Skip to main content
SpringerLink
Log in

Orthocaspase and toxin-antitoxin loci rubbing shoulders in the genome of Microcystis aeruginosa PCC 7806

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

Abstract

Programmed cell death in multicellular organisms is a coordinated and precisely regulated process. On the other hand, in bacteria we have little clue about the network of interacting molecules that result in the death of a single cell within a population or the death of almost complete population, such as often observed in cyanobacterial blooms. With the recent discovery that orthocaspase MaOC1 of the cyanobacterium Microcystis aeruginosa is an active proteolytic enzyme, we have gained a possible hint about at least one step in the process, but the picture is far from complete. Interestingly, the genomic context of MaOC1 revealed the presence of multiple copies of genes that belong to toxin–antitoxin modules. It has been speculated that these also play a role in bacterial programmed cell death. The discovery of two components linked to cell death within the same genomic region could open new ways to deciphering the underlying mechanisms of cyanobacterial cell death.

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

  • Allocati N, Masulli M, Di Ilio C, De Laurenzi V (2015) Die for the community: an overview of programmed cell death in bacteria. Cell Death Dis 6:e1609

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Amitai S, Yassin Y, Engelberg-Kulka H (2004) MazF-mediated cell death in Escherichia coli: a point of no return. J Bacteriol 186:8295–8300

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Aravind L, Koonin EV (2002) Classification of the caspase-hemoglobinase fold: detection of new families and implications for the origin of the eukaryotic separins. Proteins 46:355–367

    Article  CAS  PubMed  Google Scholar 

  • Asplund-Samuelsson J (2015) The art of destruction: revealing the proteolytic capacity of bacterial caspase homologs. Mol Microbiol 98:1–6

    Article  CAS  PubMed  Google Scholar 

  • Bar-Zeev E, Avishay I, Bidle KD, Berman-Frank I (2013) Programmed cell death in the marine cyanobacterium Trichodesmium mediates carbon and nitrogen export. ISME J 7:2340–2348

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Bayles KW (2014) Bacterial programmed cell death: making sense of a paradox. Nat Rev Microbiol 12:63–69

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Berman-Frank I, Bidle KD, Haramati L, Falkowski P (2004) The demise of the marine cyanobacterium, Trichodesmium spp., via an autocatalysed cell death pathway. Limnol Oceanogr 49:997–1005

    Article  Google Scholar 

  • Boratyn GM, Schaffer AA, Agarwala R, Altschul SF, Lipman DJ, Madden TL (2012) Domain enhanced lookup time accelerated BLAST. Biol Dir 7:12

    Article  CAS  Google Scholar 

  • Brantl S (2012) Bacterial type I toxin–antitoxin systems. RNA Biol 9:1488–1490

    Article  CAS  PubMed  Google Scholar 

  • Brantl S, Jahn N (2015) sRNAs in bacterial type I and type III toxin–antitoxin systems. FEMS Microbiol Rev 39:413–427

    Article  PubMed  Google Scholar 

  • Dawson RM (1998) The toxicology of microcystins. Toxicon 36:953–962

    Article  CAS  PubMed  Google Scholar 

  • Ding Y, Gan N, Li J, Sedmak B, Song L (2012) Hydrogen peroxide induces apoptotic-like cell death in Microcystis aeruginosa (Chroococcales, Cyanobacteria) in a dose-dependent manner. Phycologia 51:567–575

    Article  CAS  Google Scholar 

  • Donegan NP, Thompson ET, Fu Z, Cheung AL (2010) Proteolytic regulation of toxin–antitoxin systems by ClpPC in Staphylococcus aureus. J Bacteriol 192:1416–1422

    Article  CAS  PubMed  Google Scholar 

  • Engelberg-Kulka H, Amitai S, Kolodkin-Gal I, Hazan R (2006) Bacterial programmed cell death and multicellular behavior in bacteria. PLoS Genet 2:e135

