In vivo fitness of sul gene-dependent sulfonamide-resistant Escherichia coli in the mammalian gut.

IF 5 2区 生物学 Q1 MICROBIOLOGY
mSystems Pub Date : 2024-09-17 Epub Date: 2024-08-14 DOI:10.1128/msystems.00836-24
Han Jiang, Yuzhi Dong, Xue Jiao, Biao Tang, Tao Feng, Ping Li, Jiehong Fang
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引用次数: 0

Abstract

The widespread sulfonamide resistance genes sul1, sul2, and sul3 in food and gut bacteria have attracted considerable attention. In this study, we assessed the in vivo fitness of sul gene-dependent sulfonamide-resistant Escherichia coli, using a murine model. High fitness costs were incurred for sul1 and sul3 gene-dependent E. coli strains in vivo. A fitness advantage was found in three of the eight mice after intragastric administration of sul2 gene-dependent E. coli strains. We isolated three compensatory mutant strains (CMSs) independently from three mice that outcompeted the parent strain P2 in vivo. Whole-genome sequencing revealed seven identical single nucleotide polymorphism (SNP) mutations in the three CMSs compared with strain P2, an additional SNP mutation in strain S2-2, and two additional SNP mutations in strain S2-3. Furthermore, tandem mass tag-based quantitative proteomic analysis revealed abundant differentially expressed proteins (DEPs) in the CMSs compared with P2. Of these, seven key fitness-related DEPs distributed in two-component systems, galactose and tryptophan metabolism pathways, were verified using parallel reaction monitoring analysis. The DEPs in the CMSs influenced bacterial motility, environmental stress tolerance, colonization ability, carbohydrate utilization, cell morphology maintenance, and chemotaxis to restore fitness costs and adapt to the mammalian gut environment.IMPORTANCESulfonamides are traditional synthetic antimicrobial agents used in clinical and veterinary medical settings. Their long-term excessive overuse has resulted in widespread microbial resistance, limiting their application for medical interventions. Resistance to sulfonamides is primarily conferred by the alternative genes sul1, sul2, and sul3 encoding dihydropteroate synthase in bacteria. Studying the potential fitness cost of these sul genes is crucial for understanding the evolution and transmission of sulfonamide-resistant bacteria. In vitro studies have been conducted on the fitness cost of sul genes in bacteria. In this study, we provide critical insights into bacterial adaptation and transmission using an in vivo approach.

哺乳动物肠道中依赖磺胺基因的耐磺胺大肠杆菌的体内适应性。
食物和肠道细菌中广泛存在的磺胺抗性基因 sul1、sul2 和 sul3 引起了广泛关注。在这项研究中,我们利用小鼠模型评估了依赖 sul 基因的耐磺胺大肠杆菌的体内适应性。依赖 sul1 和 sul3 基因的大肠杆菌菌株在体内的适应性成本很高。在八只小鼠中,有三只在胃内注射依赖 sul2 基因的大肠杆菌菌株后发现了体能优势。我们从三只小鼠体内独立分离出了三个代偿突变株(CMS),它们在体内的竞争能力超过了亲本菌株P2。全基因组测序发现,与 P2 菌株相比,三个 CMS 菌株中有七个相同的单核苷酸多态性(SNP)突变,S2-2 菌株中有一个额外的 SNP 突变,S2-3 菌株中有两个额外的 SNP 突变。此外,基于串联质量标签的定量蛋白质组分析显示,与 P2 相比,CMSs 中存在大量差异表达蛋白质(DEPs)。通过平行反应监测分析,验证了其中分布在双组分系统(半乳糖和色氨酸代谢途径)中的 7 个与健康相关的关键 DEPs。CMS中的DEPs影响了细菌的运动能力、环境应激耐受性、定植能力、碳水化合物利用、细胞形态维持和趋化性,以恢复适应性成本并适应哺乳动物肠道环境。磺胺类药物长期过度使用导致微生物产生广泛的抗药性,限制了其在医疗干预中的应用。细菌对磺胺类药物的抗药性主要是由编码二氢蝶酸合成酶的替代基因 sul1、sul2 和 sul3 产生的。研究这些 sul 基因的潜在适应成本对于了解耐磺胺细菌的进化和传播至关重要。目前已对细菌中硫氨酰胺基因的适应性代价进行了体外研究。在本研究中,我们利用体内方法对细菌的适应性和传播提供了重要的见解。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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来源期刊
mSystems
mSystems Biochemistry, Genetics and Molecular Biology-Biochemistry
CiteScore
10.50
自引率
3.10%
发文量
308
审稿时长
13 weeks
期刊介绍: mSystems™ will publish preeminent work that stems from applying technologies for high-throughput analyses to achieve insights into the metabolic and regulatory systems at the scale of both the single cell and microbial communities. The scope of mSystems™ encompasses all important biological and biochemical findings drawn from analyses of large data sets, as well as new computational approaches for deriving these insights. mSystems™ will welcome submissions from researchers who focus on the microbiome, genomics, metagenomics, transcriptomics, metabolomics, proteomics, glycomics, bioinformatics, and computational microbiology. mSystems™ will provide streamlined decisions, while carrying on ASM''s tradition of rigorous peer review.
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