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Background <p>Multidrug-resistant and biofilm-forming pathogens have become a global health challenge, contributing to persistent and hard-to-treat infections. The objective of this study was to characterize an active metabolite produced by a novel halo-thermophilic <i>Streptomyces</i> sp. CBN-1 that exhibits potent antibacterial and antibiofilm activities using a combined in-silico and experimental approach.</p> Methods &amp; results <p>In this study, a halo-thermophilic <i>Streptomyces</i> sp. CBN-1 strain was selected for its ability to grow in 10% NaCl at 40&#xa0;°C. This strain was identified using phenotypic characterizations and 16S rRNA gene sequence analysis as <i>Streptomyces rochei</i> NRRL B-2410 with 99.15% similarity. An active metabolite, CBNa-1, was extracted using <i>n-</i>butanol solvent from ISP2 broth medium and purified by HPLC. Structural characterization using electrospray ionization mass spectrometry and NMR spectroscopy identified CBNa-1 as an aromatic heterocyclic compound regulated by non-ribosomal peptide synthetase (NRPS) and type II polyketide synthase (PKS) genes. It exhibited potent activity with minimum inhibitory concentrations (MIC) ranging from 4 to 5&#xa0;µg/mL and minimum biofilm inhibitory concentrations (MBIC<sub>50%</sub>) at ½ MIC. Additionally, in-silico docking analyses showed that CBNa-1 had stronger binding affinities from − 8.7 to −8.1&#xa0;kcal/mol with isoleucyl-tRNA synthetase, glucosamine-6-phosphate synthase, penicillin-binding protein 1a, type II DNA topoisomerases, and quorum sensing compared to antibiotics (−5.7 to −7.9&#xa0;kcal/mol). Furthermore, molecular dynamic (MD) simulation showed the stability of the protein-ligand complex under physiological conditions.</p> Conclusion <p>This study reports the first identification of CBNa-1, a metabolite from prokaryotic cells, with potent antibacterial and anti-biofilm properties to combat nosocomial infections caused by MDR pathogens, including bacteria resistant to third-generation cephalosporins.</p>

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In-vitro and in-silico antibacterial and antibiofilm activities of an aromatic heterocyclic metabolite from a novel halo-thermophilic Streptomyces sp. strain CBN-1 against bacteria causing nosocomial infections

  • 期刊论文

  • 发表日期：

    2025年5月31日

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  • El-Hadj Driche,
  • Boubekeur Badji,
  • Frédéric Pont,
  • Abdelghani Zitouni

摘要

Background

Multidrug-resistant and biofilm-forming pathogens have become a global health challenge, contributing to persistent and hard-to-treat infections. The objective of this study was to characterize an active metabolite produced by a novel halo-thermophilic Streptomyces sp. CBN-1 that exhibits potent antibacterial and antibiofilm activities using a combined in-silico and experimental approach.

Methods & results

In this study, a halo-thermophilic Streptomyces sp. CBN-1 strain was selected for its ability to grow in 10% NaCl at 40 °C. This strain was identified using phenotypic characterizations and 16S rRNA gene sequence analysis as Streptomyces rochei NRRL B-2410 with 99.15% similarity. An active metabolite, CBNa-1, was extracted using n-butanol solvent from ISP2 broth medium and purified by HPLC. Structural characterization using electrospray ionization mass spectrometry and NMR spectroscopy identified CBNa-1 as an aromatic heterocyclic compound regulated by non-ribosomal peptide synthetase (NRPS) and type II polyketide synthase (PKS) genes. It exhibited potent activity with minimum inhibitory concentrations (MIC) ranging from 4 to 5 µg/mL and minimum biofilm inhibitory concentrations (MBIC50%) at ½ MIC. Additionally, in-silico docking analyses showed that CBNa-1 had stronger binding affinities from − 8.7 to −8.1 kcal/mol with isoleucyl-tRNA synthetase, glucosamine-6-phosphate synthase, penicillin-binding protein 1a, type II DNA topoisomerases, and quorum sensing compared to antibiotics (−5.7 to −7.9 kcal/mol). Furthermore, molecular dynamic (MD) simulation showed the stability of the protein-ligand complex under physiological conditions.

Conclusion

This study reports the first identification of CBNa-1, a metabolite from prokaryotic cells, with potent antibacterial and anti-biofilm properties to combat nosocomial infections caused by MDR pathogens, including bacteria resistant to third-generation cephalosporins.