Immunology Program, Sloan Kettering Institute, Memorial Sloan Kettering Cancer Center, New York, New York, USA.
Louis V. Gerstner Jr. Graduate School of Biomedical Sciences, Memorial Sloan Kettering Cancer Center, New York, New York, USA.
Infect Immun. 2020 Mar 23;88(4). doi: 10.1128/IAI.00012-20.
The complex bacterial populations that constitute the gut microbiota can harbor antibiotic resistance genes (ARGs), including those encoding β-lactamase enzymes (BLA), which degrade commonly prescribed antibiotics such as ampicillin. The prevalence of such genes in commensal bacteria has been increased in recent years by the wide use of antibiotics in human populations and in livestock. While transfer of ARGs between bacterial species has well-established dramatic public health implications, these genes can also function in within bacterial consortia, where antibiotic-resistant bacteria can provide antibiotic-sensitive neighbors with leaky protection from drugs, as shown both and , in models of lung and subcutaneous coinfection. However, whether the expression of ARGs by harmless commensal bacterial species can destroy antibiotics in the intestinal lumen and shield antibiotic-sensitive pathogens is unknown. To address this question, we colonized germfree or wild-type mice with a model intestinal commensal strain of that produces either functional or defective BLA. Mice were subsequently infected with or , followed by treatment with oral ampicillin. The production of functional BLA by commensal markedly reduced clearance of these pathogens and enhanced systemic dissemination during ampicillin treatment. Pathogen resistance was independent of ARG acquisition via horizontal gene transfer but instead relied on antibiotic degradation in the intestinal lumen by BLA. We conclude that commensal bacteria that have acquired ARGs can mediate shielding of pathogens from the bactericidal effects of antibiotics.
构成肠道微生物群的复杂细菌种群可能携带有抗生素耐药基因（ARGs），包括编码β-内酰胺酶（BLA）的基因，这些酶可以降解常用的抗生素，如氨苄西林。近年来，由于抗生素在人类和牲畜中的广泛使用，共生菌中此类基因的流行率有所增加。虽然 ARGs 在细菌物种之间的转移对公共卫生有明显的影响，但这些基因也可以在细菌群落中发挥作用，在那里，抗生素耐药细菌可以为抗生素敏感的邻居提供从药物中漏出的保护，正如在肺和皮下共感染模型中 和 所显示的那样。然而，无害共生细菌物种表达 ARGs 是否会破坏肠道腔中的抗生素并保护抗生素敏感的病原体尚不清楚。为了解决这个问题，我们用产生功能性或缺陷性 BLA 的模型肠道共生菌株定植无菌或野生型小鼠。随后，用 或 感染小鼠，然后用口服氨苄西林治疗。共生 产生功能性 BLA 可显著降低这些病原体的清除率，并在氨苄西林治疗期间增强全身传播。病原体耐药性与通过水平基因转移获得 ARG 无关，而是依赖于 BLA 在肠道腔中对抗生素的降解。我们得出结论，获得 ARG 的共生细菌可以介导病原体免受抗生素杀菌作用的影响。
