COMPARATIVE POPULATION GENOMICS OF CLINICAL AND ENVIRONMENTAL ENTEROBACTER CLOACAE COMPLEX REVEALS SHARED LINEAGES, EXTENSIVE GENE FLOW AND NICHE-SPECIFIC ADAPTATION
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The Enterobacter cloacae complex (ECC) is an opportunistic Gram-negative bacterial group increasingly linked to multidrug resistance, healthcare-associated infections, and diverse environmental reservoirs. However, the genomic relationships between clinical and environmental ECC populations, and the mechanisms supporting their adaptation, remain incompletely understood. This study conducted a comparative genomic analysis of 100 publicly available ECC genomes, including 62 clinical and 38 environmental isolates from different geographical regions. Analyses included average nucleotide identity, multilocus sequence typing, core-genome phylogeny, comparative genome architecture, resistome, virulome, plasmidome, integron, insertion sequence, and mobile genetic element profiling. A balanced subset of 76 genomes was further used for pan-genome and source-specific functional analyses. Phylogenomic and ANI analyses showed extensive intermixing between clinical and environmental isolates, with no clear source-specific clustering. Several sequence types were shared across reservoirs, suggesting lineage overlap between clinical and environmental ECC populations. Comparative genome alignments revealed conserved chromosomal backbones together with variable accessory regions. Clinically important antimicrobial resistance genes, including blaCTX-M-15, blaNDM-1, blaNDM-5, blaKPC-2, blaKPC-4, mcr-9.1, and mcr-10, were detected, with carbapenemase genes occurring mainly in clinical isolates. Clinical genomes also carried significantly higher accessory virulence burdens than environmental genomes. Pan-genome analysis identified 18,440 gene clusters, including only 196 core genes, indicating a highly open pan-genome dominated by accessory genes. Environmental-specific genes were enriched for mobile genetic elements, while clinical-specific genes were enriched for metabolic and regulatory functions. Overall, the findings reveal strong genomic connectivity between clinical and environmental ECC populations and highlight the importance of mobile genetic elements in resistance dissemination, genome plasticity, and ecological adaptation.
