Scholarlink

<p>The rise of antibiotic-resistant <i>Bacillus cereus</i> strains, particularly those carrying the <i>blaOXA</i> gene encoding oxacillinase-type β-lactamase, has significantly limited treatment options for foodborne illnesses. This study aimed to identify <i>blaOXA</i>-positive <i>Bacillus cereus</i> from environmental samples and evaluate AI-optimized phytochemicals as novel inhibitors of the blaOXA enzyme. Soil-derived bacterial isolates were identified via 16S rRNA gene amplification and Sanger sequencing. Antibiotic susceptibility was assessed using the disc diffusion method. The <i>blaOXA</i> gene was amplified and sequenced, followed by phylogenetic analysis. The blaOXA protein was modeled using AlphaFold3 and validated by the Ramachandran plot and ERRAT. Thirty phytochemicals were screened using molecular docking against blaOXA protein. Piperine emerged as the top candidate and was optimized using the WADDAICA AI tool. AI-modified derivatives were evaluated through docking, ADMET, toxicity, density functional theory (DFT), molecular dynamics (MD) simulations, and pharmacophore analysis. The isolated strain MBBL37 was confirmed as <i>B. cereus</i> (NCBI Accession: PVO14952.1), resistant to ampicillin and cefoxitin. The <i>blaOXA</i> gene (632&#xa0;bp; Accession: PV535213.1) showed phylogenetic similarity with <i>Enterobacter</i> and <i>E. coli</i>, suggesting potential horizontal transfer. The predicted blaOXA protein demonstrated high stereochemical reliability (87.8% residues in favored regions; ERRAT score: 100%). Piperine showed the best natural docking score (−&#xa0;6.9&#xa0;kcal/mol), while the AI-optimized compound 2 exhibited superior binding (−&#xa0;7.3&#xa0;kcal/mol) compared to standard antibiotics (e.g., cefotaxime, −&#xa0;6.5&#xa0;kcal/mol). MD simulations confirmed complex stability, and DFT analysis showed a favorable energy gap (0.20 a.u). AI-modified Piperine showed improved pharmacokinetics, reduced CYP interactions, and lower toxicity. However, these findings are based on in silico analyses and require further validation through in vitro and in vivo studies to confirm biological activity, safety, and therapeutic potential.</p>

错误：搜索内容不能为空，请输入英文关键词
错误：关键词超出字数限制，请精简
高级检索

Molecular identification of the blaOXA gene in Bacillus cereus and AI-driven optimization of natural phytochemicals for foodborne illness treatment

  • 期刊论文

  • 发表日期：

    2026年1月5日

查看全文
  • Muhammad Naveed,
  • Muhammad Asim,
  • Tariq Aziz,
  • Maida Salah Ud Din,
  • Muhammad Nouman Majeed,
  • Ammena Y. Binsaleh,
  • Nawal Al-Hoshani,
  • Maher S. Alwethaynani,
  • Abeer M. Alghamdi,
  • Fakhria A. Al-Joufi

摘要

The rise of antibiotic-resistant Bacillus cereus strains, particularly those carrying the blaOXA gene encoding oxacillinase-type β-lactamase, has significantly limited treatment options for foodborne illnesses. This study aimed to identify blaOXA-positive Bacillus cereus from environmental samples and evaluate AI-optimized phytochemicals as novel inhibitors of the blaOXA enzyme. Soil-derived bacterial isolates were identified via 16S rRNA gene amplification and Sanger sequencing. Antibiotic susceptibility was assessed using the disc diffusion method. The blaOXA gene was amplified and sequenced, followed by phylogenetic analysis. The blaOXA protein was modeled using AlphaFold3 and validated by the Ramachandran plot and ERRAT. Thirty phytochemicals were screened using molecular docking against blaOXA protein. Piperine emerged as the top candidate and was optimized using the WADDAICA AI tool. AI-modified derivatives were evaluated through docking, ADMET, toxicity, density functional theory (DFT), molecular dynamics (MD) simulations, and pharmacophore analysis. The isolated strain MBBL37 was confirmed as B. cereus (NCBI Accession: PVO14952.1), resistant to ampicillin and cefoxitin. The blaOXA gene (632 bp; Accession: PV535213.1) showed phylogenetic similarity with Enterobacter and E. coli, suggesting potential horizontal transfer. The predicted blaOXA protein demonstrated high stereochemical reliability (87.8% residues in favored regions; ERRAT score: 100%). Piperine showed the best natural docking score (− 6.9 kcal/mol), while the AI-optimized compound 2 exhibited superior binding (− 7.3 kcal/mol) compared to standard antibiotics (e.g., cefotaxime, − 6.5 kcal/mol). MD simulations confirmed complex stability, and DFT analysis showed a favorable energy gap (0.20 a.u). AI-modified Piperine showed improved pharmacokinetics, reduced CYP interactions, and lower toxicity. However, these findings are based on in silico analyses and require further validation through in vitro and in vivo studies to confirm biological activity, safety, and therapeutic potential.