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.

抗菌素耐药性已成为对人类健康的全球威胁。自然转化是水平基因转移的重要途径，它促进了抗生素抗性基因（ARGs）在细菌之间的传播。尽管人们怀疑人造甜味剂可以发挥抗菌作用，但鲜为人知的是，人造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造甜味剂（糖精、三氯蔗糖、阿斯巴甜和乙酰磺胺酸钾）通过自然转化在贝利不动杆菌 ADP1（一种用于研究能力和转化的模式生物）中促进 ARGs 的转移。在革兰氏阳性人类病原体枯草芽孢杆菌中也发现了这种现象和小鼠粪便微生物组。我们揭示暴露于这些甜味剂会增加细胞包膜通透性，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，用于预测在暴露于这些甜味剂的情况下对转化动力学的长期影响。总的来说，我们的研究结果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的抗生素类副作用的必要性。