    Article  PubMed  PubMed Central  Google Scholar 

  • Erental A, Sharon I, Engelberg-Kulka H (2012) Two programmed cell death systems in Escherichia coli: an apoptotic-like death is inhibited by the mazEF-mediated death pathway. PLoS Biol 10:e1001281

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Frangeul L, Quillardet P, Castets AM, Humbert JF, Matthijs HC, Cortez D, Tolonen A, Zhang CC, Gribaldo S, Kehr JC, Zilliges Y, Ziemert N, Becker S, Talla E, Latifi A, Billault A, Lepelletier A, Dittmann E, Bouchier C, de Marsac NT (2008) Highly plastic genome of Microcystis aeruginosa PCC 7806, a ubiquitous toxic freshwater cyanobacterium. BMC Genom 9:274

    Article  Google Scholar 

  • Galluzzi L, Vitale I, Abrams JM, Alnemri ES, Baehrecke EH, Blagosklonny MV, Dawson TM, Dawson VL, El-Deiry WS, Fulda S, Gottlieb E, Green DR, Hengartner MO, Kepp O, Knight RA, Kumar S, Lipton SA, Lu X, Madeo F, Malorni W, Mehlen P, Nunez G, Peter ME, Piacentini M, Rubinsztein DC, Shi Y, Simon HU, Vandenabeele P, White E, Yuan J, Zhivotovsky B, Melino G, Kroemer G (2012) Molecular definitions of cell death subroutines: recommendations of the Nomenclature Committee on Cell Death 2012. Cell Death Differ 19:107–120

    Article  CAS  PubMed  Google Scholar 

  • Gotfredsen M, Gerdes K (1998) The Escherichia coli relBE genes belong to a new toxin–antitoxin gene family. Mol Microbiol 29:1065–1076

    Article  CAS  PubMed  Google Scholar 

  • Hachmann J, Snipas SJ, van Raam BJ, Cancino EM, Houlihan EJ, Poreba M, Kasperkiewicz P, Drag M, Salvesen GS (2012) Mechanism and specificity of the human paracaspase MALT1. Biochem J 443:287–295

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Humbert JF, Barbe V, Latifi A, Gugger M, Calteau A, Coursin T, Lajus A, Castelli V, Oztas S, Samson G, Longin C, Medigue C, de Marsac NT (2013) A tribute to disorder in the genome of the bloom-forming freshwater cyanobacterium Microcystis aeruginosa. PLoS ONE 8:e70747

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Jiang Q, Qin S, Wu QY (2010) Genome-wide comparative analysis of metacaspases in unicellular and filamentous cyanobacteria. BMC Genom 11:198

    Article  Google Scholar 

  • Klemenčič M, Novinec M, Dolinar M (2015) Orthocaspases are proteolytically active prokaryotic caspase homologues: the case of Microcystis aeruginosa. Mol Microbiol 98:142–150

    Article  PubMed  Google Scholar 

  • Masuda H, Tan Q, Awano N, Wu KP, Inouye M (2012) YeeU enhances the bundling of cytoskeletal polymers of MreB and FtsZ, antagonizing the CbtA (YeeV) toxicity in Escherichia coli. Mol Microbiol 84:979–989

    Article  CAS  PubMed  Google Scholar 

  • Mruk I, Kobayashi I (2014) To be or not to be: regulation of restriction-modification systems and other toxin–antitoxin systems. Nucleic Acids Res 42:70–86

    Article  CAS  PubMed  Google Scholar 

  • Nedelcu AM, Driscoll WW, Durand PM, Herron MD, Rashidi A (2011) On the paradigm of altruistic suicide in the unicellular world. Evolution 65:3–20

    Article  PubMed  Google Scholar 

  • Ning SB, Guo HL, Wang L, Song YC (2002) Salt stress induces programmed cell death in prokaryotic organism Anabaena. J Appl Microbiol 93:15–28

