Klebsiella pneumoniae is a notorious hospital pathogen and major contributor to the global antimicrobial resistance crisis. However, it is also a common asymptomatic coloniser of the human gut, a wide variety of animal and plant hosts, as well as the environment. The species population can be subdivided into hundreds of distinct groups of closely related individuals, known as ‘clones,’ that share access to a diverse pool of >100,000 protein coding genes. Almost all clones appear capable of causing human disease and to-date no clear niche associations have been identified, so it remains unclear how so many can co-exist in the population.
My team is leveraging the latest genome-scale metabolic modelling approaches in combination with comparative genomics analyses, to explore the metabolic diversity of K. pneumoniae and its distribution within the population. Here I will discuss our findings from comparative analysis of >7000 K. pneumoniae, for which we have generated strain-specific metabolic models and predicted >7 million individual growth phenotypes. Our data highlight considerable metabolic diversity that is driven by gene content variation and is non-randomly distributed in the population. We demonstrate that each of 50 common clones is associated with its own unique core substrate usage profile (conserved among ≥95% clone members), and that differentially core phenotypes include those implicated in colonisation and competition within the mammalian gut (e.g. the ability to use galactitol and fructoselysine as carbon sources). We propose that these clone-specific profiles facilitate their coexistence in diverse ecological niches, by limiting nutrient competition and enhancing metabolic cooperation.