{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,5]],"date-time":"2026-11-05T19:09:37Z","timestamp":1793905777378,"version":"4.8.0"},"reference-count":43,"publisher":"American Society for Microbiology","issue":"15","license":[{"start":{"date-parts":[[2017,8,1]],"date-time":"2017-08-01T00:00:00Z","timestamp":1501545600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.asm.org\/non-commercial-tdm-license"}],"funder":[{"DOI":"10.13039\/100000002","name":"HHS | National Institutes of Health","doi-asserted-by":"publisher","award":["R01AI107159"],"award-info":[{"award-number":["R01AI107159"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"HHS | National Institutes of Health","doi-asserted-by":"publisher","award":["U19AI107792"],"award-info":[{"award-number":["U19AI107792"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["journals.asm.org"],"crossmark-restriction":true},"short-container-title":["J Bacteriol"],"published-print":{"date-parts":[[2017,8]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    Intracellular bacterial pathogens exploit host cell resources to replicate and survive inside the host. Targeting these host systems is one promising approach to developing novel antimicrobials to treat intracellular infections. We show that human macrophage-like cells infected with\n                    <jats:named-content content-type=\"genus-species\">Brucella abortus<\/jats:named-content>\n                    undergo a metabolic shift characterized by attenuated tricarboxylic acid cycle metabolism, reduced amino acid consumption, altered mitochondrial localization, and increased lactate production. This shift to an aerobic glycolytic state resembles the Warburg effect, a change in energy production that is well described in cancer cells and also occurs in activated inflammatory cells.\n                    <jats:named-content content-type=\"genus-species\">B. abortus<\/jats:named-content>\n                    efficiently uses lactic acid as its sole carbon and energy source and requires the ability to metabolize lactate for normal survival in human macrophage-like cells. We demonstrate that chemical inhibitors of host glycolysis and lactate production do not affect\n                    <jats:italic>in vitro<\/jats:italic>\n                    growth of\n                    <jats:named-content content-type=\"genus-species\">B. abortus<\/jats:named-content>\n                    in axenic culture but decrease its survival in the intracellular niche. Our data support a model in which infection shifts host metabolism to a Warburg-like state, and\n                    <jats:named-content content-type=\"genus-species\">B. abortus<\/jats:named-content>\n                    uses this change in metabolism to promote intracellular survival. Pharmacological perturbation of these features of host cell metabolism may be a useful strategy to inhibit infection by intracellular pathogens.\n                  <\/jats:p>\n                  <jats:p>\n                    <jats:bold>IMPORTANCE<\/jats:bold>\n                    <jats:named-content content-type=\"genus-species\">Brucella<\/jats:named-content>\n                    spp. are intracellular bacterial pathogens that cause disease in a range of mammals, including livestock. Transmission from livestock to humans is common and can lead to chronic human disease. Human macrophage-like cells infected with\n                    <jats:named-content content-type=\"genus-species\">Brucella abortus<\/jats:named-content>\n                    undergo a Warburg-like metabolic shift to an aerobic glycolytic state where the host cells produce lactic acid and have reduced amino acid catabolism. We provide evidence that the pathogen can exploit this change in host metabolism to support growth and survival in the intracellular niche. Drugs that inhibit this shift in host cell metabolism inhibit intracellular replication and decrease the survival of\n                    <jats:named-content content-type=\"genus-species\">B. abortus<\/jats:named-content>\n                    in an\n                    <jats:italic>in vitro<\/jats:italic>\n                    infection model; these drugs may be broadly useful therapeutics for intracellular infections.