    Article  CAS  PubMed  Google Scholar 

  • Ning D, Liu S, Xu W, Zhuang Q, Wen C, Tang X (2013) Transcriptional and proteolytic regulation of the toxin–antitoxin locus vapBC10 (ssr2962/slr1767) on the chromosome of Synechocystis sp. PCC 6803. PLoS ONE 8:e80716

    Article  PubMed  PubMed Central  Google Scholar 

  • Otsuka S (2016) Prokaryotic toxin–antitoxin systems: novel regulations of the toxins. Curr Genet. doi:10.1007/s00294-015-0557-z

  • Otsuka S, Suda S, Li R, Matsumoto S, Watanabe MM (2000) Morphological variability of colonies of Microcystis morphospecies in culture. J Genl Appl Microbiol 46:39–50

    Article  CAS  Google Scholar 

  • Paerl HW, Fulton RS 3rd, Moisander PH, Dyble J (2001) Harmful freshwater algal blooms, with an emphasis on cyanobacteria. Sci World J 1:76–113

    Article  CAS  Google Scholar 

  • Pandey DP, Gerdes K (2005) Toxin–antitoxin loci are highly abundant in free-living but lost from host-associated prokaryotes. Nucleic Acids Res 33:966–976

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Pedersen K, Christensen SK, Gerdes K (2002) Rapid induction and reversal of a bacteriostatic condition by controlled expression of toxins and antitoxins. Mol Microbiol 45:501–510

    Article  CAS  PubMed  Google Scholar 

  • Rocker A, Meinhart A (2015) Type II toxin: antitoxin systems. More than small selfish entities? Curr Genet. doi:10.1007/s00294-015-0541-7

  • Ross C, Santiago-Vazquez L, Paul V (2006) Toxin release in response to oxidative stress and programmed cell death in the cyanobacterium Microcystis aeruginosa. Aquat Toxicol 78:66–73

    Article  CAS  PubMed  Google Scholar 

  • Sabart M, Pobel D, Latour D, Robin J, Salencon MJ, Humbert JF (2009) Spatiotemporal changes in the genetic diversity in French bloom-forming populations of the toxic cyanobacterium, Microcystis aeruginosa. Environ Microbiol Rep 1:263–272

    Article  CAS  PubMed  Google Scholar 

  • Schuster CF, Bertram R (2013) Toxin–antitoxin systems are ubiquitous and versatile modulators of prokaryotic cell fate. FEMS Microbiol Lett 340:73–85

    Article  CAS  PubMed  Google Scholar 

  • Shemarova IV (2010) Signaling mechanisms of apoptosis-like programmed cell death in unicellular eukaryotes. Comp Biochem Physiol Part B 155:341–353

    Article  Google Scholar 

  • Sigee DC, Selwyn A, Gallois P, Dean AP (2007) Patterns of cell death in freshwater colonial cyanobacteria during the late summer bloom. Phycologia 46:284–292

    Article  Google Scholar 

  • Tanouchi Y, Pai A, Buchler NE, You L (2012) Programming stress-induced altruistic death in engineered bacteria. Mol Syst Biol 8:626

    Article  PubMed  PubMed Central  Google Scholar 

  • Uren AG, O’Rourke K, Aravind LA, Pisabarro MT, Seshagiri S, Koonin EV, Dixit VM (2000) Identification of paracaspases and metacaspases: two ancient families of caspase-like proteins, one of which plays a key role in MALT lymphoma. Mol Cell 6:961–967

    CAS  PubMed  Google Scholar 

  • van Gremberghe I, Leliaert F, Mergeay J, Vanormelingen P, Van der Gucht K, Debeer AE, Lacerot G, De Meester L, Vyverman W (2011) Lack of phylogeographic structure in the freshwater cyanobacterium Microcystis aeruginosa suggests global dispersal. PLoS ONE 6:e19561

    Article  PubMed  PubMed Central  Google Scholar 

  • Van Melderen L, Saavedra De Bast M (2009) Bacterial toxin–antitoxin systems: more than selfish entities? PLoS Genetics 5:e1000437

