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<p>The abundant gut commensal <i>Bacteroides thetaiotaomicron</i> is repeatedly challenged by β-lactam exposure in the human intestine, yet its β-lactamase repertoire and dissemination potential remain incompletely characterized. Here, we screened 626 publicly available <i>B. thetaiotaomicron</i> genomes and identified 1059 putative β-lactamase homologs, all belonging to class A or class D families. Four highly prevalent representatives—BTA-1 and CfxA-3 (class A) and OXA-347 and OXA-1327 (class D)—were prioritized for experimental validation. Heterologous expression in <i>Escherichia coli</i> revealed heterogeneous resistance phenotypes, with ones conferring only modest MIC increases (e.g., OXA-347, ~2-fold for amoxicillin) and others producing strong resistance to penicillins (e.g., BTA-1caused a 256-fold increase in amoxicillin MIC). Purified BTA-1 and OXA-347 were active under gut-relevant conditions, with pH optima at 7 and 8 and temperature optima at 40 °C and 30 °C, respectively. Notably, OXA-347 hydrolyzed representatives of penicillins, cephalosporins, carbapenems, and monobactams, and mass spectrometry confirmed β-lactam ring opening. Beyond <i>B. thetaiotaomicron</i>, these β-lactamase alleles were detected across multiple gut commensal genera as well as taxa annotated as opportunistic pathogens. Genomic context analyses showed similar gene-cluster patterns in <i>B. thetaiotaomicron</i>, across gut commensal genera, and in opportunistic-pathogen–associated taxa. Collectively, our findings clarify the diversity, activity, and distribution of <i>B. thetaiotaomicron</i>–associated β-lactamases across the gut microbiome and clinically relevant taxa.</p>

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The gut commensal Bacteroides thetaiotaomicron harbors prevalent class A and D β-lactamases with cross-taxa dissemination potential

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2026年5月28日

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  • Tao Song,
  • Zhangqun Hou,
  • Chuan Zhang,
  • Tong Luo,
  • Peiting Wen,
  • Ling Mei,
  • Dezhi Yuan,
  • Xue Shen,
  • Hongbo Dong,
  • Kelei Zhao,
  • Yiwen Chu,
  • Xinrong Wang,
  • Fengzheng Chen,
  • Wenxia Sun,
  • Jiafu Lin,
  • Wenjun Jiang

摘要

The abundant gut commensal Bacteroides thetaiotaomicron is repeatedly challenged by β-lactam exposure in the human intestine, yet its β-lactamase repertoire and dissemination potential remain incompletely characterized. Here, we screened 626 publicly available B. thetaiotaomicron genomes and identified 1059 putative β-lactamase homologs, all belonging to class A or class D families. Four highly prevalent representatives—BTA-1 and CfxA-3 (class A) and OXA-347 and OXA-1327 (class D)—were prioritized for experimental validation. Heterologous expression in Escherichia coli revealed heterogeneous resistance phenotypes, with ones conferring only modest MIC increases (e.g., OXA-347, ~2-fold for amoxicillin) and others producing strong resistance to penicillins (e.g., BTA-1caused a 256-fold increase in amoxicillin MIC). Purified BTA-1 and OXA-347 were active under gut-relevant conditions, with pH optima at 7 and 8 and temperature optima at 40 °C and 30 °C, respectively. Notably, OXA-347 hydrolyzed representatives of penicillins, cephalosporins, carbapenems, and monobactams, and mass spectrometry confirmed β-lactam ring opening. Beyond B. thetaiotaomicron, these β-lactamase alleles were detected across multiple gut commensal genera as well as taxa annotated as opportunistic pathogens. Genomic context analyses showed similar gene-cluster patterns in B. thetaiotaomicron, across gut commensal genera, and in opportunistic-pathogen–associated taxa. Collectively, our findings clarify the diversity, activity, and distribution of B. thetaiotaomicron–associated β-lactamases across the gut microbiome and clinically relevant taxa.