{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,5,14]],"date-time":"2025-05-14T04:14:38Z","timestamp":1747196078111,"version":"3.40.5"},"reference-count":79,"publisher":"Public Library of Science (PLoS)","issue":"8","license":[{"start":{"date-parts":[[2021,8,13]],"date-time":"2021-08-13T00:00:00Z","timestamp":1628812800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["www.plosone.org"],"crossmark-restriction":false},"short-container-title":["PLoS ONE"],"abstract":"<jats:p>The zoonotic pathogen <jats:italic>Coxiella burnetii<\/jats:italic>, the causative agent of the human disease Q fever, is an ever-present danger to global public health. Investigating novel metabolic pathways necessary for <jats:italic>C<\/jats:italic>. <jats:italic>burnetii<\/jats:italic> to replicate within its unusual intracellular niche may identify new therapeutic targets. Recent studies employing stable isotope labelling established the ability of <jats:italic>C<\/jats:italic>. <jats:italic>burnetii<\/jats:italic> to synthesize lactate, despite the absence of an annotated synthetic pathway on its genome. A noncanonical lactate synthesis pathway could provide a novel anti-<jats:italic>Coxiella<\/jats:italic> target if it is essential for <jats:italic>C<\/jats:italic>. <jats:italic>burnetii<\/jats:italic> pathogenesis. In this study, two <jats:italic>C<\/jats:italic>. <jats:italic>burnetii<\/jats:italic> proteins, CBU1241 and CBU0823, were chosen for analysis based on their similarities to known lactate synthesizing enzymes. Recombinant GST-CBU1241, a putative malate dehydrogenase (MDH), did not produce measurable lactate in <jats:italic>in vitro<\/jats:italic> lactate dehydrogenase (LDH) activity assays and was confirmed to function as an MDH. Recombinant 6xHis-CBU0823, a putative NAD<jats:sup>+<\/jats:sup>-dependent malic enzyme, was shown to have both malic enzyme activity and MDH activity, however, did not produce measurable lactate in either LDH or malolactic enzyme activity assays <jats:italic>in vitro<\/jats:italic>. To examine potential lactate production by CBU0823 more directly, [<jats:sup>13<\/jats:sup>C]glucose labelling experiments compared label enrichment within metabolic pathways of a <jats:italic>cbu0823<\/jats:italic> transposon mutant and the parent strain. No difference in lactate production was observed, but the loss of CBU0823 significantly reduced <jats:sup>13<\/jats:sup>C-incorporation into glycolytic and TCA cycle intermediates. This disruption to central carbon metabolism did not have any apparent impact on intracellular replication within THP-1 cells. This research provides new information about the mechanism of lactate biosynthesis within <jats:italic>C<\/jats:italic>. <jats:italic>burnetii<\/jats:italic>, demonstrating that CBU1241 is not multifunctional, at least <jats:italic>in vitro<\/jats:italic>, and that CBU0823 also does not synthesize lactate. Although critical for normal central carbon metabolism of <jats:italic>C<\/jats:italic>. <jats:italic>burnetii<\/jats:italic>, loss of CBU0823 did not significantly impair replication of the bacterium inside cells.<\/jats:p>","DOI":"10.1371\/journal.pone.0255925","type":"journal-article","created":{"date-parts":[[2021,8,13]],"date-time":"2021-08-13T17:39:36Z","timestamp":1628876376000},"page":"e0255925","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":2,"title":["Characterisation of putative lactate synthetic pathways of Coxiella burnetii"],"prefix":"10.1371","volume":"16","author":[{"given":"Janine","family":"Hofmann","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mebratu 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