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The high diversity among Leptospira species provides an array to look for important mediators involved in pathogenesis. Toxin-antitoxin (TA) systems represent an important survival mechanism on stress conditions. vapBC modules have been found in nearly one thousand genomes corresponding to about 40% of known TAs. In the present study, we investigated TA profiles of some strains of Leptospira using a TA database and compared them through protein alignment of VapC toxin sequences among Leptospira spp. genomes. Our analysis identified significant differences in the number of putative vapBC modules distributed in pathogenic, saprophytic, and intermediate strains: four in L. interrogans, three in L. borgpetersenii, eight in L. biflexa, and 15 in L. licerasiae. The VapC toxins show low identity among amino acid sequences within the species. Some VapC toxins appear to be exclusively conserved in unique species, others appear to be conserved among pathogenic or saprophytic strains, and some appear to be distributed randomly. The data shown here indicate that these modules evolved in a very complex manner, which highlights the strong need to identify and characterize new TAs as well as to understand their regulation networks and the possible roles of TA systems in pathogenic bacteria.<\/jats:p>","DOI":"10.3390\/microorganisms7020056","type":"journal-article","created":{"date-parts":[[2019,2,20]],"date-time":"2019-02-20T11:45:39Z","timestamp":1550663139000},"page":"56","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["In Silico Analysis of Genetic VapC Profiles from the Toxin-Antitoxin Type II VapBC Modules among Pathogenic, Intermediate, and Non-Pathogenic Leptospira"],"prefix":"10.3390","volume":"7","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0204-3875","authenticated-orcid":false,"given":"Alexandre P. Y.","family":"Lopes","sequence":"first","affiliation":[{"name":"Laborat\u00f3rio Especial de Desenvolvimento de Vacinas\u2014Centro de Biotecnologia, Instituto Butantan, Avenida Vital Brazil, 1500, 05503-900 S\u00e3o Paulo, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Bruna O. P.","family":"Azevedo","sequence":"additional","affiliation":[{"name":"Laborat\u00f3rio Especial de Desenvolvimento de Vacinas\u2014Centro de Biotecnologia, Instituto Butantan, Avenida Vital Brazil, 1500, 05503-900 S\u00e3o Paulo, Brazil"},{"name":"Programa de P\u00f3s-Gradua\u00e7\u00e3o Interunidades em Biotecnologia, Instituto de Ci\u00eancias Biom\u00e9dicas, USP, Avenida Prof. Lineu Prestes, 1730, 05508-900 S\u00e3o Paulo, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Rebeca C.","family":"Em\u00eddio","sequence":"additional","affiliation":[{"name":"Laborat\u00f3rio Especial de Desenvolvimento de Vacinas\u2014Centro de Biotecnologia, Instituto Butantan, Avenida Vital Brazil, 1500, 05503-900 S\u00e3o Paulo, Brazil"},{"name":"Programa de P\u00f3s-Gradua\u00e7\u00e3o Interunidades em Biotecnologia, Instituto de Ci\u00eancias Biom\u00e9dicas, USP, Avenida Prof. Lineu Prestes, 1730, 05508-900 S\u00e3o Paulo, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Deborah K.","family":"Damiano","sequence":"additional","affiliation":[{"name":"Laborat\u00f3rio Especial de Desenvolvimento de Vacinas\u2014Centro de Biotecnologia, Instituto Butantan, Avenida Vital Brazil, 1500, 05503-900 S\u00e3o Paulo, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ana L. T. O.","family":"Nascimento","sequence":"additional","affiliation":[{"name":"Laborat\u00f3rio Especial de Desenvolvimento de Vacinas\u2014Centro de Biotecnologia, Instituto Butantan, Avenida Vital Brazil, 1500, 05503-900 S\u00e3o Paulo, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Giovana C.","family":"Barazzone","sequence":"additional","affiliation":[{"name":"Laborat\u00f3rio Especial de Desenvolvimento de Vacinas\u2014Centro de Biotecnologia, Instituto Butantan, Avenida Vital Brazil, 1500, 05503-900 S\u00e3o Paulo, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2019,2,20]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1265","DOI":"10.1016\/S1286-4579(00)01280-6","article-title":"Overview of the epidemiology, microbiology, and pathogenesis of Leptospira spp. in humans","volume":"2","author":"Plank","year":"2000","journal-title":"Microbes Infect."