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Whole-Genome Sequence Analysis of Paenibacillus alvei JR949 Revealed Biosynthetic Gene Clusters Coding for Novel Antimicrobials

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Abstract

The increased prevalence of multidrug-resistant pathogens poses a significant clinical threat, and hence, the discovery of novel antibiotics is the need of the hour. Several attempts are being made worldwide to screen and identify newer antibiotics from various microbial sources. The genus Paenibacillus is known for its biosynthetic potential and metabolic versatility in producing several secondary metabolites. In this study, we isolated Paenibacillus alvei strain JR949 from the soil, which exhibited antimicrobial activity against Enteropathogenic Escherichia coli (EPEC), Pseudomonas aeruginosa (PAO1), and methicillin-resistant Staphylococcus aureus (MRSA). The whole genome of this strain was sequenced using the Illumina platform. The genome mining of the draft genome sequence revealed a total of 31 biological gene clusters (BGCs) responsible for the synthesis of secondary metabolites. The construction of the similarity network of the BGCs and the comparative analysis with the genetically related strains aided the identification of metabolites produced by this strain. We identified BGCs coding for paenibactin, paenibacterin, anabaenopeptin NZ857, icosalide A/B, polymyxin, and bicornutinA1/A2 with 100% similarity. The BGCs with lower sequence similarity to paenibacterin, polymyxin B, colistin A/B, pellasoren, tridecaptin, pelgipeptin, and marthiapeptide were also identified. Furthermore, 13 putative NRPS BGCs, 3 NRPS-T1PKS hybrid clusters, a T1PKS, and a bacteriocin BGC were identified with very low similarity (≤ 25%) or no similarity with known antibiotics. Further experimental investigations may result in the discovery of novel antimicrobial drugs.

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source genomes and the node shapes indicate the biosynthetic classes

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References

  1. O’neill J (2016) Review on antimicrobial resistance: tackling a crisis for the health and wealth of nations, 2014. HM Government, London

    Google Scholar 

  2. World Health Organization (2001) WHO global strategy for containment of antimicrobial resistance (No. WHO/CDS/CSR/DRS/2001.2). World Health Organization, Geneva

    Google Scholar 

  3. Priest FG, Goodfellow M, Todd C (1988) A numerical classification of the genus Bacillus. J Gen Microbiol 134:1847–1882. https://doi.org/10.1099/00221287-134-7-1847

    Article  CAS  PubMed  Google Scholar 

  4. Grady EN, MacDonald J, Liu L, Richman A, Yuan ZC (2016) Current knowledge and perspectives of Paenibacillus: a review. Microb Cell Fact 15:203. https://doi.org/10.1186/s12934-016-0603-7

    Article  PubMed  PubMed Central  Google Scholar 

  5. Cochrane SA, Vederas JC (2016) Lipopeptides from Bacillus and Paenibacillus spp.: a gold mine of antibiotic candidates. Med Res Rev 36:4–31. https://doi.org/10.1002/med.21321

    Article  CAS  PubMed  Google Scholar 

  6. He Z, Kisla D, Zhang L, Yuan C, Green-Church KB, Yousef AE (2007) Isolation and identification of a Paenibacillus polymyxa strain that coproduces a novel lantibiotic and polymyxin. Appl Environ Microb 73:168–178. https://doi.org/10.1128/AEM.02023-06

    Article  CAS  Google Scholar 

  7. Bankevich A, Nurk S, Antipov D, Gurevich AA, Dvorkin M et al (2012) SPAdes: a new genome assembly algorithm and its applications to single-cell sequencing. J Comput Biol 19:455–477. https://doi.org/10.1089/cmb.2012.0021

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  8. Jolley KA, Bliss CM, Bennett JS, Bratcher HB, Brehony C et al (2012) Ribosomal multilocus sequence ty**: universal characterization of bacteria from domain to strain. Microbiology (Reading) 158:1005–1015. https://doi.org/10.1099/mic.0.055459-0

    Article  CAS  Google Scholar 

  9. Meier-Kolthoff JP, Auch AF, Klenk HP, Göker M (2013) Genome sequence-based species delimitation with confidence intervals and improved distance functions. BMC Bioinform 14:60. https://doi.org/10.1186/1471-2105-14-60

    Article  Google Scholar 

  10. Vallenet D, Calteau A, Dubois M, Amours P, Bazin A et al (2020) MicroScope: an integrated platform for the annotation and exploration of microbial gene functions through genomic, pangenomic and metabolic comparative analysis. Nucleic Acids Res 48:579–589. https://doi.org/10.1093/nar/gkz926

    Article  CAS  Google Scholar 

  11. Zhang H, Yohe T, Huang L, Entwistle S, Wu P et al (2018) dbCAN2: a meta server for automated carbohydrate-active enzyme annotation. Nucleic Acids Res 46:95–101. https://doi.org/10.1093/nar/gky418

    Article  CAS  Google Scholar 

  12. Blin K, Shaw S, Steinke K, Villebro R, Ziemert N et al (2019) antiSMASH 5.0: updates to the secondary metabolite genome mining pipeline. Nucleic Acids Res 47:81–87. https://doi.org/10.1093/nar/gkz310

    Article  CAS  Google Scholar 

  13. Anand S, Prasad MVR, Yadav G, Kumar N, Shehara J et al (2010) SBSPKS: structure based sequence analysis of polyketide synthases. Nucleic Acids Res 38:487–496. https://doi.org/10.1093/nar/gkq340

