Malonate is relevant to the lung environment and induces genome-wide stress responses in Pseudomonas aeruginosa

Versatility in carbon source utilization is a major contributor to niche adaptation in Pseudomonas aeruginosa. Malonate is among the abundant carbon sources in the lung airways, yet it is understudied. Recently, we characterized how malonate impacts quorum sensing regulation, antibiotic resistance, and virulence factor production in P. aeruginosa. Herein, we show that malonate as a carbon source supports more robust growth in comparison to glycerol in several cystic fibrosis isolates of P. aeruginosa. Furthermore, we show phenotypic responses to malonate were conserved among clinical strains, i.e., formation of biomineralized biofilm-like aggregates, increased tolerance to kanamycin, and increased susceptibility to norfloxacin. Moreover, we explored transcriptional adaptations of P. aeruginosa UCBPP-PA14 (PA14) in response to malonate versus glycerol as a sole carbon source using transcriptomics. Malonate utilization activated glyoxylate and methylcitrate cycles and induced several stress responses, including oxidative, anaerobic, and metal stress responses associated with increases in intracellular aluminum and strontium. We identified several genes that were required for optimal growth of P. aeruginosa in malonate. Our findings reveal important remodeling of P. aeruginosa gene expression during its growth on malonate as a sole carbon source that is accompanied by several important phenotypic changes. These findings add to the accumulating literature highlighting the role of different carbon sources in the physiology of P. aeruginosa and its niche adaptation.