Culture and genome-based analysis of four soil Clostridium isolates reveal their potential for antimicrobial production.
Antimicrobial
Biosynthesis gene clusters
Clostridium spp.
Genome mining
Non-ribosomal peptides
Ribosomally synthesized post-translationally modified peptides
Journal
BMC genomics
ISSN: 1471-2164
Titre abrégé: BMC Genomics
Pays: England
ID NLM: 100965258
Informations de publication
Date de publication:
22 Sep 2021
22 Sep 2021
Historique:
received:
11
05
2021
accepted:
13
09
2021
entrez:
22
9
2021
pubmed:
23
9
2021
medline:
24
9
2021
Statut:
epublish
Résumé
Soil bacteria are a major source of specialized metabolites including antimicrobial compounds. Yet, one of the most diverse genera of bacteria ubiquitously present in soil, Clostridium, has been largely overlooked in bioactive compound discovery. As Clostridium spp. thrive in extreme environments with their metabolic mechanisms adapted to the harsh conditions, they are likely to synthesize molecules with unknown structures, properties, and functions. Therefore, their potential to synthesize small molecules with biological activities should be of great interest in the search for novel antimicrobial compounds. The current study focused on investigating the antimicrobial potential of four soil Clostridium isolates, FS01, FS2.2 FS03, and FS04, using a genome-led approach, validated by culture-based methods. Conditioned/spent media from all four Clostridium isolates showed varying levels of antimicrobial activity against indicator microorganism; all four isolates significantly inhibited the growth of Pseudomonas aeruginosa. FS01, FS2.2, and FS04 were active against Bacillus mycoides and FS03 reduced the growth of Bacillus cereus. Phylogenetic analysis together with DNA-DNA hybridization (dDDH), average nucleotide identity (ANI), and functional genome distribution (FGD) analyses confirmed that FS01, FS2.2, and FS04 belong to the species Paraclostridium bifermentans, Clostridium cadaveris, and Clostridium senegalense respectively, while FS03 may represent a novel species of the genus Clostridium. Bioinformatics analysis using antiSMASH 5.0 predicted the presence of eight biosynthetic gene clusters (BGCs) encoding for the synthesis of ribosomally synthesized post-translationally modified peptides (RiPPs) and non-ribosomal peptides (NRPs) in four genomes. All predicted BGCs showed no similarity with any known BGCs suggesting novelty of the molecules from those predicted gene clusters. In addition, the analysis of genomes for putative virulence factors revealed the presence of four putative Clostridium toxin related genes in FS01 and FS2.2 genomes. No genes associated with the main Clostridium toxins were identified in the FS03 and FS04 genomes. The presence of BGCs encoding for uncharacterized RiPPs and NRPSs in the genomes of antagonistic Clostridium spp. isolated from farm soil indicated their potential to produce novel secondary metabolites. This study serves as a basis for the identification and characterization of potent antimicrobials from these soil Clostridium spp. and expands the current knowledge base, encouraging future research into bioactive compound production in members of the genus Clostridium.
Sections du résumé
BACKGROUND
BACKGROUND
Soil bacteria are a major source of specialized metabolites including antimicrobial compounds. Yet, one of the most diverse genera of bacteria ubiquitously present in soil, Clostridium, has been largely overlooked in bioactive compound discovery. As Clostridium spp. thrive in extreme environments with their metabolic mechanisms adapted to the harsh conditions, they are likely to synthesize molecules with unknown structures, properties, and functions. Therefore, their potential to synthesize small molecules with biological activities should be of great interest in the search for novel antimicrobial compounds. The current study focused on investigating the antimicrobial potential of four soil Clostridium isolates, FS01, FS2.2 FS03, and FS04, using a genome-led approach, validated by culture-based methods.
RESULTS
RESULTS
Conditioned/spent media from all four Clostridium isolates showed varying levels of antimicrobial activity against indicator microorganism; all four isolates significantly inhibited the growth of Pseudomonas aeruginosa. FS01, FS2.2, and FS04 were active against Bacillus mycoides and FS03 reduced the growth of Bacillus cereus. Phylogenetic analysis together with DNA-DNA hybridization (dDDH), average nucleotide identity (ANI), and functional genome distribution (FGD) analyses confirmed that FS01, FS2.2, and FS04 belong to the species Paraclostridium bifermentans, Clostridium cadaveris, and Clostridium senegalense respectively, while FS03 may represent a novel species of the genus Clostridium. Bioinformatics analysis using antiSMASH 5.0 predicted the presence of eight biosynthetic gene clusters (BGCs) encoding for the synthesis of ribosomally synthesized post-translationally modified peptides (RiPPs) and non-ribosomal peptides (NRPs) in four genomes. All predicted BGCs showed no similarity with any known BGCs suggesting novelty of the molecules from those predicted gene clusters. In addition, the analysis of genomes for putative virulence factors revealed the presence of four putative Clostridium toxin related genes in FS01 and FS2.2 genomes. No genes associated with the main Clostridium toxins were identified in the FS03 and FS04 genomes.
CONCLUSIONS
CONCLUSIONS
The presence of BGCs encoding for uncharacterized RiPPs and NRPSs in the genomes of antagonistic Clostridium spp. isolated from farm soil indicated their potential to produce novel secondary metabolites. This study serves as a basis for the identification and characterization of potent antimicrobials from these soil Clostridium spp. and expands the current knowledge base, encouraging future research into bioactive compound production in members of the genus Clostridium.
