(689b) Mucin Driven Metabolic Reprogramming in Pseudomonas Aeruginosa Clinical Isolates

Pseudomonas aeruginosa is a leading cause of infections in immunocompromised individuals in healthcare settings. The presence of a large variety of metabolic and virulence mechanisms among clinical strains complicates the treatment of these infections. However, these differences in metabolic functions are poorly characterized. We hypothesize that the metabolic differences in P. aeruginosa are dependent on a complex combination of host and pathogen-specific factors, which can be delineated using a combination of genomic and transcriptomic analyses coupled with genome-scale metabolic modeling.

Mucins, the primary component of mucus, are known to modulate microbial phenotypes important in infectious disease. We experimentally profiled the metabolic phenotypes of a representative set of clinical P. aeruginosa isolates in a synthetic cystic fibrosis growth medium (SCFM) in the presence of mucin, specifically MUC5AC. We observed mucin-induced transcriptional changes across many central and peripheral metabolic pathways across all the clinical isolates. Five clinical isolates, along with the reference strain PA14 were selected for transcriptomic sequencing using static cultures in SCFM ± 0.5% MUC5AC. Specific metabolic functions and biological processes modulated by the presence of mucin were identified using differential gene expression analysis. Mucin-driven metabolic shifts were observed in various central and peripheral metabolic pathways, which include both shared and unique metabolic functions across the clinical isolates studied. Furthermore, the transcriptomic datasets were analyzed and incorporated into the genome-scale metabolic models of the clinical isolates, allowing for the identification of mucin-driven metabolic changes. Characterizing this rich set of clinical P. aeruginosa 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 mucin-induced metabolic modulations during infection.