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ORIGINAL RESEARCH article

Front. Cell. Infect. Microbiol.
Sec. Antibiotic Resistance and New Antimicrobial drugs
Volume 15 - 2025 | doi: 10.3389/fcimb.2025.1494149

BTS1-knockout Saccharomyces cerevisiae with broad-spectrum antimicrobial activity through lactic acid accumulation

Provisionally accepted
Liu Cong Liu Cong 1Yuan Zhou Yuan Zhou 1Yu Zhang Yu Zhang 1Shanshan Mao Shanshan Mao 1Chaoqun Chen Chaoqun Chen 2Liying Wang Liying Wang 1Xiao Li Xiao Li 1Zuo Zhang Zuo Zhang 1Zuobin Zhu Zuobin Zhu 1*Ying Li Ying Li 1*
  • 1 Xuzhou Medical University, Xuzhou, China
  • 2 Xuzhou Central Hospital, Xuzhou, China

The final, formatted version of the article will be published soon.

    Bacterial infections pose significant threats to human health, and prudent antibiotic use remains a key strategy for disease treatment and control. However, a global escalation of drug resistance among pathogenic bacteria presents a formidable challenge. Probiotics have emerged as a promising approach to combatingavenue for addressing pathogenic bacterial infections. In this study, we investigated the antibacterial activity of BTS1-knockout (BTS1-KO) Saccharomyces cerevisiae. Our findings demonstrate its effective inhibition of pathogen growth as evidenced by Minimum inhibitory concentration (MIC) assays, growth curves, bacteriostatic spectrum analyses and co-culture experiments. Additionally, it significantly impedes Escherichia coli and Staphylococcus aureus biofilm formation. Moreover, BTS1-KO S. cerevisiae exhibits low hemolytic activity, acid resistance, resistance to high bile salt concentrations, high autoaggregation capacity and high co-aggregation capacities with pathogenic bacteria. Moreover, infected larvae treated with BTS1-KO S. cerevisiae in Galleria mellonella-E. coli (in vivo) and G. mellonella-S. aureus (in vivo) infection models showed significantly prolonged survival times.Mechanistic investigations revealed that BTS1-KO S. cerevisiae primarilymainly produced lactic acid via metabolism, thereby lowering the environmental pH and consequently inhibiting pathogenic bacterial growth. In summary, our study underscores the probiotic potential of BTS1-KO S. cerevisiae, offering broad-spectrum antibacterial activity in vitro and in vivo with low toxicity. This highlights BTS1-KO S. cerevisiae as a promising probiotic candidate for clinical prevention and control of bacterial infection.

    Keywords: Probiotics, Saccharomyces cerevisiae, Multidrug resistant pathogens, Broadspectrum antibacterial activity, Antimicrobial metabolites

    Received: 10 Sep 2024; Accepted: 14 Jan 2025.

    Copyright: © 2025 Cong, Zhou, Zhang, Mao, Chen, Wang, Li, Zhang, Zhu and Li. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

    * Correspondence:
    Zuobin Zhu, Xuzhou Medical University, Xuzhou, China
    Ying Li, Xuzhou Medical University, Xuzhou, China

    Disclaimer: All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.