\n                  <\/jats:p>","DOI":"10.1128\/jb.00227-17","type":"journal-article","created":{"date-parts":[[2017,5,30]],"date-time":"2017-05-30T20:30:30Z","timestamp":1496176230000},"update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":79,"title":["Brucella abortus Induces a Warburg Shift in Host Metabolism That Is Linked to Enhanced Intracellular Survival of the Pathogen"],"prefix":"10.1128","volume":"199","author":[{"given":"Daniel M.","family":"Czy\u017c","sequence":"first","affiliation":[{"name":"Howard Taylor Ricketts Laboratory, University of Chicago, Argonne National Laboratory, Lemont, Illinois, USA"},{"name":"Department of Biochemistry and Molecular Biology, University of Chicago, Chicago, Illinois, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jonathan W.","family":"Willett","sequence":"additional","affiliation":[{"name":"Howard Taylor Ricketts Laboratory, University of Chicago, Argonne National Laboratory, Lemont, Illinois, USA"},{"name":"Department of Biochemistry and Molecular Biology, University of Chicago, Chicago, Illinois, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sean","family":"Crosson","sequence":"additional","affiliation":[{"name":"Howard Taylor Ricketts Laboratory, University of Chicago, Argonne National Laboratory, Lemont, Illinois, USA"},{"name":"Department of Biochemistry and Molecular Biology, University of Chicago, Chicago, Illinois, USA"},{"name":"Department of Microbiology, University of Chicago, Chicago, Illinois, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"235","reference":[{"key":"e_1_3_3_2_2","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2014.00420"},{"key":"e_1_3_3_3_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2013.04.005"},{"key":"e_1_3_3_4_2","doi-asserted-by":"publisher","DOI":"10.1038\/cr.2015.68"},{"key":"e_1_3_3_5_2","doi-asserted-by":"publisher","DOI":"10.1085\/jgp.8.6.519"},{"key":"e_1_3_3_6_2","doi-asserted-by":"publisher","DOI":"10.1152\/physrev.00044.2005"},{"key":"e_1_3_3_7_2","doi-asserted-by":"publisher","DOI":"10.1016\/0952-7915(91)90079-G"},{"key":"e_1_3_3_8_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.coi.2015.07.002"},{"key":"e_1_3_3_9_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbamcr.2012.03.005"},{"key":"e_1_3_3_10_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0167486"},{"key":"e_1_3_3_11_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1100126108"},{"key":"e_1_3_3_12_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.R200006200"},{"key":"e_1_3_3_13_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.chom.2013.07.009"},{"key":"e_1_3_3_14_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.chom.2013.07.016"},{"key":"e_1_3_3_15_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.chom.2013.07.010"},{"key":"e_1_3_3_16_2","doi-asserted-by":"publisher","DOI":"10.1007\/s10863-012-9422-7"},{"key":"e_1_3_3_17_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbrc.2004.09.047"},{"key":"e_1_3_3_18_2","doi-asserted-by":"publisher","DOI":"10.1002\/cbic.201300562"},{"key":"e_1_3_3_19_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0021-9258(18)64988-9"},{"key":"e_1_3_3_20_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0018147"},{"key":"e_1_3_3_21_2","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.01998-05"},{"key":"e_1_3_3_22_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.bcp.2015.02.007"},{"key":"e_1_3_3_23_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1462-5822.2006.00741.x"},{"key":"e_1_3_3_24_2","doi-asserted-by":"publisher","DOI":"10.1042\/BST0321070"},{"key":"e_1_3_3_25_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.ppat.1004866"},{"key":"e_1_3_3_26_2","doi-asserted-by":"publisher","DOI":"10.1021\/pr800978p"},{"key":"e_1_3_3_27_2","doi-asserted-by":"publisher","DOI":"10.1128\/JB.01663-14"},{"key":"e_1_3_3_28_2","doi-asserted-by":"publisher","DOI":"10.1099\/00221287-38-1-109"},{"key":"e_1_3_3_29_2","doi-asserted-by":"publisher","DOI":"10.1128\/jb.59.6.777-782.1950"},{"key":"e_1_3_3_30_2","doi-asserted-by":"publisher","DOI":"10.1128\/jb.56.1.17-24.1948"},{"key":"e_1_3_3_31_2","doi-asserted-by":"crossref","first-page":"499","DOI":"10.1152\/physrev.1978.58.2.499","article-title":"Principal substrates of fetal metabolism","volume":"58","author":"Battaglia FC","year":"1978","unstructured":"Battaglia FC Meschia G . 1978. 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