{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T11:03:50Z","timestamp":1785409430876,"version":"3.56.0"},"reference-count":57,"publisher":"American Society for Microbiology","issue":"11","license":[{"start":{"date-parts":[[2025,11,4]],"date-time":"2025-11-04T00:00:00Z","timestamp":1762214400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2025,11,4]],"date-time":"2025-11-04T00:00:00Z","timestamp":1762214400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.asm.org\/non-commercial-tdm-license"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"crossref","award":["82372284"],"award-info":[{"award-number":["82372284"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":["journals.asm.org"],"crossmark-restriction":true},"short-container-title":["Microbiol Spectr"],"published-print":{"date-parts":[[2025,11,4]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title\/>\n                    <jats:p>\n                      <jats:italic toggle=\"yes\">Chlamydia,<\/jats:italic>\n                      an obligate intracellular parasite, depends entirely on host cells for energy and biosynthesis while exerting pathogenic effects through its virulence factors.\n                      <jats:italic toggle=\"yes\">Chlamydia muridarum<\/jats:italic>\n                      (\n                      <jats:italic toggle=\"yes\">Cm<\/jats:italic>\n                      ), an alternative model strain to\n                      <jats:italic toggle=\"yes\">Chlamydia trachomatis<\/jats:italic>\n                      (\n                      <jats:italic toggle=\"yes\">Ct<\/jats:italic>\n                      ), modulates cellular metabolism to enhance its survival and pathogenicity during infection. We found that TC0668, a crucial\n                      <jats:italic toggle=\"yes\">Cm<\/jats:italic>\n                      virulence protein associated with fallopian tube lesions in infected mice, induces a hypermetabolic state in host cells upon\n                      <jats:italic toggle=\"yes\">Cm<\/jats:italic>\n                      stimulation. This results in alterations in glucose consumption, mitochondrial TCA cycle activity, aerobic glycolysis, and intracellular ATP levels. Specifically, infection with the\n                      <jats:italic toggle=\"yes\">Cm<\/jats:italic>\n                      TC0668\n                      <jats:sup>wt<\/jats:sup>\n                      strain in HeLa and HUVEC cells led to the activation of PI3K (p110) and substantial phosphorylation of AKT at S473. This activation was significantly reduced by LY-294002, a potent PI3K\/AKT pathway inhibitor, which led to decreased glucose consumption and ATP levels in HUVECs. However, in HeLa cells, inhibition of the pathway primarily affected GLUT1 expression and ATP levels without impacting glucose consumption. These findings underscore the pivotal role of PI3K\/AKT signaling in regulating cellular glycometabolism under the influence of the TC0668 protein during\n                      <jats:italic toggle=\"yes\">Cm<\/jats:italic>\n                      infection.\n                    <\/jats:p>\n                    <jats:sec>\n                      <jats:title>IMPORTANCE<\/jats:title>\n                      <jats:p>\n                        Previous studies have identified that TC0668, as a virulence factor involved in the formation of fallopian tube hydrosalpinx caused by\n                        <jats:italic toggle=\"yes\">Chlamydia muridarum<\/jats:italic>\n                        (\n                        <jats:italic toggle=\"yes\">Cm<\/jats:italic>\n                        ), is primarily involved in metabolic processes, cellular processes, and biological regulation, and there are notable differences in PI3K activation and AKT phosphorylation induced by\n                        <jats:italic toggle=\"yes\">Cm tc0668<\/jats:italic>\n                        single-gene strains. However, the relationship between TC0668\u2019s influence on\n                        <jats:italic toggle=\"yes\">Cm<\/jats:italic>\n                        -regulated glycometabolism and the activation of the PI3K\/AKT pathway remains unclear. Our study established a vitro cell infection model of\n                        <jats:italic toggle=\"yes\">Cm<\/jats:italic>\n                        using HeLa cells and HUVEC cells, and employed techniques such as Western blotting to reveal a novel mechanism of TC0668 in enhancing the pathogenicity of\n                        <jats:italic toggle=\"yes\">Cm<\/jats:italic>\n                        by regulating host glycometabolism. The study advances our understanding of intracellular pathogen-host interactions and provides novel therapeutic strategies for\n                        <jats:italic toggle=\"yes\">Chlamydia<\/jats:italic>\n                        infections.