The L-lactate dehydrogenases of Pseudomonas aeruginosa are conditionally regulated but both contribute to survival during macrophage infection
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 is available to serve as a carbon source for P. aeruginosa in the diverse settings it inhabits. Here, we evaluate P. aeruginosa's production and use of its redundant 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 - hydroxybutyrate, which, like lactate, are -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 revealed 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 that may promote P. aeruginosa's success as a resident of contaminated environments and animal hosts.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2024 |
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| Erschienen: |
2024 |
| Enthalten in: |
Zur Gesamtaufnahme - year:2024 |
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| Enthalten in: |
bioRxiv : the preprint server for biology - (2024) vom: 23. März |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Florek, Lindsey C [VerfasserIn] |
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| Anmerkungen: |
Date Revised 25.04.2024 published: Electronic Citation Status PubMed-not-MEDLINE |
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| doi: |
10.1101/2024.03.21.586142 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM370523636 |
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| 100 | 1 | |a Florek, Lindsey C |e verfasserin |4 aut | |
| 245 | 1 | 4 | |a The L-lactate dehydrogenases of Pseudomonas aeruginosa are conditionally regulated but both contribute to survival during macrophage infection |
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| 520 | |a 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 is available to serve as a carbon source for P. aeruginosa in the diverse settings it inhabits. Here, we evaluate P. aeruginosa's production and use of its redundant 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 - hydroxybutyrate, which, like lactate, are -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 revealed 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 that may promote P. aeruginosa's success as a resident of contaminated environments and animal hosts | ||
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| 700 | 1 | |a Lin, Xi |e verfasserin |4 aut | |
| 700 | 1 | |a Lin, Yu-Cheng |e verfasserin |4 aut | |
| 700 | 1 | |a Lin, Min-Han |e verfasserin |4 aut | |
| 700 | 1 | |a Chakraborty, Arijit |e verfasserin |4 aut | |
| 700 | 1 | |a Price-Whelan, Alexa |e verfasserin |4 aut | |
| 700 | 1 | |a Tong, Liang |e verfasserin |4 aut | |
| 700 | 1 | |a Rahme, Laurence |e verfasserin |4 aut | |
| 700 | 1 | |a Dietrich, Lars E P |e verfasserin |4 aut | |
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