Skip to main content
Log in

A Novel Depsipeptide Produced by Paenibacillus alvei 32 Isolated from a Cystic fibrosis Patient

  • Published:
Probiotics and Antimicrobial Proteins Aims and scope Submit manuscript

Abstract

The important viscosity of the respiratory tract mucus of Cystic fibrosis (CF) patients impairs the mucociliary transport system and allows the growth of numerous micro-organisms. Among them, Pseudomonas aeruginosa and Staphylococcus aureus are known to be responsible for pulmonary infections. We imagined that CF microflora could also harbour micro-organisms naturally equipped to compete with these pathogens. A method was developed to recover these antibiotic-producing strains within 20 CF sputum. Using this approach, we have isolated an unusual Gram-positive bacterium identified as Paenibacillus alvei by Api galleries and 16S rRNA gene sequence analysis. This strain has inhibited the growth of P. aeruginosa, S. aureus and Klebsiella pneumoniae, in co-cultures. A liquid mineral medium named MODT50 was designed and optimised for the production and the recovery of the antimicrobial compounds. The supernatant has inhibited the growth of all Gram-positive strains tested, even Methicillin-resistant S. aureus. One antimicrobial compound with a peptide structure (mainly active against S. aureus, Micrococcus luteus, and Pseudomonas stutzeri) has been purified and characterised by liquid chromatography-mass spectrometry. The new active molecule (m/z 786.6) named depsipeptide l possesses a 15-guanidino-3-hydroxypentadecanoic acid side chain (m/z 298) linked on a cyclic part of four amino acids residues (Ser, two Leu/Ile, Arg). This work reports for the first time the production of such a molecule by a P. alvei strain in a mineral medium. The CF lung microflora might represent a valuable source for the discovery of new antimicrobial-producing strains.

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

Access this article

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

Instant access to the full article PDF.

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5

Similar content being viewed by others

References

  1. Altschul SF, Madden TL, Schaffer AA, Zhang J, Zhang Z, Miller W, Lipman DJ (1997) Gapped BLAST and PSI-BLAST: a new generation of protein database search programs. Nucleic Acids Res 25:3389–3402

    Article  CAS  Google Scholar 

  2. Anandaraj B, Vellaichamy A, Kachman M, Selvamanikandan A, Pegu S, Murugan V (2009) Co-production of two new peptide antibiotics by a bacterial isolate Paenibacillus alvei NP75. Biochem Biophys Res Commun 379:179–185

    Article  CAS  Google Scholar 

  3. Beatty PH, Jensen SE (2002) Paenibacillus polymyxa produces fusaricidin-type antifungal antibiotics active against Leptosphaeria maculans, the causative agent of blackleg disease of canola. Can J Microbiol 48:159–169

    Article  CAS  Google Scholar 

  4. Bittar F, Rolain JM (2010) Detection and accurate identification of new or emerging bacteria in Cystic fibrosis patients. Clin Microbiol Infect 16:809–820

    Article  CAS  Google Scholar 

  5. Butler WR, Sheils CA, Brown-Elliott BA, Charles N, Colin AA, Gant MJ, Goodill J, Toney SR, Wallace RJ Jr, Yakrus MA (2007) First isolations of Segniliparus rugosus from patients with Cystic fibrosis. J Clin Microbiol 45:3449–3452

    Article  CAS  Google Scholar 

  6. Chevrot R, Carlotti A, Sopena V, Marchand P, Rosenfeld E (2008) Megamonas rupellensis sp. nov., an anaerobe isolated from the caecum of a duck. Int J Syst Evol Microbiol 58:2921–2924

    Article  CAS  Google Scholar 

  7. Coenye T, Goris J, Spilker T, Vandamme P, LiPuma JJ (2002) Characterization of unusual bacteria isolated from respiratory secretions of Cystic fibrosis patients and description of Inquilinus limosus gen. nov., sp. nov. J Clin Microbiol 40:2062–2069

