Genomic Insights into a New Burkholderia cenocepacia Sequence Type Linked to Cepacia Syndrome in Cystic Fibrosis

Burkholderia cenocepacia is an important pathogen in cystic fibrosis (CF) patients, responsible for chronic lung infections and, in severe cases, cepacia syndrome (CS), characterized by necrotizing pneumonia, bacteremia, and high mortality. Epidemic lineages, such as B. cenocepacia J2315 (ET12) and ST32, are highly transmissible and frequently associated with CS. In this study, five B. cenocepacia isolates recovered from sputum and blood samples of a pediatric CF patient who developed CS were sequenced and analyzed in silico using multilocus sequence typing (MLST), phylogenomics, genomic similarity metrics, and comparative genomics to identify virulence determinants, resistance genes, and mobile genetic elements. A novel sequence type (ST2424), not associated with any known clonal complex, was identified. Phylogenomic analysis revealed high genetic relatedness among the isolates, consistent with a monoclonal infection undergoing within-host microevolution. Comparative analyses revealed distinct genetic profiles: aaiB (T6SS) was present in all isolates, whereas narG and manCcore were exclusive to bloodstream isolates. Acquired resistance determinants, including bla_OXA-1043, sul1, aac(6')-IIc, and aadA1, were detected and were absent from the reference strains B. cenocepacia J2315 and ST32. Mobile genetic elements, including insertion sequences from the IS3, IS5, and IS200/IS605 families, as well as a putatively conjugative plasmid encoding Tra/Trb subunits of the type IV secretion system, were also identified. These findings describe a novel B. cenocepacia sequence type associated with fatal CS and highlight the high genomic plasticity of this species, reinforcing the importance of genomic surveillance to detect emerging variants and improve clinical management in CF.