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"757","DOI":"10.1016\/S1473-3099(03)00830-2","article-title":"Leptospirosis: A zoonotic disease of global importance","volume":"3","author":"Bharti","year":"2003","journal-title":"Lancet Infect. Dis."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"296","DOI":"10.1128\/CMR.14.2.296-326.2001","article-title":"Leptospirosis","volume":"14","author":"Levett","year":"2001","journal-title":"Clin. Microbiol. Rev."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"280","DOI":"10.3390\/pathogens3020280","article-title":"Leptospiral pathogenomics","volume":"3","author":"Lehmann","year":"2014","journal-title":"Pathogens"},{"doi-asserted-by":"crossref","unstructured":"Fouts, D.E., Matthias, M.A., Adhikarla, H., Adler, B., Amorim-Santos, L., Berg, D.E., Bulach, D., Buschiazzo, A., Chang, Y.F., and Galloway, R.L. (2016). What Makes a Bacterial Species Pathogenic?:Comparative Genomic Analysis of the Genus Leptospira. PLoS Negl. Trop. Dis., 10.","key":"ref_5","DOI":"10.1371\/journal.pntd.0004403"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"371","DOI":"10.1038\/nrmicro1147","article-title":"Prokaryotic toxin-antitoxin stress response loci","volume":"3","author":"Gerdes","year":"2005","journal-title":"Nat. Rev. Microbiol."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"61","DOI":"10.1146\/annurev-genet-110410-132412","article-title":"Toxin-antitoxin systems in bacteria and archaea","volume":"45","author":"Yamaguchi","year":"2011","journal-title":"Annu. Rev. Genet."},{"doi-asserted-by":"crossref","unstructured":"Lioy, V.S., Machon, C., Tabone, M., Gonzalez-Pastor, J.E., Daugelavicius, R., Ayora, S., and Alonso, J.C. (2012). The zeta toxin induces a set of protective responses and dormancy. PLoS ONE, 7.","key":"ref_8","DOI":"10.1371\/journal.pone.0030282"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"34","DOI":"10.1016\/j.micinf.2014.10.010","article-title":"ChpK and MazF of the toxin-antitoxin modules are involved in the virulence of Leptospira interrogans during infection","volume":"17","author":"Komi","year":"2015","journal-title":"Microbes Infect."},{"doi-asserted-by":"crossref","unstructured":"Ramage, H.R., Connolly, L.E., and Cox, J.S. (2009). Comprehensive functional analysis of Mycobacterium tuberculosis toxin-antitoxin systems: Implications for pathogenesis, stress responses, and evolution. PLoS Genet., 5.","key":"ref_10","DOI":"10.1371\/journal.pgen.1000767"},{"doi-asserted-by":"crossref","unstructured":"Fern\u00e1ndez-Garc\u00eda, L., Blasco, L., Lopez, M., Bou, G., Garc\u00eda-Contreras, R., Wood, T., and Tomas, M. (2016). Toxin-Antitoxin Systems in Clinical Pathogens. Toxins, 8.","key":"ref_11","DOI":"10.3390\/toxins8070227"},{"doi-asserted-by":"crossref","unstructured":"Norton, J.P., and Mulvey, M.A. (2012). Toxin-antitoxin systems are important for niche-specific colonization and stress resistance of uropathogenic Escherichia coli. PLoS Pathog., 8.","key":"ref_12","DOI":"10.1371\/journal.ppat.1002954"},{"doi-asserted-by":"crossref","unstructured":"Ren, D., Walker, A.N., and Daines, D.A. (2012). Toxin-antitoxin loci vapBC-1 and vapXD contribute to survival and virulence in nontypeable Haemophilus influenzae. BMC Microbiol., 12.","key":"ref_13","DOI":"10.1186\/1471-2180-12-263"},{"doi-asserted-by":"crossref","unstructured":"De la Cruz, M.A., Zhao, W., Farenc, C., Gimenez, G., Raoult, D., Cambillau, C., Gorvel, J.P., and M\u00e9resse, S. (2013). A toxin-antitoxin module of Salmonella promotes virulence in mice. PLoS Pathog., 9.","key":"ref_14","DOI":"10.1371\/journal.ppat.1003827"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"4616","DOI":"10.1128\/AAC.00864-15","article-title":"Borrelia burgdorferi, the Causative Agent of Lyme Disease, Forms Drug-Tolerant Persister Cells","volume":"59","author":"Sharma","year":"2015","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"966","DOI":"10.1093\/nar\/gki201","article-title":"Toxin-antitoxin loci are highly abundant in free-living but lost from host-associated prokaryotes","volume":"33","author":"Pandey","year":"2005","journal-title":"Nucleic Acids Res."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"1479","DOI":"10.3389\/fmicb.2017.01479","article-title":"The Importance of the Expendable: Toxin-Antitoxin Genes in Plasmids and Chromosomes","volume":"8","author":"Espinosa","year":"2017","journal-title":"Front. Microbiol."