비교유전체 연구를 통한 에어로모나스 유래 고이동성 내성체의 이속 간 전파 규명 = Comparative Genomics of the Genus Aeromonas Reveals a Highly Mobile Antibiotic Resistome and Its Intergenus Transmission

다국어 초록 (Multilingual Abstract)

The genus Aeromonas, an autochthonous bacterium in aquatic ecosystems, has been recognized as a major reservoir and transmission route of antibiotic resistance genes (ARGs), yet its contribution to global ARG dissemination remains unclear. Here, a comparative genomic analysis was conducted using 1,577 publicly available Aeromonas genomes to characterize its role in ARG transmission. A total of 130 ARGs were detected, showing a temporal increase in ARG density and a strong association with mobile genetic elements (MGEs). Among these, 104 were classified as mobile ARGs, and 63 were further designated as highly mobile ARGs in Aeromonas based on their conserved genetic contexts across Aeromonas species. These 63 ARGs accounted for the temporal ARG increase in this taxon and exhibited ambiguous taxonomic delineation. To investigate inter-genus transmission, the distribution of genetic contexts of mobile ARGs was investigated across 338,782 bacterial genomes, revealing that among the 63 highly mobile ARGs in Aeromonas, 50 were highly mobile in Pseudomonadota, predominantly within Enterobacteriaceae. Insertion sequence profiles surrounding these 50 ARGs between Aeromonas species and other Pseudomonadota species revealed similar mobile genetic element repertoires across genera. From an alternative approach, inter-genus mobile ARG repertoires in Pseudomonadota were characterized and network analysis based on their co-occurrence patterns demonstrated that Aeromonas species contribute more substantially to ARG transmission within Pseudomonadota, particularly among enterobacterial pathogens, than previously recognized. Notably, the 50 ARGs were responsible for inter-genus transmission between Aeromonas and other Enterobacteriaceae genera. This study identifies Aeromonas species as critical environmental players in the inter-genus dissemination of mobile ARGs.

목차 (Table of Contents)

• Ⅰ. INTRODUCTION 1
• 1.1 The global burden of antimicrobial resistance 1
• 1.2 Comprehensive genomic analysis within the One Health framework for ARG dissemination 1
• 1.3 The genus Aeromonas 3
• 1.4 The aims of this study 4
• Ⅱ. MATERIALS AND METHODS 5
• 2.1 Genome data collection and their phylogenomic analysis 5
• 2.2 Genome metadata collection and their categorization 6
• 2.3 Identification of ARGs and MGEs from genome sequences 6
• 2.4 Analysis of plasmid-borne and MGE-associated ARGs: mobile ARGs 7
• 2.5 Categorization of highly mobile and less mobile ARGs 8
• 2.6 Similarity analysis of IS profiles surrounding ARG 9
• 2.7 Analysis of genetic structures of Aeromonas mobile ARGs 10
• 2.8 Inter-species Mantel correlation network based on co-occurrence patterns of mobile ARG context clusters 10
• 2.9 Statistical analysis and visualization 12
• Ⅲ. RESULTS 14
• 3.1 Genomic landscape of antibiotic resistome and mobilome in the genus Aeromonas 14
• 3.2 Temporal increase of ARGs in the genus Aeromonas and its major species 21
• 3.3 Elucidation of mobile ARGs and assessment of their degree of mobility 28
• 3.4 Taxonomic distribution of AMAC sequences in the phylum Pseudomonadota 41
• 3.5 Elucidation of highly mobile ARGs circulating between Aeromonas and other genera 44
• 3.6 Taxonomic distribution of Aeromonas mobile ARGs at the species-level 51
• 3.7 Comparison of IS repertoires of mobile ARGs between Aeromonas and other species 56
• 3.8 Shared genetic structures of highly mobile ARGs between Aeromonas and other genera 64
• 3.9 Ecological role of Aeromonas in the context of ARG transmission within the Phylum Pseudomonadota 68
• Ⅳ. DISCUSSION 79
• Ⅴ. CONCLUSION 85
• Ⅵ. REFERENCES 86
• Ⅶ. 국문초록 98