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Because L-lactate is a significant product of plant and animal metabolism, it can serve as a carbon source for\n                      <jats:italic>P. aeruginosa<\/jats:italic>\n                      in the diverse settings that it inhabits. In this study, we evaluate the production and use of two redundant\n                      <jats:italic>P. aeruginosa<\/jats:italic>\n                      L-lactate dehydrogenases, termed LldD and LldA. We confirm that the protein LldR represses\n                      <jats:italic>lldD<\/jats:italic>\n                      and identify a new transcription factor, called LldS, that activates\n                      <jats:italic>lldA<\/jats:italic>\n                      ; these distinct regulators and the genomic contexts of\n                      <jats:italic>lldD<\/jats:italic>\n                      and\n                      <jats:italic>lldA<\/jats:italic>\n                      contribute to their differential expression. We demonstrate that the\n                      <jats:italic>lldD<\/jats:italic>\n                      and\n                      <jats:italic>lldA<\/jats:italic>\n                      genes are conditionally controlled in response to lactate isomers as well as to glycolate and \u0251-hydroxybutyrate, which, like lactate, are \u0251-hydroxycarboxylates. We also show that\n                      <jats:italic>lldA<\/jats:italic>\n                      is induced when iron availability is low. Our examination of\n                      <jats:italic>lldD<\/jats:italic>\n                      and\n                      <jats:italic>lldA<\/jats:italic>\n                      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\n                      <jats:italic>lldD<\/jats:italic>\n                      and\n                      <jats:italic>lldA<\/jats:italic>\n                      contribute to persistence within host cells, underscoring the potential role of L-lactate as a carbon source during\n                      <jats:italic>P. aeruginosa\u2013<\/jats:italic>\n                      eukaryote interactions. Together, these findings help us understand the metabolism of a key resource that may promote\n                      <jats:italic>P. aeruginosa<\/jats:italic>\n                      \u2019s success as a resident of contaminated environments and animal hosts.\n                    <\/jats:p>\n                    <jats:sec>\n                      <jats:title>IMPORTANCE<\/jats:title>\n                      <jats:p>\n                        <jats:italic>Pseudomonas aeruginosa<\/jats:italic>\n                        is a major cause of lung infections in people with cystic fibrosis, of hospital-acquired infections, and of wound infections. It consumes L-lactate, which is found at substantial levels in human blood and tissues. In this study, we investigated the spatial regulation of two redundant enzymes, called LldD and LldA, which enable L-lactate metabolism in\n                        <jats:italic>P. aeruginosa<\/jats:italic>\n                        biofilms. We uncovered mechanisms and identified compounds that control the preference of\n                        <jats:italic>P. aeruginosa<\/jats:italic>\n                        for LldD versus LldA. We also showed that both enzymes contribute to its ability to survive within macrophages, a behavior that is thought to augment the chronicity and recalcitrance of infections. Our findings shed light on a key metabolic strategy used by\n                        <jats:italic>P. aeruginosa<\/jats:italic>\n                        and have the potential to inform the development of therapies targeting bacterial metabolism during infection.\n                      <\/jats:p>\n                    <\/jats:sec>\n                  <\/jats:sec>","DOI":"10.1128\/mbio.00852-24","type":"journal-article","created":{"date-parts":[[2024,8,20]],"date-time":"2024-08-20T09:03:53Z","timestamp":1724144633000},"update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":14,"title":["The L-lactate dehydrogenases of\n                    <i>Pseudomonas aeruginosa<\/i>\n                    are conditionally regulated but both contribute to survival during macrophage infection"],"prefix":"10.1128","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0009-0006-9331-0009","authenticated-orcid":false,"given":"Lindsey C.","family":"Florek","sequence":"first","affiliation":[{"name":"Department of Biological Sciences, Columbia University, New York, New York, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xi","family":"Lin","sequence":"additional","affiliation":[{"name":"Department of Biological Sciences, Columbia University, New York, New York, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4787-2565","authenticated-orcid":true,"given":"Yu-Cheng","family":"Lin","sequence":"additional","affiliation":[{"name":"Department of Dentistry, National Yang Ming Chiao Tung University, Taipei, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Min-Han","family":"Lin","sequence":"additional","affiliation":[{"name":"Department of Biological Sciences, Columbia University, New York, New York, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Arijit","family":"Chakraborty","sequence":"additional","affiliation":[{"name":"Department of Surgery, Massachusetts General Hospital, and Harvard Medical School, Boston, Massachusetts, USA"},{"name":"Shriners Hospitals for Children Boston, Boston, Massachusetts, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7587-7534","authenticated-orcid":false,"given":"Alexa","family":"Price-Whelan","sequence":"additional","affiliation":[{"name":"Department of Biological Sciences, Columbia University, New York, New York, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Liang","family":"Tong","sequence":"additional","affiliation":[{"name":"Department of Biological Sciences, Columbia University, New York, New York, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5374-4332","authenticated-orcid":false,"given":"Laurence","family":"Rahme","sequence":"additional","affiliation":[{"name":"Department of Surgery, Massachusetts General Hospital, and Harvard Medical School, Boston, Massachusetts, USA"},{"name":"Shriners Hospitals for Children Boston, Boston, Massachusetts, USA"},{"name":"Department of Microbiology, Harvard Medical School, Boston, Massachusetts, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2049-1137","authenticated-orcid":true,"given":"Lars E. 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