Model-driven characterization of functional diversity of clinical isolates with broadly representative phenotypes.

is a leading cause of infections in immunocompromised individuals and in healthcare settings. This study aims to understand the relationships between phenotypic diversity and the functional metabolic landscape of clinical isolates. To better understand the metabolic repertoire of in infection, we deeply profiled a representative set from a library of 971 clinical isolates with corresponding patient metadata and bacterial phenotypes. The genotypic clustering based on whole-genome sequencing of the isolates, multilocus sequence types, and the phenotypic clustering generated from a multi-parametric analysis were compared to each other to assess the genotype-phenotype correlation. Genome-scale metabolic network reconstructions were developed for each isolate through amendments to an existing PA14 network reconstruction. These network reconstructions show diverse metabolic functionalities and enhance the collective pangenome metabolic repertoire. Characterizing this rich set of clinical isolates allows for a deeper understanding of the genotypic and metabolic diversity of the pathogen in a clinical setting and lays a foundation for further investigation of the metabolic landscape of this pathogen and host-associated metabolic differences during infection.