},{"doi-asserted-by":"crossref","unstructured":"Kang, S.M., Kim, D.H., Jin, C., and Lee, B.J. (2018). A Systematic Overview of Type II and III Toxin-Antitoxin Systems with a Focus on Druggability. Toxins, 10.","key":"ref_18","DOI":"10.3390\/toxins10120515"},{"doi-asserted-by":"crossref","unstructured":"K\u0119dzierska, B., and Hayes, F. (2016). Emerging Roles of Toxin-Antitoxin Modules in Bacterial Pathogenesis. Molecules, 21.","key":"ref_19","DOI":"10.3390\/molecules21060790"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"103","DOI":"10.1146\/annurev-micro-092611-150159","article-title":"Bacterial Persistence and Toxin-Antitoxin Loci","volume":"66","author":"Gerdes","year":"2012","journal-title":"Annu. Rev. Microbiol."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"931","DOI":"10.1099\/mic.0.000487","article-title":"Endoribonuclease type II toxin-antitoxin systems: Functional or selfish?","volume":"163","author":"Ramisetty","year":"2017","journal-title":"Microbiology"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"D606","DOI":"10.1093\/nar\/gkq908","article-title":"TADB: A web-based resource for Type 2 toxin-antitoxin loci in bacteria and archaea","volume":"39","author":"Shao","year":"2011","journal-title":"Nucleic Acids Res."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"D749","DOI":"10.1093\/nar\/gkx1033","article-title":"TADB 2.0: An updated database of bacterial type II toxin-antitoxin loci","volume":"46","author":"Xie","year":"2018","journal-title":"Nucleic Acids Res."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"913","DOI":"10.1016\/S1097-2765(03)00402-7","article-title":"MazF cleaves cellular mRNAs specifically at ACA to block protein synthesis in Escherichia coli","volume":"12","author":"Zhang","year":"2003","journal-title":"Mol. Cell"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"131","DOI":"10.1016\/S0092-8674(02)01248-5","article-title":"The bacterial toxin RelE displays codon-specific cleavage of mRNAs in the ribosomal A site","volume":"112","author":"Pedersen","year":"2003","journal-title":"Cell"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"1191","DOI":"10.1128\/JB.01013-08","article-title":"HicA of Escherichia coli defines a novel family of translation-independent mRNA interferases in bacteria and archaea","volume":"191","author":"Pandey","year":"2009","journal-title":"J. Bacteriol."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"8501","DOI":"10.1073\/pnas.1222031110","article-title":"Mycobacterial toxin MazF-mt6 inhibits translation through cleavage of 23S rRNA at the ribosomal A site","volume":"110","author":"Schifano","year":"2013","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"1256","DOI":"10.1093\/nar\/gkv1370","article-title":"tRNA is a new target for cleavage by a MazF toxin","volume":"44","author":"Schifano","year":"2016","journal-title":"Nucleic Acids Res."},{"doi-asserted-by":"crossref","unstructured":"Lopes, A.P.Y., Lopes, L.M., Fraga, T.R., Chura-Chambi, R.M., Sanson, A.L., Cheng, E., Nakajima, E., Morganti, L., and Martins, E.A.L. (2014). VapC from the Leptospiral VapBC Toxin-Antitoxin Module Displays Ribonuclease Activity on the Initiator tRNA. PLoS ONE, 9.","key":"ref_29","DOI":"10.1371\/journal.pone.0101678"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"7403","DOI":"10.1073\/pnas.1019587108","article-title":"Enteric virulence associated protein VapC inhibits translation by cleavage of initiator tRNA","volume":"108","author":"Winther","year":"2011","journal-title":"Proc. Natl. Acad. Sci. USA"},{"doi-asserted-by":"crossref","unstructured":"Walling, L.R., and Butler, J.S. (2018). Homologous VapC Toxins Inhibit Translation and Cell Growth by Sequence-Specific Cleavage of tRNA. J. Bacteriol., 200.","key":"ref_31","DOI":"10.1128\/JB.00582-17"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"9860","DOI":"10.1093\/nar\/gkw781","article-title":"VapCs of Mycobacterium tuberculosis cleave RNAs essential for translation","volume":"44","author":"Winther","year":"2016","journal-title":"Nucleic Acids Res."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"2796","DOI":"10.1038\/ncomms3796","article-title":"VapC20 of Mycobacterium tuberculosis cleaves the Sarcin-Ricin loop of 23S rRNA","volume":"4","author":"Winther","year":"2013","journal-title":"Nat. Commun."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"400","DOI":"10.1002\/prca.200600805","article-title":"Application of immunoproteomics to leptospirosis: Towards clinical diagnostics and vaccine discovery","volume":"1","author":"Kositanont","year":"2007","journal-title":"Proteom. Clin. Appl."