    Article  PubMed  PubMed Central  Google Scholar 

  • Vercammen D, van de Cotte B, De Jaeger G, Eeckhout D, Casteels P, Vandepoele K, Vandenberghe I, Van Beeumen J, Inze D, Van Breusegem F (2004) Type II metacaspases Atmc4 and Atmc9 of Arabidopsis thaliana cleave substrates after arginine and lysine. J Biol Chem 279:45329–45336

    Article  CAS  PubMed  Google Scholar 

  • Wang X, Lord DM, Cheng HY, Osbourne DO, Hong SH, Sanchez-Torres V, Quiroga C, Zheng K, Herrmann T, Peti W, Benedik MJ, Page R, Wood TK (2012) A new type V toxin–antitoxin system where mRNA for toxin GhoT is cleaved by antitoxin GhoS. Nat Chem Biol 8:855–861

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Wang Y, Wang H, Hay AJ, Zhong Z, Zhu J, Kan B (2015) Functional RelBE-family toxin–antitoxin pairs affect biofilm maturation and intestine colonization in Vibrio cholerae. PLoS ONE 10:e0135696

    Article  PubMed  PubMed Central  Google Scholar 

  • Watanabe N, Lam E (2005) Two Arabidopsis metacaspases AtMCP1b and AtMCP2b are arginine/lysine-specific cysteine proteases and activate apoptosis-like cell death in yeast. J Biol Chem 280:14691–14699

    Article  CAS  PubMed  Google Scholar 

  • Wegener KM, Singh AK, Jacobs JM, Elvitigala T, Welsh EA, Keren N, Gritsenko MA, Ghosh BK, Camp DG 2nd, Smith RD, Pakrasi HB (2010) Global proteomics reveal an atypical strategy for carbon/nitrogen assimilation by a cyanobacterium under diverse environmental perturbations. Mol Cell Proteom 9:2678–2689

    Article  CAS  Google Scholar 

  • Yamaguchi Y, Park JH, Inouye M (2011) Toxin–antitoxin systems in bacteria and archaea. Annu Rev Genet 45:61–79

    Article  CAS  PubMed  Google Scholar 

  • Yang C, Lin F, Li Q, Li T, Zhao J (2015) Comparative genomics reveals diversified CRISPR-Cas systems of globally distributed Microcystis aeruginosa, a freshwater bloom-forming cyanobacterium. Front Microbiol 6:394

    PubMed  PubMed Central  Google Scholar 

  • Zhai C, Zhang P, Shen F, Zhou C, Liu C (2012) Does Microcystis aeruginosa have quorum sensing? FEMS Microbiol Lett 336:38–44

    Article  CAS  PubMed  Google Scholar 

  • Zhang YX, Li J, Guo XK, Wu C, Bi B, Ren SX, Wu CF, Zhao GP (2004) Characterization of a novel toxin–antitoxin module, VapBC, encoded by Leptospira interrogans chromosome. Cell Res 14:208–216

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgments

For a part of this project we have received funding from the European Union’s Seventh Programme for research, technological development and demonstration under Grant agreement No. 308518, CyanoFactory.

Author information

Authors and Affiliations

  1. Department of Chemistry and Biochemistry, Faculty of Chemistry and Chemical Technology, University of Ljubljana, Večna pot 113, 1000, Ljubljana, Slovenia

    Marina Klemenčič & Marko Dolinar

Authors
  1. Marina Klemenčič
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Marko Dolinar
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Marko Dolinar.

Additional information

Communicated by M. Kupiec.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Klemenčič, M., Dolinar, M. Orthocaspase and toxin-antitoxin loci rubbing shoulders in the genome of Microcystis aeruginosa PCC 7806. Curr Genet 62, 669–675 (2016). https://doi.org/10.1007/s00294-016-0582-6

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00294-016-0582-6

Keywords

Search

Navigation