Preferred evolutionary routes of convergence in Klebsiella pneumoniae favor siderophore acquisition over hypervirulence

Abstract

The rise of Klebsiella pneumoniae combining antimicrobial resistance and virulence genes poses a major health threat, but the evolutionary routes and phenotypic consequences of this convergence are poorly understood. Here, phylogenetics of 1,468 isolates and population analysis of 7,520 plasmids, from >50 countries through the last two decades, reveal that convergence follows preferred, constrained evolutionary paths. The dominant route involves multidrug-resistant classical K. pneumoniae acquiring conjugative IncFIB(Mar)/IncHI1B plasmids carrying an incomplete set of virulence biomarkers. Across 25 independent convergence events, the acquisition of the aerobactin siderophore locus was the only universal feature. These convergent isolates exhibit enhanced siderophore production but consistently lack the hypervirulent phenotype in vivo. In contrast, genuine hypervirulent strains that gain resistance remain rare. We conclude that enhanced siderophore production, not hypervirulence, is the primary adaptive trait driving the success of globally emerging convergent lineages, representing a distinct evolutionary state optimized for transmission rather than systemic invasion.