{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,20]],"date-time":"2026-08-20T16:11:22Z","timestamp":1787242282128,"version":"build-2736575974"},"reference-count":101,"publisher":"American Society for Microbiology","issue":"4","license":[{"start":{"date-parts":[[2025,4,9]],"date-time":"2025-04-09T00:00:00Z","timestamp":1744156800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2025,4,9]],"date-time":"2025-04-09T00:00:00Z","timestamp":1744156800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.asm.org\/non-commercial-tdm-license"}],"content-domain":{"domain":["journals.asm.org"],"crossmark-restriction":true},"short-container-title":["mBio"],"published-print":{"date-parts":[[2025,4,9]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title\/>\n                    <jats:p>\n                      As a zoonotic pathogen, the Lyme disease bacterium\n                      <jats:italic>Borreliella burgdorferi<\/jats:italic>\n                      has evolved unique metabolic pathways, some of which are specific and essential for its survival and thus present as ideal targets for developing new therapeutics.\n                      <jats:italic>B. burgdorferi<\/jats:italic>\n                      dispenses with the use of thiamin as a cofactor and relies on lactate dehydrogenase (BbLDH) to convert pyruvate to lactate for balancing NADH\/NAD\n                      <jats:sup>+<\/jats:sup>\n                      ratios. This report first demonstrates that BbLDH is a canonical LDH with some unique biochemical and structural features. A loss-of-function study then reveals that BbLDH is essential for\n                      <jats:italic>B. burgdorferi<\/jats:italic>\n                      survival and infectivity, highlighting its therapeutic potential. Drug screening identifies four previously unknown LDH inhibitors with minimal cytotoxicity, two of which inhibit\n                      <jats:italic>B. burgdorferi<\/jats:italic>\n                      growth. This study provides mechanistic insights into the function of BbLDH in the pathophysiology of\n                      <jats:italic>B. burgdorferi<\/jats:italic>\n                      and lays the groundwork for developing genus-specific metabolic inhibitors against\n                      <jats:italic>B. burgdorferi<\/jats:italic>\n                      and potentially other tick-borne pathogens as well.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>IMPORTANCE<\/jats:title>\n                    <jats:p>\n                      Lyme disease (LD) is the most commonly reported tick-borne illness in the U.S. and Europe, and its geographic distribution is continuously expanding worldwide. Though early LD can be treated with antibiotics, chronic LD is recalcitrant to antibiotic treatments and thus requires multiple courses of antibiotic therapy. Currently, there are no human vaccines nor prophylactic antibiotics to prevent LD. As the causative agent of LD,\n                      <jats:italic>Borreliella burgdorferi<\/jats:italic>\n                      has evolved unique metabolic pathways, some of which are specific and essential for its survival and thus present as ideal targets for developing new therapeutics. By using an approach of genetics, biochemistry, structural biology, drug screening, and animal models, this report provides evidence that lactate dehydrogenase can be a potential target for developing genus-specific metabolic inhibitors against\n                      <jats:italic>B. burgdorferi<\/jats:italic>\n                      and potentially other tick-borne pathogens as well.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1128\/mbio.03728-24","type":"journal-article","created":{"date-parts":[[2025,3,20]],"date-time":"2025-03-20T10:23:45Z","timestamp":1742466225000},"update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":11,"title":["Lactate dehydrogenase is the Achilles\u2019 heel of Lyme disease bacterium\n                    <i>Borreliella burgdorferi<\/i>"],"prefix":"10.1128","volume":"16","author":[{"given":"Ching Wooen","family":"Sze","sequence":"first","affiliation":[{"name":"Department of Oral Craniofacial Molecular Biology, Virginia Commonwealth University","place":["Richmond, USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3569-4749","authenticated-orcid":false,"given":"Michael J.","family":"Lynch","sequence":"additional","affiliation":[{"name":"Department