Yang Yaofan, Jin Xingkun, Zhao Zhe
Jiangsu Province Engineering Research Center for Marine Bio-resources Sustainable Utilization, College of Oceanography, Hohai University, Nanjing 210098, China.
Genome Biol Evol. 2025 Jul 3;17(7). doi: 10.1093/gbe/evaf128.
Antibiotic resistance mediated by β-lactamases, encoded by bla genes, is a significant global health threat, necessitating systematic studies of their diversity and evolution, particularly among pathogenic bacteria lineages. Leveraging over 6,000 quality-filtered Vibrio genomes alongside six newly sequenced marine symbiotic strains representing 128 nominal and 57 unclassified Vibrio species, our study extends taxonomic breadth and resolution for investigating β-lactamase diversity. We identified 4,431 β-lactamases across 41 species, encompassing all four Ambler classes (A-D). Among these, carbenicillin-hydrolyzing Class A β-lactamases encoded by blaCARB family were the most prevalent (60.7%) and exhibited a clade-centric distribution particularly in Harveyi clade and V. cholerae, underscoring the influence of specific ecological and evolutionary pressures. We refined carbenicillin-hydrolyzing Class A β-lactamase classification into two subfamilies: CARB-17-like (blaCARB-17-like) confined to Harveyi clade and CARB-1-like (blaCARB-1-like) found exclusively outside Harveyi clade based on phylogenetic placement, sequence similarity, and inheritance patterns, providing a clearer framework for delineating their functional and phylogenetic nuances. Notably, blaCARB-17-like genes in nonpathogenic Harveyi Subclade II showed significantly relaxed selection, accompanied by unusual mutations within key conserved motifs especially catalytic serine residues, suggesting evolutionary drift that may compromise canonical enzymatic activity. Furthermore, blaCARB-17-like genes, present as a single copy, emerged as a core gene in Harveyi clade, showing promise as a diagnostic marker for clinically significant Harveyi clade species, despite limited yet significant interspecies genetic exchanges mediated by recombination or mobile genetic elements. Our study advances the understanding of β-lactamase evolution and genomic distribution in Vibrio, with broad implications for diagnostic applications and resistance management strategies.
由bla基因编码的β-内酰胺酶介导的抗生素耐药性是对全球健康的重大威胁，因此有必要对其多样性和进化进行系统研究，特别是在病原菌谱系中。利用6000多个经过质量筛选的弧菌基因组以及代表128个命名和57个未分类弧菌物种的6个新测序的海洋共生菌株，我们的研究扩展了用于研究β-内酰胺酶多样性的分类广度和分辨率。我们在41个物种中鉴定出4431种β-内酰胺酶，涵盖所有四个安布勒分类（A - D）。其中，由blaCARB家族编码的水解羧苄青霉素的A类β-内酰胺酶最为普遍（60.7%），并且呈现出以进化枝为中心的分布，特别是在哈维氏弧菌进化枝和霍乱弧菌中，这突出了特定生态和进化压力的影响。基于系统发育位置、序列相似性和遗传模式，我们将水解羧苄青霉素的A类β-内酰胺酶分类细化为两个亚家族：局限于哈维氏弧菌进化枝的CARB - 17样（blaCARB - 17样）和仅在哈维氏弧菌进化枝之外发现的CARB - 1样（blaCARB - 1样），为描绘它们的功能和系统发育细微差别提供了更清晰的框架。值得注意的是，非致病性哈维氏弧菌亚分支II中的blaCARB - 17样基因显示出明显松弛的选择，伴随着关键保守基序内的异常突变，特别是催化丝氨酸残基，这表明进化漂移可能会损害典型的酶活性。此外，作为单拷贝存在的blaCARB - 17样基因在哈维氏弧菌进化枝中成为核心基因，尽管由重组或移动遗传元件介导的种间基因交换有限但具有重要意义，但它有望作为临床上重要的哈维氏弧菌进化枝物种的诊断标志物。我们的研究推进了对弧菌中β-内酰胺酶进化和基因组分布的理解，对诊断应用和耐药性管理策略具有广泛的意义。
