for activity. J Bacteriol 192:3159–3173

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Modell JW, Hopkins AC, Laub MT (2011) A DNA damage checkpoint in Caulobacter crescentus inhibits cell division through a direct interaction with FtsW. Genes Dev 25:1328–1343

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Mukherjee A, Cao C, Lutkenhaus J (1998) Inhibition of FtsZ polymerization by SulA, an inhibitor of septation in Escherichia coli. Proc Natl Acad Sci USA 95:2885–2890

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Ogino H, Teramoto H, Inui M, Yukawa H (2008) DivS, a novel SOS-inducible cell-division suppressor in Corynebacterium glutamicum. Mol Microbiol 67:597–608

    Article  CAS  PubMed  Google Scholar 

  • Radman M (1975) SOS repair hypothesis: phenomenology of an inducible DNA repair which is accompanied by mutagenesis. Basic Life Sci 5A:355–367

    CAS  PubMed  Google Scholar 

  • Reichmann NT, Tavares AC, Saraiva BM, Jousselin A, Reed P, Pereira AR, Monteiro JM, Sobral RG, VanNieuwenhze MS, Fernandes F, Pinho MG (2019) SEDS-bPBP pairs direct lateral and septal peptidoglycan synthesis in Staphylococcus aureus. Nat Microbiol 4:1368–1377

    Article  CAS  PubMed  Google Scholar 

  • Schoemaker JM, Gayda RC, Markovitz A (1984) Regulation of cell division in Escherichia coli: SOS induction and cellular location of the SulA protein, a key to lon-associated filamentation and death. J Bacteriol 158:551–561

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Seong IS, Oh JY, Yoo SJ, Seol JH, Chung CH (1999) ATP-dependent degradation of SulA, a cell division inhibitor, by the HslVU protease in Escherichia coli. FEBS Lett 456:211–214

    Article  CAS  PubMed  Google Scholar 

  • Söderström B, Daley DO (2017) The bacterial divisome: more than a ring? Curr Genet 63:161–164

    Article  PubMed  CAS  Google Scholar 

  • Söderström B, Chan H, Daley DO (2019) Super-resolution images of peptidoglycan remodelling enzymes at the division site of Escherichia coli. Curr Genet 65:99–101

    Article  PubMed  CAS  Google Scholar 

  • Sonezaki S, Ishii Y, Okita K, Sugino T, Kondo A, Kato Y (1995) Overproduction and purification of SulA fusion protein in Escherichia coli and its degradation by Lon protease in vitro. Appl Microbiol Biotechnol 43:304–309

    Article  CAS  PubMed  Google Scholar 

  • Taguchi A, Welsh MA, Marmont LS, Lee W, Sjodt M, Kruse AC, Kahne D, Bernhardt TG, Walker S (2019) FtsW is a peptidoglycan polymerase that is functional only in complex with its cognate penicillin-binding protein. Nat Microbiol 4:587–594

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Trusca D, Scott S, Thompson C, Bramhill D (1998) Bacterial SOS checkpoint protein SulA inhibits polymerization of purified FtsZ cell division protein. J Bacteriol 180:3946–3953

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Vadrevu IS, Lofton H, Sarva K, Blasczyk E, Plocinska R, Chinnaswamy J, Madiraju M, Rajagopalan M (2011) ChiZ levels modulate cell division process in mycobacteria. Tuberculosis (Edinb) 91:S128–135

    Article  CAS  Google Scholar 

  • van der Veen S, Hain T, Wouters JA, Hossain H, de Vos WM, Abee T, Chakraborty T, Wells-Bennik MH (2007) The heat-shock response of Listeria monocytogenes comprises genes involved in heat shock, cell division, cell wall synthesis, and the SOS response. Microbiology 153:3593–3607

    Article  PubMed  CAS  Google Scholar 

  • Wang M, Fang C, Ma B, Luo X, Hou Z (2019) Regulation of cytokinesis: FtsZ and its accessory proteins. Curr Genet. https://doi.org/10.1007/s00294-019-01005-6

    Article  PubMed  Google Scholar 

  • Wu WF, Zhou Y, Gottesman S (1999) Redundant in vivo proteolytic activities of Escherichia coli Lon and the ClpYQ (HslUV) protease. J Bacteriol 181:3681–3687

    Article  CAS  PubMed  PubMed Central  Google Scholar 

Download references

Acknowledgements

The work in the authors’ lab was supported by grants from the Danish Council for Independent Research (1337-00129 and 1335-00772 to MSB) and the Danish National Research Foundation (DNRF120 to HI). We thank members of our own lab as well as members from the laboratories of Prof. Simon Foster (University of Sheffield) and Prof. Jan-Willem Veening (University of Lausanne) for encouraging discussions and collaboration.

Author information

Authors and Affiliations

  1. Department of Veterinary and Animal Sciences, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark

    Martin S. Bojer, Dorte Frees & Hanne Ingmer

Authors
  1. Martin S. Bojer
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Dorte Frees
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Hanne Ingmer
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Hanne Ingmer.

Additional information

Communicated by M. Kupiec.

Publisher's Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Bojer, M.S., Frees, D. & Ingmer, H. SosA in Staphylococci: an addition to the paradigm of membrane-localized, SOS-induced cell division inhibition in bacteria. Curr Genet 66, 495–499 (2020). https://doi.org/10.1007/s00294-019-01052-z

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00294-019-01052-z

Keywords

Search

Navigation