摘要
      抗微生物耐药性已成为对人类健康的全球性威胁。自然转化是水平基因转移的重要途径，有助于抗生素抗性基因（ARGs）在细菌中的传播。尽管人们怀疑人工甜味剂可以发挥抗菌作用，但目前尚不清楚人工甜味剂是否也会通过转化影响ARGs的水平转移。在这里，我们证明了四种常用的人工甜味剂（糖精、三氯蔗糖、阿斯巴甜和安赛蜜钾）通过baylyi不动杆菌ADP1（一种研究能力和转化的模式生物）的自然转化促进ARGs的转移。在革兰氏阳性人类病原体枯草芽孢杆菌和小鼠粪便微生物组中也发现了这种现象。我们发现，接触这些甜味剂会增加细胞包膜的通透性，并导致编码DNA摄取和易位（Com）机制的基因上调。此外，我们发现人工甜味剂诱导转化体中质粒持久性的增加。我们提出了一个数学模型，用于预测暴露于这些甜味剂对转化动力学的长期影响。总的来说，我们的发现为人工甜味剂促进的自然转化提供了见解，并强调了评估这些环境污染物抗生素样副作用的必要性。
Abstract
Antimicrobial resistance has emerged as a global threat to human health. Natural transformation is an important pathway for horizontal gene transfer, which facilitates the dissemination of antibiotic resistance genes (ARGs) among bacteria. Although it is suspected that artificial sweeteners could exert antimicrobial effects, little is known whether artificial sweeteners would also affect horizontal transfer of ARGs via transformation. Here we demonstrate that four commonly used artificial sweeteners (saccharin, sucralose, aspartame, and acesulfame potassium) promote transfer of ARGs via natural transformation in Acinetobacter baylyi ADP1, a model organism for studying competence and transformation. Such phenomenon was also found in a Gram-positive human pathogen Bacillus subtilis and mice faecal microbiome. We reveal that exposure to these sweeteners increases cell envelope permeability and results in an upregulation of genes encoding DNA uptake and translocation (Com) machinery. In addition, we find that artificial sweeteners induce an increase in plasmid persistence in transformants. We propose a mathematical model established to predict the long-term effects on transformation dynamics under exposure to these sweeteners. Collectively, our findings offer insights into natural transformation promoted by artificial sweeteners and highlight the need to evaluate these environmental contaminants for their antibiotic-like side effects.

https://www.nature.com/articles/s41396-021-01095-6