Two NAD‐independent l‐lactate dehydrogenases drive l‐lactate utilization in Pseudomonas aeruginosa PAO1

Abstract

Pseudomonas aeruginosa often establishes a chronic infection in the airways of patients with cystic fibrosis (CF). l-Lactate is the most abundant carbon source in the CF sputum, and l-lactate utilization may be important for P. aeruginosa to survive in the lungs of CF patients. In this study, the key enzymes involved in l-lactate utilization by P. aeruginosa PAO1 were characterized using the synthetic CF sputum medium (SCFM). A highly conserved membrane-bound NAD-independent l-lactate dehydrogenase (l-iLDH) encoded by lldD (PA4771) and a novel flavin-containing membrane-bound l-iLDH encoded by lldA (PA2382) were both found to contribute to l-lactate utilization by P. aeruginosa PAO1. In addition, an lldD and lldA double mutant was incapable of growing in a medium containing l-lactate as the sole carbon source. This study clarifies the mechanism and importance of l-lactate catabolism, and demonstrates the first Pseudomonas spp. expressing two l-lactate-oxidizing enzymes.

Current Knowledge and Future Directions in Developing Strategies to Combat Pseudomonas aeruginosa Infection

“…There is an extensive redundancy at this metabolic node as Pa is known to produce four enzymes annotated as lactate dehydrogenases. LdhA, which reduces pyruvate to d-lactate during anaerobic survival, LldE and LldD, which oxidize d-lactate and l-lactate, respectively, during aerobic growth and the newly annotated LldA, which performs redundant l-lactate oxidation during growth in aerobic cultures [14,64]. As expected, lldA was highly expressed in the CF samples.…”

Platelet enhancement of bacterial growth during room temperature storage: mitigation through refrigeration

“…However, measured lactate levels in PLTs challenged with E. coli at RT increased through Day 2 after collection before rapidly dropping, with significant reductions in plasma lactate detected on Days 4 and 5 after collection relative to uninfected controls (p < 0.05). Curiously, despite reported lactic acid/lactate utilization mechanisms, lactate levels were significantly increased in PLTs challenged with P. aeruginosa beginning on Day 3 after collection and continuing through Day 5 relative to uninfected controls at RT (p < 0.05). Furthermore, while most RT‐stored PLT samples exhibited a maximum lactate level of around 20 mM, lactate levels in PLTs challenged with P. aeruginosa consistently exceeded 30 mM by Day 5 after collection.…”

Modeling Cystic Fibrosis Chronic Infection Using Engineered Mucus-like Hydrogels

“…A potential cause of increased P. aeruginosa growth in the healthy model could be due to the influence of epithelial cell metabolites 52,53 . While host-microbe metabolic interactions in CF airway infections have yet to be fully understood due to the complex and polymicrobial nature of these infections, there is evidence that the effectiveness of antibiotics can be modulated by host metabolites 54 such as lactate 55 .…”