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"459","DOI":"10.1590\/S0100-879X2004000400003","article-title":"Genome features of Leptospira interrogans serovar Copenhageni","volume":"37","author":"Nascimento","year":"2004","journal-title":"Braz. J. Med. Biol. Res."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"73","DOI":"10.1016\/j.vetmic.2011.02.055","article-title":"Pathogenesis of leptospirosis: The influence of genomics","volume":"153","author":"Adler","year":"2011","journal-title":"Vet. Microbiol."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"888","DOI":"10.1038\/nature01597","article-title":"Unique physiological and pathogenic features of Leptospira interrogans revealed by whole-genome sequencing","volume":"422","author":"Ren","year":"2003","journal-title":"Nature"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"305","DOI":"10.1016\/j.femsle.2005.02.004","article-title":"Whole-genome analysis of Leptospira interrogans to identify potential vaccine candidates against leptospirosis","volume":"244","author":"Gamberini","year":"2005","journal-title":"FEMS Microbiol. Lett."},{"doi-asserted-by":"crossref","unstructured":"Ricaldi, J.N., Fouts, D.E., Selengut, J.D., Harkins, D.M., Patra, K.P., Moreno, A., Lehmann, J.S., Purushe, J., Sanka, R., and Torres, M. (2012). Whole genome analysis of Leptospira licerasiae provides insight into leptospiral evolution and pathogenicity. PLoS Negl. Trop. Dis., 6.","key":"ref_39","DOI":"10.1371\/journal.pntd.0001853"},{"doi-asserted-by":"crossref","unstructured":"Llanes, A., Restrepo, C.M., and Rajeev, S. (2016). Whole Genome Sequencing Allows Better Understanding of the Evolutionary History of Leptospira interrogans Serovar Hardjo. PLoS ONE, 11.","key":"ref_40","DOI":"10.1371\/journal.pone.0159387"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"80","DOI":"10.1016\/j.jprot.2018.02.025","article-title":"Proteomics as a tool to understand Leptospira physiology and virulence: Recent advances, challenges and clinical implications","volume":"180","author":"Vieira","year":"2018","journal-title":"J. Proteom."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"14560","DOI":"10.1073\/pnas.0603979103","article-title":"Genome reduction in Leptospira borgpetersenii reflects limited transmission potential","volume":"103","author":"Bulach","year":"2006","journal-title":"Proc. Natl. Acad. Sci. USA"},{"doi-asserted-by":"crossref","unstructured":"Picardeau, M., Bulach, D.M., Bouchier, C., Zuerner, R.L., Zidane, N., Wilson, P.J., Creno, S., Kuczek, E.S., Bommezzadri, S., and Davis, J.C. (2008). Genome sequence of the saprophyte Leptospira biflexa provides insights into the evolution of Leptospira and the pathogenesis of leptospirosis. PLoS ONE, 3.","key":"ref_43","DOI":"10.1371\/journal.pone.0001607"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"2164","DOI":"10.1128\/JB.186.7.2164-2172.2004","article-title":"Comparative genomics of two Leptospira interrogans serovars reveals novel insights into physiology and pathogenesis","volume":"186","author":"Nascimento","year":"2004","journal-title":"J. Bacteriol."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"33","DOI":"10.1093\/protein\/gzq081","article-title":"The PIN-domain ribonucleases and the prokaryotic VapBC toxin-antitoxin array","volume":"24","author":"Arcus","year":"2011","journal-title":"Protein Eng. Des. Sel."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"208","DOI":"10.1038\/sj.cr.7290221","article-title":"Characterization of a novel toxin-antitoxin module, VapBC, encoded by Leptospira interrogans chromosome","volume":"14","author":"Zhang","year":"2004","journal-title":"Cell Res."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"277","DOI":"10.1016\/S0378-1097(03)00848-6","article-title":"The spirochetal chpK-chromosomal toxin-antitoxin locus induces growth inhibition of yeast and mycobacteria","volume":"229","author":"Picardeau","year":"2003","journal-title":"FEMS Microbiol. Lett."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"561","DOI":"10.1128\/JB.182.3.561-572.2000","article-title":"Toxin-antitoxin modules may regulate synthesis of macromolecules during nutritional stress","volume":"182","author":"Gerdes","year":"2000","journal-title":"J. Bacteriol."