A metabolic atlas of the Klebsiella pneumoniae species complex reveals lineage-specific metabolism that supports persistent co-existence of diverse lineages

The Klebsiella pneumoniae species complex inhabits a wide variety of hosts and environments. Genomics has revealed the population comprises multiple species/subspecies and hundreds of distinct co-circulating sub-lineages that are associated with distinct gene complements. These data are consistent with metabolic differentiation as a driver of population structure, but this has so far remained unsubstantiated. Here we used comparative genomics and genome-scale metabolic modelling to systematically explore metabolic diversity across the population (n=7,835 genomes). We simulated growth outcomes for carbon, nitrogen, phosphorus and sulfur sources under aerobic and anaerobic conditions (n=1,278), and confirmed that sub-lineages exhibit unique metabolic profiles. In vitro co-culture experiments demonstrated reciprocal commensalistic cross-feeding between sub-lineages, effectively extending the range of conditions supporting individual growth. We propose that these substrate specialisations promote the existence and persistence of co-circulating sub-lineages by reducing nutrient competition and facilitating commensal interactions.