The 2-methylcitrate cycle and the glyoxylate shunt in Pseudomonas aeruginosa are linked through enzymatic redundancy.

ABSTRACT: The 2-methylcitrate cycle and the glyoxylate cycle are central metabolic pathways in Pseudomonas aeruginosa, enabling the organism to utilize organic acids such as propionate and acetate during infection. Here, we show that these cycles are linked through enzymatic redundancy, with isocitrate lyase (AceA) exhibiting secondary 2-methylisocitrate lyase activity. Furthermore, we use a combination of structural analyses, enzyme kinetics, metabolomics, and targeted mutation of PrpB_Pa to demonstrate that whereas loss of PrpB function impairs growth on propionate, the promiscuous 2-methylisocitrate lyase activity of AceA compensates for this by mitigating the accumulation of toxic 2-methylcitrate cycle intermediates. Our findings suggest that simultaneous inhibition of PrpB and AceA co

SUBMITTER: Wijaya AJ 

PROVIDER: S-EPMC11982470 | biostudies-literature | 2025 Apr

REPOSITORIES: biostudies-literature