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"6850","DOI":"10.1128\/jb.175.21.6850-6856.1993","article-title":"chpA and chpB, Escherichia coli chromosomal homologs of the pem locus responsible for stable maintenance of plasmid R100","volume":"175","author":"Masuda","year":"1993","journal-title":"J. Bacteriol."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"768","DOI":"10.1016\/j.molcel.2018.01.003","article-title":"Toxins, Targets, and Triggers: An Overview of Toxin-Antitoxin Biology","volume":"70","author":"Harms","year":"2018","journal-title":"Mol. Cell"},{"doi-asserted-by":"crossref","unstructured":"Sierra, R., Viollier, P., and Renzoni, A. (2018). Linking toxin-antitoxin systems with phenotypes: A Staphylococcus aureus viewpoint. Biochim. Biophys. Acta Gene Regul. Mech.","key":"ref_51","DOI":"10.1016\/j.bbagrm.2018.07.009"},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"4347","DOI":"10.1093\/nar\/gks029","article-title":"Regulation of Enteric vapBC Transcription: Induction by VapC Toxin Dimer-Breaking","volume":"40","author":"Winther","year":"2012","journal-title":"Nucleic Acids Res."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"9374","DOI":"10.1038\/srep09374","article-title":"Distinct type I and type II toxin-antitoxin modules control Salmonella lifestyle inside eukaryotic cells","volume":"5","author":"Figueroa","year":"2015","journal-title":"Sci. Rep."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"123","DOI":"10.1042\/BST0370123","article-title":"Role of vapBC toxin-antitoxin loci in the thermal stress response of Sulfolobus solfataricus","volume":"37","author":"Cooper","year":"2009","journal-title":"Biochem. Soc. Trans."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"133","DOI":"10.1007\/s00294-018-0879-8","article-title":"Autoregulation of bacterial gene expression: Lessons from the MazEF toxin-antitoxin system","volume":"65","author":"Nikolic","year":"2019","journal-title":"Curr. Genet."},{"doi-asserted-by":"crossref","unstructured":"Victoria, B., Ahmed, A., Zuerner, R.L., Ahmed, N., Bulach, D.M., Quinteiro, J., and Hartskeerl, R.A. (2008). Conservation of the S10-spc-alpha locus within otherwise highly plastic genomes provides phylogenetic insight into the genus Leptospira. PLoS ONE, 3.","key":"ref_56","DOI":"10.1371\/journal.pone.0002752"},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"677","DOI":"10.3389\/fmicb.2014.00677","article-title":"Functional validation of putative toxin-antitoxin genes from the Gram-positive pathogen Streptococcus pneumoniae: Phd-doc is the fourth bona-fide operon","volume":"5","author":"Chan","year":"2014","journal-title":"Front. Microbiol."},{"doi-asserted-by":"crossref","unstructured":"Ahidjo, B.A., Kuhnert, D., McKenzie, J.L., Machowski, E.E., Gordhan, B.G., Arcus, V., Abrahams, G.L., and Mizrahi, V. (2011). VapC toxins from Mycobacterium tuberculosis are ribonucleases that differentially inhibit growth and are neutralized by cognate VapB antitoxins. PLoS ONE, 6.","key":"ref_58","DOI":"10.1371\/journal.pone.0021738"},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"762","DOI":"10.1038\/nature08184","article-title":"Proteome-wide cellular protein concentrations of the human pathogen Leptospira interrogans","volume":"460","author":"Beck","year":"2009","journal-title":"Nature"},{"doi-asserted-by":"crossref","unstructured":"Ramisetty, B.C., and Santhosh, R.S. (2016). Horizontal gene transfer of chromosomal Type II toxin-antitoxin systems of Escherichia coli. FEMS Microbiol. Lett., 363.","key":"ref_60","DOI":"10.1093\/femsle\/fnv238"},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"158","DOI":"10.1099\/mic.0.082883-0","article-title":"Type II toxin-antitoxin systems are unevenly distributed among Escherichia coli phylogroups","volume":"161","author":"Fiedoruk","year":"2015","journal-title":"Microbiology"}],"container-title":["Microorganisms"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2076-2607\/7\/2\/56\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T12:33:35Z","timestamp":1760186015000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2076-2607\/7\/2\/56"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2019,2,20]]},"references-count":61,"journal-issue":{"issue":"2","published-online":{"date-parts":[[2019,2]]}},"alternative-id":["microorganisms7020056"],"URL":"https:\/\/doi.org\/10.3390\/microorganisms7020056","relation":{},"ISSN":["2076-2607"],"issn-type":[{"type":"electronic","value":"2076-2607"}],"subject":[],"published":{"date-parts":[[2019,2,20]]}}}