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

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 approa...

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Main Authors: Liu Cong, Yuan Zhou, Yu Zhang, Shanshan Mao, Chaoqun Chen, Liying Wang, Xiao Li, Zuo Zhang, Zuobin Zhu, Ying Li
Format: Article
Language:English
Published: Frontiers Media S.A. 2025-01-01
Series:Frontiers in Cellular and Infection Microbiology
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Online Access:https://www.frontiersin.org/articles/10.3389/fcimb.2025.1494149/full
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author Liu Cong
Yuan Zhou
Yu Zhang
Shanshan Mao
Chaoqun Chen
Liying Wang
Xiao Li
Zuo Zhang
Zuobin Zhu
Ying Li
author_facet Liu Cong
Yuan Zhou
Yu Zhang
Shanshan Mao
Chaoqun Chen
Liying Wang
Xiao Li
Zuo Zhang
Zuobin Zhu
Ying Li
author_sort Liu Cong
collection DOAJ
description 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 combating 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 haemolytic activity, acid resistance, resistance to high bile salt concentrations, high auto-aggregation 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 primarily produced lactic acid via metabolism, thereby lowering the environmental pH and 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.
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spelling doaj-art-dc5ed98598c24b83916425b576beb72f2025-01-31T06:40:09ZengFrontiers Media S.A.Frontiers in Cellular and Infection Microbiology2235-29882025-01-011510.3389/fcimb.2025.14941491494149BTS1-knockout Saccharomyces cerevisiae with broad-spectrum antimicrobial activity through lactic acid accumulationLiu Cong0Yuan Zhou1Yu Zhang2Shanshan Mao3Chaoqun Chen4Liying Wang5Xiao Li6Zuo Zhang7Zuobin Zhu8Ying Li9School of Medical Technology, Xuzhou Medical University, Xuzhou, Jiangsu, ChinaSchool of Medical Technology, Xuzhou Medical University, Xuzhou, Jiangsu, ChinaSchool of Medical Technology, Xuzhou Medical University, Xuzhou, Jiangsu, ChinaSchool of Medical Technology, Xuzhou Medical University, Xuzhou, Jiangsu, ChinaDepartment of Clinical Laboratory, Xuzhou Central Hospital, Xuzhou, Jiangsu, ChinaDepartment of Genetics, Xuzhou Medical University, Xuzhou, Jiangsu, ChinaSchool of Medical Technology, Xuzhou Medical University, Xuzhou, Jiangsu, ChinaSchool of Medical Technology, Xuzhou Medical University, Xuzhou, Jiangsu, ChinaDepartment of Genetics, Xuzhou Medical University, Xuzhou, Jiangsu, ChinaSchool of Medical Technology, Xuzhou Medical University, Xuzhou, Jiangsu, ChinaBacterial 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 combating 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 haemolytic activity, acid resistance, resistance to high bile salt concentrations, high auto-aggregation 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 primarily produced lactic acid via metabolism, thereby lowering the environmental pH and 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.https://www.frontiersin.org/articles/10.3389/fcimb.2025.1494149/fullprobioticsSaccharomyces cerevisiaemultidrug resistant pathogensbroadspectrum antibacterial activityantimicrobial metabolites
spellingShingle Liu Cong
Yuan Zhou
Yu Zhang
Shanshan Mao
Chaoqun Chen
Liying Wang
Xiao Li
Zuo Zhang
Zuobin Zhu
Ying Li
BTS1-knockout Saccharomyces cerevisiae with broad-spectrum antimicrobial activity through lactic acid accumulation
Frontiers in Cellular and Infection Microbiology
probiotics
Saccharomyces cerevisiae
multidrug resistant pathogens
broadspectrum antibacterial activity
antimicrobial metabolites
title BTS1-knockout Saccharomyces cerevisiae with broad-spectrum antimicrobial activity through lactic acid accumulation
title_full BTS1-knockout Saccharomyces cerevisiae with broad-spectrum antimicrobial activity through lactic acid accumulation
title_fullStr BTS1-knockout Saccharomyces cerevisiae with broad-spectrum antimicrobial activity through lactic acid accumulation
title_full_unstemmed BTS1-knockout Saccharomyces cerevisiae with broad-spectrum antimicrobial activity through lactic acid accumulation
title_short BTS1-knockout Saccharomyces cerevisiae with broad-spectrum antimicrobial activity through lactic acid accumulation
title_sort bts1 knockout saccharomyces cerevisiae with broad spectrum antimicrobial activity through lactic acid accumulation
topic probiotics
Saccharomyces cerevisiae
multidrug resistant pathogens
broadspectrum antibacterial activity
antimicrobial metabolites
url https://www.frontiersin.org/articles/10.3389/fcimb.2025.1494149/full
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