The L-lactate dehydrogenases of Pseudomonas aeruginosa are conditionally regulated but both contribute to survival during macrophage infection

作者：Lindsey C. Florek, Xi Lin, Yu‐Cheng Lin, Min-Han Lin, Arijit Chakraborty, Alexa Price‐Whelan, Liang Tong, Laurence G. Rahme, Lars E. P. Dietrich · 发表于：mBio · 年份：2024 · DOI：10.1128/mbio.00852-24 · 被引用次数：9 · 研究领域：Bacterial biofilms and quorum sensing、Bacterial Genetics and Biotechnology、Lipid Membrane Structure and Behavior

ABSTRACT Pseudomonas aeruginosa is an opportunistic pathogen that thrives in environments associated with human activity, including soil and water altered by agriculture or pollution. Because L-lactate is a significant product of plant and animal metabolism, it can serve as a carbon source for P. aeruginosa in the diverse settings that it inhabits. In this study, we evaluate the production and use of two redundant P. aeruginosa L-lactate dehydrogenases, termed LldD and LldA. We confirm that the protein LldR represses lldD and identify a new transcription factor, called LldS, that activates lldA ; these distinct regulators and the genomic contexts of lldD and lldA contribute to their differential expression. We demonstrate that the lldD and lldA genes are conditionally controlled in response to lactate isomers as well as to glycolate and ɑ-hydroxybutyrate, which, like lactate, are ɑ-hydroxycarboxylates. We also show that lldA is induced when iron availability is low. Our examination of lldD and lldA expression across depth in biofilms indicates a complex pattern that is consistent with the effects of glycolate production, iron availability, and cross-regulation on enzyme preference. Finally, macrophage infection assays reveal that both lldD and lldA contribute to persistence within host cells, underscoring the potential role of L-lactate as a carbon source during P. aeruginosa– eukaryote interactions. Together, these findings help us understand the metabolism of a key resource...