Whole-genome analysis of a novel Pandoraea sputorum lineage causing high-mortality bloodstream infections

Background. Pandoraea sputorum is an emerging multidrug-resistant pathogen primarily associated with cystic fibrosis. Bloodstream infections (BSIs) are rare but linked to high mortality. The genomic characteristics and evolutionary history of P. sputorum lineages causing BSIs remain poorly understood.Methods. We performed whole-genome sequencing on 18 P. sputorum isolates recovered from patients with BSIs in China between June 2022 and March 2024. Phylogenetic relationships were determined by core-genome SNP analysis, and the pan-genome was characterized using Roary. Antimicrobial resistance and virulence genes were identified using the CARD and VFDB databases. Evolutionary timescales were estimated using Bayesian molecular clock analysis.Results. The case fatality rate among patients was 27.8% (5 out of 18). Common clinical manifestations included fever (83.3%, 15 out of 18), productive cough (77.8%, 14 out of 18) and dyspnoea (61.1%, 11 out of 18). All isolates formed a distinct monophyletic lineage, genetically distant (>2,000 SNPs) from known P. sputorum strains but with minimal intra-lineage diversity (15-98 SNPs), indicating recent clonal expansion. The pan-genome was highly conserved, with core genes comprising 94.6% of the gene repertoire. All strains harboured core genome-encoded ceoB (efflux pump) and OXA-155 (β-lactamase) genes, conferring resistance to multiple antimicrobials but remaining susceptible to imipenem. Bayesian analysis estimated the origin of this lineage in 2004 (95% highest posterior density: 2003.2-2005.8), with major diversification occurring between 2007 and 2018.Conclusion. We identified a novel, recently emerged and highly clonal lineage of P. sputorum associated with high-mortality BSIs. Its stable reservoir of core genome-encoded resistance mechanisms poses a significant therapeutic challenge. This lineage represents an emerging multidrug-resistant threat to public health, necessitating enhanced surveillance and infection control measures.