    Article  Google Scholar 

  8. Coudron PE, Payne JM, Markowitz SM (1991) Pneumonia and empyema infection associated with a Bacillus species that resembles B. alvei. J Clin Microbiol 29:1777–1779

    CAS  Google Scholar 

  9. Deng Y, Lu Z, Bi H, Lu F, Zhang C, Bie X (2011) Isolation and characterization of peptide antibiotics LI-F04 and polymyxin B6 produced by Paenibacillus polymyxa strain JSa-9. Peptides 32:1917–1923

    Article  CAS  Google Scholar 

  10. Deng Y, Lu Z, Lu F, Zhang C, Wang Y, Zhao H, Bie X (2011) Identification of LI-F type antibiotics and di-n-butyl phthalate produced by Paenibacillus polymyxa. J Microbiol Methods 85:175–182

    Article  CAS  Google Scholar 

  11. Didelot S, Bordenave-Juchereau S, Rosenfeld E, Piot JM, Sannier F (2006) Peptides released from acid goat whey by a yeast--Lactobacillus association isolated from cheese microflora. J Dairy Res 73:163–170

    Article  CAS  Google Scholar 

  12. Ding R, Wu XC, Qian CD, Teng Y, Li O, Zhan ZJ, Zhao YH (2011) Isolation and identification of lipopeptide antibiotics from Paenibacillus elgii B69 with inhibitory activity against methicillin-resistant Staphylococcus aureus. J Microbiol 49:942–949

    Article  CAS  Google Scholar 

  13. Donadio S, Monciardini D, Sosio M (2007) Polypeptide synthases and nonribosomal peptide synthetases: the emerging view from bacterial genomics. Nat Prod Rep 24:1073–1109

    Article  CAS  Google Scholar 

  14. Felnagle EA, Jackson EE, Chan YA, Podevels AM, Berti AD, McMahon MD, Thomas MG (2007) Nonribosomal peptide synthetases involved in the production of medically relevant natural products. Mol Pharm 5:191–211

    Article  Google Scholar 

  15. Geoffroy C, Mengaud J, Alouf JE, Cossart P (1990) Alveolysin, the thiol-activated toxin of Bacillus alvei, is homologous to listeriolysin O, perfringolysin O, pneumolysin, and streptolysin O and contains a single cysteine. J Bacteriol 12:7301–7305

    Google Scholar 

  16. Gibson RL, Burns JL, Ramsey BW (2003) Pathophysiology and management of pulmonary infections in Cystic fibrosis. Am J Respir Crit Care Med 168:918–951

    Article  Google Scholar 

  17. Harrison F (2007) Microbial ecology of the Cystic fibrosis lung. Microbiology 153:917–923

    Article  CAS  Google Scholar 

  18. Hermsen ED, Sullivan CJ, Rotschafer JC (2003) Polymyxins: pharmacology, pharmacokinetics, pharmacodynamics, and clinical application. Infect Dis Clin North Am 17:545–562

    Article  Google Scholar 

  19. Jewes LA, Spencer RC (1990) The incidence of anaerobes in the sputum of patients with Cystic fibrosis. J Med Microbiol 31:271–274

    Article  CAS  Google Scholar 

  20. Kajimura Y, Kaneda M (1996) Fusaricidin A, a new depsipeptide antibiotic produced by Bacillus polymyxa KT-8. Taxonomy, fermentation, isolation, structure elucidation and biological activity. J Antibiot 49:129–135

    Article  CAS  Google Scholar 

  21. Kajimura Y, Kaneda M (1997) Fusaricidins B, C and D, new depsipeptide antibiotics produced by Bacillus polymyxa KT-8: isolation, structure elucidation and biological activity. J Antibiot 50:220–228

    Article  CAS  Google Scholar 

  22. Kleinkauf H, von Dohren H (1990) Nonribosomal biosynthesis of peptide antibiotics. Eur J Biochem 192:1–15

    Article  CAS  Google Scholar 

  23. Kuroda J, Fukai T, Konishi M, Uno J, Kurusu K, Nomura T (2000) LI-F Antibiotics, a family of antifungal cyclic depsipeptides produced by Bacillus polymyxa L-1129. Heterocycles 53:1533–1549