of Chemistry and Chemical Biology, Cornell University","place":["Ithaca, USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kai","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Oral Craniofacial Molecular Biology, Virginia Commonwealth University","place":["Richmond, USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David B.","family":"Neau","sequence":"additional","affiliation":[{"name":"Department of Chemistry and Chemical Biology, Cornell University","place":["Ithaca, USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Steven E.","family":"Ealick","sequence":"additional","affiliation":[{"name":"Department of Chemistry and Chemical Biology, Cornell University","place":["Ithaca, USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8234-9991","authenticated-orcid":false,"given":"Brian R.","family":"Crane","sequence":"additional","affiliation":[{"name":"Department of Chemistry and Chemical Biology, Cornell University","place":["Ithaca, USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1872-4870","authenticated-orcid":true,"given":"Chunhao","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Oral Craniofacial Molecular Biology, Virginia Commonwealth University","place":["Richmond, USA"]},{"name":"Department of Microbiology and Immunology, Virginia Commonwealth University","place":["Richmond, USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"235","reference":[{"key":"e_1_3_5_2_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM200107123450207"},{"key":"e_1_3_5_3_2","doi-asserted-by":"publisher","DOI":"10.1089\/vbz.2017.2127"},{"key":"e_1_3_5_4_2","doi-asserted-by":"publisher","DOI":"10.3201\/eid2702.202731"},{"key":"e_1_3_5_5_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.idc.2015.02.010"},{"key":"e_1_3_5_6_2","doi-asserted-by":"publisher","DOI":"10.15585\/mmwr.ss6622a1"},{"key":"e_1_3_5_7_2","doi-asserted-by":"publisher","DOI":"10.21775\/cimb.042.191"},{"key":"e_1_3_5_8_2","doi-asserted-by":"publisher","DOI":"10.1093\/cid\/ciz872"},{"key":"e_1_3_5_9_2","doi-asserted-by":"publisher","DOI":"10.1017\/S0950268806007096"},{"key":"e_1_3_5_10_2","doi-asserted-by":"publisher","DOI":"10.1038\/524406a"},{"key":"e_1_3_5_11_2","doi-asserted-by":"publisher","DOI":"10.1093\/infdis\/jiae202"},{"key":"e_1_3_5_12_2","doi-asserted-by":"publisher","DOI":"10.1080\/14760584.2022.2102484"},{"key":"e_1_3_5_13_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41584-021-00648-5"},{"key":"e_1_3_5_14_2","doi-asserted-by":"publisher","DOI":"10.1038\/nrdp.2016.90"},{"key":"e_1_3_5_15_2","doi-asserted-by":"publisher","DOI":"10.1007\/s12016-021-08906-w"},{"key":"e_1_3_5_16_2","doi-asserted-by":"publisher","DOI":"10.1001\/jama.2023.15358"},{"key":"e_1_3_5_17_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.00883-15"},{"key":"e_1_3_5_18_2","doi-asserted-by":"publisher","DOI":"10.1038\/emi.2015.56"},{"key":"e_1_3_5_19_2","doi-asserted-by":"publisher","DOI":"10.3389\/fmicb.2019.00690"},{"key":"e_1_3_5_20_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.00864-15"},{"key":"e_1_3_5_21_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1600-0463.2010.02615.x"},{"key":"e_1_3_5_22_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0029914"},{"key":"e_1_3_5_23_2","doi-asserted-by":"publisher","DOI":"10.1038\/37551"},{"key":"e_1_3_5_24_2","doi-asserted-by":"publisher","DOI":"10.1046\/j.1365-2958.2000.01698.x"},{"key":"e_1_3_5_25_2","doi-asserted-by":"publisher","DOI":"10.21775\/9781913652616.06"},{"key":"e_1_3_5_26_2","doi-asserted-by":"publisher","DOI":"10.1038\/nmicrobiol.2016.213"},{"key":"e_1_3_5_27_2","doi-asserted-by":"publisher","DOI":"10.1007\/s002030050713"},{"key":"e_1_3_5_28_2","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.biochem.78.072407.102340"},{"key":"e_1_3_5_29_2","volume-title":"Medical microbiology","author":"Jurtshuk J Jr","year":"1996","unstructured":"Jurtshuk J Jr. 1996. Bacterial metabolism. In Baron S (ed), Medical microbiology, 4th ed. University of Texas Medical Branch at