Abstract Background Nocardia cyriacigeorgica, an opportunistic pathogen, is increasingly implicated in human infections. This pathogen predo
Abstract Background Nocardia cyriacigeorgica, an opportunistic pathogen, is increasingly implicated in human infections. This pathogen predominantly causes pulmonary infections, leading to acute, subacute, or chronic necrotizing suppurative lesions, in severe cases, may progress to disseminated infections. Effective clinical diagnosis, prevention, and treatment strategies require a thorough understanding of its biological characteristics and pathogenic mechanisms. However, despite the rising incidence of nocardial diseases, research on the pathogenicity of N. cyriacigeorgica remains limited, primarily focusing on case reports and epidemiological studies. This study aimed to provide a comprehensive analysis of the genomic features, phylogenetic relationships, antimicrobial resistance profiles, and candidate virulence factors of N. cyriacigeorgica strains to inform future investigations into its pathogenesis. Methods Whole-genome sequencing was conducted on five N. cyriacigeorgica strains isolated from patients with pulmonary infection at our hospital. This analysis utilized a combination of second-generation Illumina HiSeq and third-generation PacBio sequencing technologies. Additionally, publicly available genomic data from 58 strains in the National Center Biotechnology Information database were integrated, resulting in a dataset of 63 genomes. These genomes were subjected to comparative genomic analyses, including phylogenetic reconstruction, pan-genome evaluation, and gene distribution assessments. Results Phylogenetic analysis identified five major clades within N. cyriacigeorgica. ANI analysis further subdivided clade B into five distinct subgroups. Pan-genome analysis revealed clade-specific orthogroups in the distribution of genes assigned to Clusters of Orthologous Groups, with clade A containing the highest number of clade-specific gene families. Comparative genomic analysis uncovered several potential pathogenic genes implicated in host cell invasion, phagosomal maturation arrest, and intracellular survival within macrophages, which were conserved across all analyzed strains. Notable differences in the distribution of enterobactin-encoding genes were observed among the clades. The mce3C gene also displayed variable distributions across clades; however, no correlation was established between its presence and strain source. Among the 63 strains, 27 were found to harbor both mce3C and mce4F genes, which were categorized into five distinct patterns. Furthermore, antibiotic resistance genes, including VanSO, VanRO, erm(O)-Irm, srmB, ermH, bcl, bla1, and cmIR, demonstrated clade-specific distribution patterns. Notably, the genes erm(O)-Irm, srmB, and ermH were associated with the isolation origin of the strains. Conclusions This study provides a comprehensive evaluation of the genomic characteristics, potential virulence factors, antimicrobial resistance genes, and phylogenetic relationships of N. cyriacigeorgica. The findings offer valuable insights into the mechanisms underlying intracellular survival, replication within macrophages, and pathogen-host interactions in N. cyriacigeorgica infections. These results establish a foundation for future research into the pathogenesis and clinical management of N. cyriacigeorgica.
