Key Laboratory of Specialty Agri-products Quality and Hazard Controlling Technology of Zhejiang Province, College of Life Sciences, China Jiliang University, Hangzhou, Zhejiang, China.
School of Life Science, Hangzhou Institute for Advanced Study, University of Chinese Academy of Sciences, Hangzhou, Zhejiang, China.
mSystems. 2024 Sep 17;9(9):e0083624. doi: 10.1128/msystems.00836-24. Epub 2024 Aug 14.
The widespread sulfonamide resistance genes , , and in food and gut bacteria have attracted considerable attention. In this study, we assessed the fitness of gene-dependent sulfonamide-resistant , using a murine model. High fitness costs were incurred for and gene-dependent strains . A fitness advantage was found in three of the eight mice after intragastric administration of gene-dependent strains. We isolated three compensatory mutant strains (CMSs) independently from three mice that outcompeted the parent strain P2 . 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 , , and encoding dihydropteroate synthase in bacteria. Studying the potential fitness cost of these genes is crucial for understanding the evolution and transmission of sulfonamide-resistant bacteria. studies have been conducted on the fitness cost of genes in bacteria. In this study, we provide critical insights into bacterial adaptation and transmission using an approach.
食品和肠道细菌中广泛存在的磺胺类耐药基因 、 和 引起了人们的极大关注。在本研究中，我们使用小鼠模型评估了 基因依赖性磺胺类耐药 的适应性。 基因依赖性 菌株的 和 菌株的适应性代价很高。在 8 只小鼠中有 3 只经灌胃给予 基因依赖性 菌株后，发现了适应性优势。我们从 3 只小鼠中独立分离出 3 株补偿突变株（CMS），与亲本菌株 P2 相比，这 3 株 CMS 竞争优势明显。全基因组测序显示，与 P2 相比，这 3 株 CMS 中有 7 个相同的单核苷酸多态性（SNP）突变，在 S2-2 菌株中有一个额外的 SNP 突变，在 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学分析显示，CMS 中与 P2 相比有大量差异表达蛋白（DEPs）。其中，通过平行反应监测分析验证了在 CMS 中与 P2 相比有 7 个关键的与适应性相关的差异表达蛋白（DEPs），这些 DEPs 分布在两个组分系统中，半乳糖和色氨酸代谢途径，影响细菌的运动性、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，以恢复适应性代价并适应哺乳动物肠道环境。重要性磺胺类药物是传统的合成抗菌剂，在临床和兽医医学领域中使用。它们的长期过度使用导致了微生物的广泛耐药性，限制了它们在医疗干预中的应用。磺胺类药物的耐药性主要由替代基因 、 和 编码二氢喋呤合成酶赋予细菌。研究这些 基因的潜在适应性代价对于理解磺胺类耐药菌的进化和传播至关重要。已有研究对 基因在细菌中的适应性代价进行了研究。在本研究中，我们使用 方法提供了对细菌适应性和传播的重要见解。