Galveston, Galveston, TX.","edition":"4"},{"key":"e_1_3_5_30_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0084625"},{"key":"e_1_3_5_31_2","doi-asserted-by":"publisher","DOI":"10.1042\/bj0760491"},{"key":"e_1_3_5_32_2","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.mi.06.100152.001503"},{"key":"e_1_3_5_33_2","doi-asserted-by":"publisher","DOI":"10.1128\/mr.44.1.106-139.1980"},{"key":"e_1_3_5_34_2","doi-asserted-by":"publisher","DOI":"10.1021\/bi00311a010"},{"key":"e_1_3_5_35_2","doi-asserted-by":"publisher","DOI":"10.1021\/bi00174a042"},{"key":"e_1_3_5_36_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.ppat.1010385"},{"key":"e_1_3_5_37_2","doi-asserted-by":"publisher","DOI":"10.1128\/mr.44.1.83-105.1980"},{"key":"e_1_3_5_38_2","doi-asserted-by":"publisher","DOI":"10.1128\/MMBR.00042-08"},{"key":"e_1_3_5_39_2","doi-asserted-by":"publisher","DOI":"10.1002\/prot.22597"},{"key":"e_1_3_5_40_2","doi-asserted-by":"publisher","DOI":"10.1038\/nsb0394-176"},{"key":"e_1_3_5_41_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M113.458265"},{"key":"e_1_3_5_42_2","doi-asserted-by":"publisher","DOI":"10.1016\/0010-7824(82)90135-4"},{"key":"e_1_3_5_43_2","doi-asserted-by":"publisher","DOI":"10.2174\/0929867324666170209103444"},{"key":"e_1_3_5_44_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejmech.2022.114605"},{"key":"e_1_3_5_45_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2605.1983.tb00328.x"},{"key":"e_1_3_5_46_2","doi-asserted-by":"publisher","DOI":"10.1006\/jmbi.1994.1202"},{"key":"e_1_3_5_47_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.fob.2014.08.006"},{"key":"e_1_3_5_48_2","doi-asserted-by":"publisher","DOI":"10.1039\/fd9929300153:153-62"},{"key":"e_1_3_5_49_2","doi-asserted-by":"publisher","DOI":"10.1006\/jmbi.1994.1318"},{"key":"e_1_3_5_50_2","doi-asserted-by":"publisher","DOI":"10.1128\/JB.01176-10"},{"key":"e_1_3_5_51_2","doi-asserted-by":"publisher","DOI":"10.1128\/JB.00253-12"},{"key":"e_1_3_5_52_2","doi-asserted-by":"publisher","DOI":"10.1128\/mBio.02047-17"},{"key":"e_1_3_5_53_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.ppat.1011752"},{"key":"e_1_3_5_54_2","doi-asserted-by":"publisher","DOI":"10.3390\/pathogens12070962"},{"key":"e_1_3_5_55_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ab.2013.07.003"},{"key":"e_1_3_5_56_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbrc.2024.150721"},{"key":"e_1_3_5_57_2","doi-asserted-by":"publisher","DOI":"10.1111\/jre.12059"},{"key":"e_1_3_5_58_2","doi-asserted-by":"publisher","DOI":"10.1101\/pdb.prot087379"},{"key":"e_1_3_5_59_2","doi-asserted-by":"publisher","DOI":"10.1128\/microbiolspec.MBP-0011-2014"},{"key":"e_1_3_5_60_2","doi-asserted-by":"publisher","DOI":"10.1111\/mmi.12882"},{"key":"e_1_3_5_61_2","doi-asserted-by":"publisher","DOI":"10.1038\/2271098a0"},{"key":"e_1_3_5_62_2","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.02005-14"},{"key":"e_1_3_5_63_2","doi-asserted-by":"publisher","DOI":"10.1128\/JB.00024-11"},{"key":"e_1_3_5_64_2","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.01299-12"},{"key":"e_1_3_5_65_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.1155207"},{"key":"e_1_3_5_66_2","volume-title":"Enterococci: from commensals to leading causes of drug resistant infection","author":"Ramsey M","year":"2014","unstructured":"Ramsey M, Hartke A, Huycke M. 2014. The physiology and metabolism of enterococci. In Gilmore MS, Clewell DB, Ike Y, Shankar N (ed), Enterococci: from commensals to leading causes of drug resistant infection. Massachusetts Eye and Ear Infirmary, Boston, MA."},{"key":"e_1_3_5_67_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cyto.2018.07.021"},{"key":"e_1_3_5_68_2","doi-asserted-by":"publisher","DOI":"10.1128\/JB.01435-13"},{"key":"e_1_3_5_69_2","doi-asserted-by":"publisher","DOI":"10.1128\/mBio.00404-16"},{"key":"e_1_3_5_70_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2958.2009.07015.x"},{"key":"e_1_3_5_71_2","doi-asserted-by":"publisher","DOI":"10.1128\/JB.00571-10"},{"key":"e_1_3_5_72_2","doi-asserted-by":"publisher","DOI":"10.1001\/archderm.1976.01630310005001"},{"key":"e_1_3_5_73_2","doi-asserted-by":"publisher","DOI":"10.2340\/00015555-3386"},{"key":"e_1_3_5_74_2","first-page":"1379","article-title":"Treatment of psoriasis with orally administered 8-methoxypsoralen and long-wavelength ultraviolet radiation","volume":"118","author":"Wasserman GA","year":"1978","unstructured":"Wasserman GA, Llewellyn MW, Ramsay CA, Haberman HF. 1978. Treatment of psoriasis with orally administered 8-methoxypsoralen and long-wavelength ultraviolet radiation. Can Med Assoc J 118:1379\u20131383.","journal-title":"Can Med Assoc J"},{"key":"e_1_3_5_75_2","doi-asserted-by":"publisher","DOI":"10.1001\/archderm.1997.03890480045006"},{"key":"e_1_3_5_76_2","doi-asserted-by":"publisher","DOI":"10.1016\/0005-2787(71)90111-0"},{"key":"e_1_3_5_77_2","doi-asserted-by":"publisher","DOI":"10.1021\/bi00328a015"},{"key":"e_1_3_5_78_2","volume-title":"IARC monographs on the evaluation of carcinogenic risks to humans, no. 100A","author":"IARC Working Group on the Evaluation of Carcinogenic Risks to Humans","year":"2012","unstructured":"IARC Working Group on the Evaluation of Carcinogenic Risks to Humans. 