    Article  CAS  Google Scholar 

  14. Kautsar SA, Blin K, Shaw S, Navarro-Muñoz JC, Terlouw BR et al (2020) MIBiG 2.0: a repository for biosynthetic gene clusters of known function. Nucleic Acids Res 48:454–458. https://doi.org/10.1093/nar/gkz882

    Article  Google Scholar 

  15. Navarro-Muñoz JC, Selem-Mojica N, Mullowney MW, Kautsar SA, Tryon JH et al (2020) A computational framework to explore large-scale biosynthetic diversity. Nat Chem Biol 16:60–68. https://doi.org/10.1038/s41589-019-0400-9

    Article  CAS  PubMed  Google Scholar 

  16. Gu Z, Gu L, Eils R, Schlesner M, Brors B (2014) Circlize implements and enhances circular visualization in R. Bioinformatics 30:2811–2812. https://doi.org/10.1093/bioinformatics/btu393

    Article  CAS  PubMed  Google Scholar 

  17. Csizmadia P (1999) Marvinsketch and marvinview: molecule applets for the world wide web. http://www.chemaxon.com

  18. Bionda N, Pitteloud JP, Cudic P (2013) Cyclic lipodepsipeptides: a new class of antibacterial agents in the battle against resistant bacteria. Future Med Chem 5:1311–1330. https://doi.org/10.4155/fmc.13.86

    Article  CAS  PubMed  Google Scholar 

  19. Huang E, Yousef AE (2014) Paenibacterin, a novel broad-spectrum lipopeptide antibiotic, neutralises endotoxins and promotes survival in a murine model of Pseudomonas aeruginosa-induced sepsis. Int J Antimicrob Agents 44:74–77. https://doi.org/10.1016/j.ijantimicag.2014.02.018

    Article  CAS  PubMed  Google Scholar 

  20. Olishevska S, Nickzad A, Déziel E (2019) Bacillus and Paenibacillus secreted polyketides and peptides involved in controlling human and plant pathogens. Appl Microbiol Biotechnol 103:1189–1215. https://doi.org/10.1007/s00253-018-9541-0

    Article  CAS  PubMed  Google Scholar 

  21. Li J, Nation RL, Turnidge JD, Milne RW, Coulthard K et al (2006) Colistin: the re emerging antibiotic for multidrug-resistant gram-negative bacterial infections. Lancet Infect Dis 6:589–601. https://doi.org/10.1016/S1473-3099(06)70580-1

    Article  CAS  PubMed  Google Scholar 

  22. Qian CD, Liu TZ, Zhou SL, Ding R, Zhao WP et al (2012) Identification and functional analysis of gene cluster involvement in biosynthesis of the cyclic lipopeptide antibiotic pelgipeptin produced by Paenibacillus elgii. BMC Microbiol 12:197. https://doi.org/10.1186/1471-2180-12-197

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  23. Jangra M, Kaur M, Tambat R, Rana R, Maurya SK et al (2019) Tridecaptin M, a new variant discovered in mud bacterium, shows activity against colistin- and extremely drug-resistant Enterobacteriaceae. Antimicrob Agents Chemother 63:e00338-e419. https://doi.org/10.1128/AAC.00338-19

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  24. Zhou X, Huang H, Chen Y, Tan J, Song Y et al (2012) Marthiapeptide A, an anti-infective and cytotoxic polythiazole cyclopeptide from a 60 L scale fermentation of the deep sea-derived Marinactinospora thermotolerans SCSIO 00652. J Nat Prod 75:2251–2255. https://doi.org/10.1021/np300554f

    Article  CAS  PubMed  Google Scholar 

  25. Boros C, Smith CJ, Vasina Y, Che Y, Dix AB et al (2006) Isolation and Identification of the Icosalides-cyclic peptolides with selective antibiotic and cytotoxic activities. J Antibiot 59:486–494. https://doi.org/10.1038/ja.2006.68

    Article  CAS  Google Scholar 

  26. Johnson BA, Anker H, Meleney FL (1945) Bacitracin: a new antibiotic produced by a member of the Bacillus subtilis group. Science 102:376–377. https://doi.org/10.1126/science.102.2650.376

    Article  CAS  PubMed  Google Scholar 

  27. Swierstra J, Kapoerchan V, Knijnenburg A, van Belkum A, Overhand M (2016) Structure, toxicity and antibiotic activity of gramicidin S and derivatives. Eur J Clin Microbiol 35:763–769. https://doi.org/10.1007/s10096-016-2595-y

    Article  CAS  Google Scholar 

  28. Wenzel M, Rautenbach M, Vosloo JA, Siersma T, Aisenbrey CHM et al (2018) The multifaceted antibacterial mechanisms of the pioneering peptide antibiotics tyrocidine and gramicidin S. mBio. https://doi.org/10.1128/mBio.00802-18

    Article  PubMed  PubMed Central  Google Scholar 

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Acknowledgements

The authors acknowledge the UGC-NRCBS, DBT-IPLS, DST-PURSE, and DST-FIIST Programs of the School of Biological Sciences, Madurai Kamaraj University.

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Madurai Kamaraj University.

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JR, RS, and RK: designed the experiments. PSP, BM, RS: performed experiments. PSP and JR: wrote the experiment. All authors read and approved the final manuscript.

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Correspondence to Jeyaprakash Rajendhran.

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Pranav, P.S., Mahalakshmi, B., Sivakumar, R. et al. Whole-Genome Sequence Analysis of Paenibacillus alvei JR949 Revealed Biosynthetic Gene Clusters Coding for Novel Antimicrobials. Curr Microbiol 78, 1168–1176 (2021). https://doi.org/10.1007/s00284-021-02393-0

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