Identifiants
pubmed: 34548019
doi: 10.1186/s12864-021-08005-2
pii: 10.1186/s12864-021-08005-2
pmc: PMC8456703
doi:
Substances chimiques
Anti-Infective Agents
0
Soil
0
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
686Informations de copyright
© 2021. The Author(s).
Références
PLoS One. 2016 Jul 28;11(7):e0159851
pubmed: 27467068
J Bacteriol. 2011 Jun;193(11):2745-55
pubmed: 21478363
Drugs Context. 2018 May 29;7:212527
pubmed: 29872449
Curr Opin Chem Biol. 2013 Aug;17(4):605-12
pubmed: 23891473
Nucleic Acids Res. 2017 Jul 3;45(W1):W42-W48
pubmed: 28472505
Appl Environ Microbiol. 2018 May 31;84(12):
pubmed: 29625984
Acta Sci Pol Technol Aliment. 2017 Oct-Dec;16(4):361-370
pubmed: 29241315
Nucleic Acids Res. 2019 Jan 8;47(D1):D687-D692
pubmed: 30395255
Int J Antimicrob Agents. 2020 May;55(5):105910
pubmed: 31991218
Fungal Genet Biol. 2010 Sep;47(9):736-41
pubmed: 20554054
Mol Biol Evol. 2018 Jun 1;35(6):1547-1549
pubmed: 29722887
Acc Chem Res. 2008 Jan;41(1):4-10
pubmed: 17506516
Appl Environ Microbiol. 1999 Dec;65(12):5436-42
pubmed: 10584001
PLoS One. 2012;7(1):e29609
pubmed: 22235310
Nat Commun. 2019 May 16;10(1):2182
pubmed: 31097708
Microbiol Resour Announc. 2020 Aug 27;9(35):
pubmed: 32855254
ACS Chem Biol. 2016 Jun 17;11(6):1737-44
pubmed: 27019323
Antibiotics (Basel). 2019 Dec 06;8(4):
pubmed: 31817707
Front Microbiol. 2019 Apr 26;10:902
pubmed: 31105681
Nucleic Acids Res. 2020 Jan 8;48(D1):D454-D458
pubmed: 31612915
Mol Biol Evol. 2015 Oct;32(10):2798-800
pubmed: 26130081
BMC Bioinformatics. 2016 Apr 19;17:172
pubmed: 27094401
Appl Environ Microbiol. 2010 Apr;76(8):2487-99
pubmed: 20154113
Nucleic Acids Res. 2015 Aug 18;43(14):6761-71
pubmed: 26150420
Brief Bioinform. 2019 Jul 19;20(4):1103-1113
pubmed: 29112695
Mol Microbiol. 1990 Aug;4(8):1227-32
pubmed: 2280684
Eur J Microbiol Immunol (Bp). 2015 Mar;5(1):81-93
pubmed: 25883796
Science. 2018 Mar 23;359(6382):1411-1416
pubmed: 29567715
PLoS Pathog. 2018 Sep 12;14(9):e1007191
pubmed: 30208103
Nucleic Acids Res. 2013 Jul;41(Web Server issue):W448-53
pubmed: 23677608
J Am Chem Soc. 2003 Apr 23;125(16):4726-7
pubmed: 12696888
Bioinformatics. 2015 Oct 1;31(19):3210-2
pubmed: 26059717
Front Microbiol. 2020 Dec 04;11:608998
pubmed: 33343553
Int J Syst Evol Microbiol. 2014 Feb;64(Pt 2):316-324
pubmed: 24505069
Nat Prod Rep. 2007 Aug;24(4):735-49
pubmed: 17653357
Microbiol Resour Announc. 2020 May 7;9(19):
pubmed: 32381610
Nat Chem Biol. 2017 May;13(5):470-478
pubmed: 28244986
BMC Genomics. 2014 Nov 18;15:983
pubmed: 25407095
BMC Bioinformatics. 2013 Feb 21;14:60
pubmed: 23432962
Korean J Food Sci Anim Resour. 2015;35(2):272-6
pubmed: 26761838
J Dairy Sci. 2011 Dec;94(12):5851-6
pubmed: 22118075
BMC Bioinformatics. 2009 Jun 16;10:185
pubmed: 19531248
Cell. 2014 Jul 17;158(2):412-421
pubmed: 25036635
Nat Chem Biol. 2012 Feb 26;8(4):350-7
pubmed: 22366720
Int J Syst Evol Microbiol. 2007 Jan;57(Pt 1):81-91
pubmed: 17220447
Front Microbiol. 2012 Feb 21;3:48
pubmed: 22363326
Front Microbiol. 2017 Mar 23;8:346
pubmed: 28386247
FEMS Microbiol Lett. 1997 Dec 15;157(2):223-8
pubmed: 9435100
Appl Microbiol Biotechnol. 2012 Oct;96(1):61-7
pubmed: 22854892
Mol Pharm. 2008 Mar-Apr;5(2):191-211
pubmed: 18217713
Int J Syst Evol Microbiol. 2018 Jan;68(1):461-466
pubmed: 29292687
Nat Prod Rep. 2013 Mar;30(3):392-428
pubmed: 23263685
J Bacteriol. 1996 May;178(9):2514-20
pubmed: 8626316
Front Microbiol. 2016 Nov 11;7:1764
pubmed: 27891116
Essays Biochem. 1973;9:31-57
pubmed: 4129636
Nucleic Acids Res. 2007;35(9):3100-8
pubmed: 17452365
Nucleic Acids Res. 2019 Jul 2;47(W1):W81-W87
pubmed: 31032519
Bioinformatics. 2015 Feb 15;31(4):587-9
pubmed: 25338718