2012. Methoxsalen plus ultraviolet A radiation. In IARC monographs on the evaluation of carcinogenic risks to humans, no. 100A. International Agency for Research on Cancer, Lyon, France."},{"key":"e_1_3_5_79_2","doi-asserted-by":"publisher","DOI":"10.1039\/c19650000309"},{"key":"e_1_3_5_80_2","doi-asserted-by":"publisher","DOI":"10.1021\/np4000763"},{"key":"e_1_3_5_81_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jep.2006.09.022"},{"key":"e_1_3_5_82_2","doi-asserted-by":"publisher","DOI":"10.1021\/np020135d"},{"key":"e_1_3_5_83_2","doi-asserted-by":"publisher","DOI":"10.1021\/jf103610j"},{"key":"e_1_3_5_84_2","doi-asserted-by":"publisher","DOI":"10.1038\/cddis.2014.4"},{"key":"e_1_3_5_85_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.bmcl.2008.10.033"},{"key":"e_1_3_5_86_2","doi-asserted-by":"publisher","DOI":"10.1021\/jf102255u"},{"key":"e_1_3_5_87_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jnutbio.2010.11.002"},{"key":"e_1_3_5_88_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.phymed.2015.09.005"},{"key":"e_1_3_5_89_2","doi-asserted-by":"publisher","DOI":"10.1007\/s12272-011-0603-4"},{"key":"e_1_3_5_90_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ibiod.2011.11.016"},{"key":"e_1_3_5_91_2","doi-asserted-by":"publisher","DOI":"10.1080\/14786419.2018.1512990"},{"key":"e_1_3_5_92_2","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.00871-10"},{"key":"e_1_3_5_93_2","doi-asserted-by":"publisher","DOI":"10.1096\/fj.201901259R"},{"key":"e_1_3_5_94_2","volume-title":"Maestro release 2024-3","author":"Schr\u00f6dinger","year":"2024","unstructured":"Schr\u00f6dinger. 2024. Maestro release 2024-3. Schr\u00f6dinger, LLC, New York, NY."},{"key":"e_1_3_5_95_2","volume-title":"Protein preparation wizard, Epik release 2024-3","author":"Schr\u00f6dinger","year":"2024","unstructured":"Schr\u00f6dinger. 2024. Protein preparation wizard, Epik release 2024-3. Schr\u00f6dinger, LLC, New York, NY."},{"key":"e_1_3_5_96_2","doi-asserted-by":"publisher","DOI":"10.1007\/s10822-013-9644-8"},{"key":"e_1_3_5_97_2","doi-asserted-by":"publisher","DOI":"10.1002\/jcc.540110405"},{"key":"e_1_3_5_98_2","doi-asserted-by":"publisher","DOI":"10.1021\/acs.jctc.1c00302"},{"key":"e_1_3_5_99_2","volume-title":"LigPrep release 2024-3","author":"Schr\u00f6dinger, LLC","year":"2024","unstructured":"Schr\u00f6dinger, LLC. 2024. LigPrep release 2024-3. Schr\u00f6dinger, LLC, New York, NY."},{"key":"e_1_3_5_100_2","doi-asserted-by":"publisher","DOI":"10.1021\/acs.jctc.1c00810"},{"key":"e_1_3_5_101_2","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.00050-13"},{"key":"e_1_3_5_102_2","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.00145-12"}],"container-title":["mBio"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/journals.asm.org\/doi\/pdf\/10.1128\/mbio.03728-24","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.asm.org\/doi\/pdf\/10.1128\/mbio.03728-24","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,4,9]],"date-time":"2025-04-09T09:03:29Z","timestamp":1744189409000},"score":1,"resource":{"primary":{"URL":"https:\/\/journals.asm.org\/doi\/10.1128\/mbio.03728-24"}},"subtitle":[],"editor":[{"given":"Marvin","family":"Whiteley","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"editor"}]}],"short-title":[],"issued":{"date-parts":[[2025,4,9]]},"references-count":101,"journal-issue":{"issue":"4","published-print":{"date-parts":[[2025,4,9]]}},"alternative-id":["10.1128\/mbio.03728-24"],"URL":"https:\/\/doi.org\/10.1128\/mbio.03728-24","relation":{"has-preprint":[{"id-type":"doi","id":"10.1101\/2025.02.07.637162","asserted-by":"object"}]},"ISSN":["2150-7511"],"issn-type":[{"value":"2150-7511","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,4,9]]},"assertion":[{"value":"2024-11-30","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-02-11","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-03-20","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e03728-24"}}