Table 5_Comparative genomics reveals key adaptive mechanisms in pathogen host-niche specialization.xlsx

IntroductionUnderstanding the key factors that enable bacterial pathogens to adapt to new hosts is crucial, as host-microbe interactions not only influence host health but also drive bacterial genome diversification, thereby enhancing pathogen survival in various ecological niches.
MethodsWe conducted a comparative genomic analysis of 4,366 high-quality bacterial genomes isolated from various hosts and environments. Bioinformatics databases and machine learning approaches were used to identify genomic differences in functional categories, virulence factors, and antibiotic resistance genes across different ecological niches.
ResultsSignificant variability in bacterial adaptive strategies was observed. Human-associated bacteria, particularly from the phylum Pseudomonadota, exhibited higher detection rates of carbohydrate-active enzyme genes and virulence factors related to immune modulation and adhesion, indicating co-evolution with the human host. In contrast, bacteria from environmental sources, particularly those from the phyla Bacillota and Actinomycetota, showed greater enrichment in genes related to metabolism and transcriptional regulation, highlighting their high adaptability to diverse environments. Bacteria from clinical settings had higher detection rates of antibiotic resistance genes, particularly those related to fluoroquinolone resistance. Animal hosts were identified as important reservoirs of resistance genes. Key host-specific bacterial genes, such as hypB, were found to potentially play crucial roles in regulating metabolism and immune adaptation in human-associated bacteria.
DiscussionThese findings highlight niche-specific genomic features and adaptive mechanisms of bacterial pathogens. This study provides valuable insights into the genetic basis of host-pathogen interactions and offers evidence to inform pathogen transmission control, infection management, and antibiotic stewardship.

## 引言
了解细菌性致病菌适应新宿主的关键因素至关重要，因为宿主-微生物互作不仅会影响宿主健康，还会推动细菌基因组的多样化，进而提升致病菌在各类生态位中的生存能力。
## 方法
本研究对从不同宿主及环境中分离得到的4366个高质量细菌基因组开展了比较基因组学分析。我们借助生物信息学数据库与机器学习方法，识别不同生态位中细菌在功能类别、毒力因子以及抗生素抗性基因方面的基因组差异。
## 结果
研究观察到细菌的适应性策略存在显著差异。与人类相关的细菌（尤其是假单胞菌门（Pseudomonadota）细菌）的碳水化合物活性酶基因与参与免疫调控及黏附过程的毒力因子检出率更高，这表明其与人类宿主存在共演化现象。与之相对，环境来源的细菌（尤其是厚壁菌门（Bacillota）和放线菌门（Actinomycetota）细菌）在代谢相关基因与转录调控相关基因上呈现更强的富集性，凸显了其对多样环境的高度适应性。临床环境来源的细菌的抗生素抗性基因（尤其是与氟喹诺酮类耐药相关的基因）检出率更高。动物宿主被证实是抗性基因的重要储存库。研究还发现了一批宿主特异性的细菌基因（如hypB），其可能在人类相关细菌的代谢调控与免疫适应过程中发挥关键作用。
## 讨论
本研究的发现凸显了细菌性致病菌的生态位特异性基因组特征与适应性机制。本研究为理解宿主-致病菌互作的遗传基础提供了宝贵见解，同时也为致病菌传播控制、感染管理以及抗生素管理提供了理论依据。