    Article  CAS  Google Scholar 

  24. Lau GW, Hassett DJ, Britigan BE (2005) Modulation of lung epithelial functions by Pseudomonas aeruginosa. Trends Microbiol 13:389–397

    Article  CAS  Google Scholar 

  25. Leão RS, Pereira RH, Ferreira AG, Lima AN, Albano RM, Marques EA (2010) First report of Paenibacillus cineris from a patient with Cystic fibrosis. Diagn Microbiol Infect Dis 66:101–103

    Article  Google Scholar 

  26. Li J, Beatty PK, Shah S, Jensen SE (2007) Use of PCR-targeted mutagenesis to disrupt production of fusaricidin-type antifungal antibiotics in Paenibacillus polymyxa. Appl Environ Microbiol 76:3480–3489

    Article  Google Scholar 

  27. Michel-Briand Y, Baysse C (2002) The pyocins of Pseudomonas aeruginosa. Biochimie 84:499–510

    Article  CAS  Google Scholar 

  28. Pereira MF, Chevrot R, Rosenfeld E, Thiery V, Besson T (2007) Synthesis and evaluation of the antimicrobial activity of novel quinazolinones. J Enzyme Inhib Med Chem 22:577–583

    Article  CAS  Google Scholar 

  29. Reboli AC, Bryan CS, Farrar WE (1989) Bacteremia and infection of a hip prosthesis caused by Bacillus alvei. J Clin Microbiol 27:1395–1396

    CAS  Google Scholar 

  30. Reynaldi FJ, De Giusti MR, Alippi AM (2004) Inhibition of the growth of Ascosphaera apis by Bacillus and Paenibacillus strains isolated from honey. Rev Argent Microbiol 36:52–55

    CAS  Google Scholar 

  31. Rogers GB, Carroll MP, Serisier DJ, Hockey PM, Jones G, Kehagia V, Connett GJ, Bruce KD (2006) Use of 16S rRNA gene profiling by terminal restriction fragment length polymorphism analysis to compare bacterial communities in sputum and mouthwash samples from patients with Cystic fibrosis. J Clin Microbiol 44:2601–2604

    Article  CAS  Google Scholar 

  32. Rosenfeld E, Duport C, Zigha A, Schmitt P (2005) Characterization of aerobic and anaerobic vegetative growth of the food-borne pathogen Bacillus cereus F4430/73 strain. Can J Microbiol 51:149–158

    Article  CAS  Google Scholar 

  33. Sibley CD, Parkins MD, Rabin HR, Duan K, Norgaard JC, Surette MG (2008) A polymicrobial perspective of pulmonary infections exposes an enigmatic pathogen in Cystic fibrosis patients. PNAS 105:15070–15075

    Article  CAS  Google Scholar 

Download references

Acknowledgments

This study was supported by “l’Association Vaincre la Mucoviscidose”. The authors are indebted to the patients with CF from the CRCM of Nantes (France). We are grateful to Monique Bordes (CCA, La Rochelle, France) for her help with electron microscopy. We thank the Pr. Michael Givskov (Technical University of Denmark) for providing the PA01 lasB-gfp(ASV) strain. We thank Mr. Thomas Marsh for English corrections.

Author information

Authors and Affiliations

Authors

Corresponding authors

Correspondence to Romain Chevrot or Sandrine Didelot.

Additional information

Romain Chevrot and Sandrine Didelot contributed equally to this work.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Chevrot, R., Didelot, S., Van den Bossche, L. et al. A Novel Depsipeptide Produced by Paenibacillus alvei 32 Isolated from a Cystic fibrosis Patient. Probiotics & Antimicro. Prot. 5, 18–25 (2013). https://doi.org/10.1007/s12602-012-9121-z

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s12602-012-9121-z

Keywords

Navigation