Marongiu Luigi, Brzozowska Ewa, Brykała Jan, Burkard Markus, Schmidt Herbert, Szermer-Olearnik Bożena, Venturelli Sascha
Department of Nutritional Biochemistry, University of Hohenheim, Garbenstraße 30, 70599, Stuttgart, Germany.
Department of Immunology of Infectious Diseases, Hirszfeld Institute of Immunology and Experimental Therapy, Polish Academy of Sciences, 12 R. Weigl St, Wroclaw, 53114, Poland.
Sci Rep. 2025 Jan 8;15(1):1337. doi: 10.1038/s41598-025-85186-w.
Non-nutritive sweeteners (NNS) are widely employed in foodstuffs. However, it has become increasingly evident that their consumption is associated with bacterial dysbiosis, which, in turn, is linked to several health conditions, including a higher risk of type 2 diabetes and cancer. Among the NNS, stevia, whose main component is rebaudioside A (rebA), is gaining popularity in the organic food market segment. While the effect of NNS on bacteria has been established, the impact of these sweeteners on bacterial viruses (phages) has been neglected, even though phages are crucial elements in maintaining microbial eubiosis. The present study sought to provide a proof-of-concept of the impact of NNS on phage infectivity by assessing the binding of rebA to phage proteins involved in the infection process of enteropathogenic bacteria, namely the fiber protein gp17 of Yersinia enterocolitica phage φYeO3-12 and the tubular baseplate protein gp31 of Klebsiella pneumoniae phage 32. We employed docking analysis and a panel of in vitro confirmatory tests (microscale thermophoresis, RedStarch™ depolymerization, adsorption, and lysis rates). Docking analysis indicated that NNS can bind to both fiber and baseplate proteins. Confirmatory assays demonstrated that rebA can bind gp31 and that such binding increased the protein's enzymatic activity. Moreover, the binding of rebA to gp17 resulted in a decrease in the adsorption rate of the recombinant protein to its host but increased the Yersinia bacteriolysis caused by the whole phage compared to unexposed controls. These results support the hypothesis that NNS can impair phage infectivity, albeit the resulting effect on the microbiome remains to be elucidated.
非营养性甜味剂（NNS）被广泛应用于食品中。然而，越来越明显的是，食用这些甜味剂与细菌生态失调有关，而细菌生态失调又与多种健康状况相关，包括2型糖尿病和癌症风险增加。在NNS中，主要成分是莱鲍迪苷A（rebA）的甜菊糖在有机食品市场领域越来越受欢迎。虽然NNS对细菌的影响已经明确，但这些甜味剂对细菌病毒（噬菌体）的影响却被忽视了，尽管噬菌体是维持微生物共生的关键因素。本研究旨在通过评估rebA与参与肠道致病菌感染过程的噬菌体蛋白的结合，来提供NNS对噬菌体感染性影响的概念验证，这些噬菌体蛋白分别是小肠结肠炎耶尔森菌噬菌体φYeO3-12的纤维蛋白gp17和肺炎克雷伯菌噬菌体32的管状基板蛋白gp31。我们采用了对接分析和一系列体外验证试验（微量热泳动、RedStarch™解聚、吸附和裂解率）。对接分析表明，NNS可以与纤维蛋白和基板蛋白结合。验证试验表明，rebA可以与gp31结合，并且这种结合增加了该蛋白的酶活性。此外，rebA与gp17的结合导致重组蛋白对其宿主的吸附率降低，但与未暴露的对照相比，增加了全噬菌体引起的耶尔森菌裂解。这些结果支持了NNS会损害噬菌体感染性的假设，尽管其对微生物群的最终影响仍有待阐明。