\n                      <\/jats:p>\n                    <\/jats:sec>\n                  <\/jats:sec>","DOI":"10.1128\/spectrum.03051-24","type":"journal-article","created":{"date-parts":[[2025,10,13]],"date-time":"2025-10-13T13:59:42Z","timestamp":1760363982000},"update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":1,"title":["The influence of TC0668 on glycometabolism modulation in\n                    <i>Chlamydia muridarum<\/i>\n                    -infected host cells"],"prefix":"10.1128","volume":"13","author":[{"ORCID":"https:\/\/orcid.org\/0009-0003-2769-193X","authenticated-orcid":false,"given":"Nanyan","family":"Yu","sequence":"first","affiliation":[{"id":[{"id":"https:\/\/ror.org\/03mqfn238","id-type":"ROR","asserted-by":"publisher"}],"name":"Institute of Pathogenic Biology, Hunan Provincial Key Laboratory for Special Pathogens Prevention and Control, Hunan Province Cooperative Innovation Center for Molecular Target New Drug Study, Hengyang Medical School, University of South China","place":["Hengyang, China"]},{"name":"Department of Laboratory Medicine, Yunnan Provincial Hospital of Traditional Chinese Medicine","place":["Kunming, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xuan","family":"Chen","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/03mqfn238","id-type":"ROR","asserted-by":"publisher"}],"name":"Institute of Pathogenic Biology, Hunan Provincial Key Laboratory for Special Pathogens Prevention and Control, Hunan Province Cooperative Innovation Center for Molecular Target New Drug Study, Hengyang Medical School, University of South China","place":["Hengyang, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wenjing","family":"Yang","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/03mqfn238","id-type":"ROR","asserted-by":"publisher"}],"name":"Institute of Pathogenic Biology, Hunan Provincial Key Laboratory for Special Pathogens Prevention and Control, Hunan Province Cooperative Innovation Center for Molecular Target New Drug Study, Hengyang Medical School, University of South China","place":["Hengyang, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yang","family":"Zhou","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/03mqfn238","id-type":"ROR","asserted-by":"publisher"}],"name":"Institute of Pathogenic Biology, Hunan Provincial Key Laboratory for Special Pathogens Prevention and Control, Hunan Province Cooperative Innovation Center for Molecular Target New Drug Study, Hengyang Medical School, University of South China","place":["Hengyang, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuchen","family":"Hu","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/03mqfn238","id-type":"ROR","asserted-by":"publisher"}],"name":"Institute of Pathogenic Biology, Hunan Provincial Key Laboratory for Special Pathogens Prevention and Control, Hunan Province Cooperative Innovation Center for Molecular Target New Drug Study, Hengyang Medical School, University of South China","place":["Hengyang, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhou","family":"Zhou","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/03mqfn238","id-type":"ROR","asserted-by":"publisher"}],"name":"Institute of Pathogenic Biology, Hunan Provincial Key Laboratory for Special Pathogens Prevention and Control, Hunan Province Cooperative Innovation Center for Molecular Target New Drug Study, Hengyang Medical School, University of South China","place":["Hengyang, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"235","reference":[{"key":"e_1_3_4_2_2","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.mi.34.100180.001441"},{"key":"e_1_3_4_3_2","doi-asserted-by":"publisher","DOI":"10.1080\/21505594.2024.2351234"},{"key":"e_1_3_4_4_2","doi-asserted-by":"publisher","DOI":"10.3390\/microorganisms7050140"},{"key":"e_1_3_4_5_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M117.797209"},{"key":"e_1_3_4_6_2","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.00545-20"},{"key":"e_1_3_4_7_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbrc.2017.11.005"},{"key":"e_1_3_4_8_2","doi-asserted-by":"publisher","DOI":"10.20135\/j.issn.1006-8147.2016.06.025"},{"key":"e_1_3_4_9_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbabio.2020.148276"},{"key":"e_1_3_4_10_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.chom.2018.04.002"},{"key":"e_1_3_4_11_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ygeno.2015.03.001"},{"key":"e_1_3_4_12_2","doi-asserted-by":"publisher","DOI":"10.1111\/cmi.12962"},{"key":"e_1_3_4_13_2","doi-asserted-by":"publisher","DOI":"10.1038\/nrc2715"},{"key":"e_1_3_4_14_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.273.12.7052"},{"key":"e_1_3_4_15_2","doi-asserted-by":"publisher","DOI":"10.1016\/s1286-4579(01)01504-0"},{"key":"e_1_3_4_16_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.celrep.2014.10.004"},{"key":"e_1_3_4_17_2","doi-asserted-by":"publisher","DOI":"10.1038\/ncomms6201"},{"key":"e_1_3_4_18_2","doi-asserted-by":"publisher","DOI":"10.3389\/fmicb.2019.02553"},{"key":"e_1_3_4_19_2","doi-asserted-by":"publisher","DOI":"10.1128\/jb.104.3.1189-1196.1970"},{"key":"e_1_3_4_20_2","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.01171-15"},{"key":"e_1_3_4_21_2","doi-asserted-by":"publisher","DOI":"10.1186\/s12866-015-0498-1"},{"key":"e_1_3_4_22_2","doi-asserted-by":"publisher","DOI":"10.3389\/fmicb.2018.03269"},{"key":"e_1_3_4_23_2","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.73.4.1939-1946.2005"},{"key":"e_1_3_4_24_2","doi-asserted-by":"publisher","DOI":"10.7554\/eLife.12703"},{"key":"e_1_3_4_25_2","doi-asserted-by":"publisher","DOI":"10.3390\/ijms21114086"},{"key":"e_1_3_4_26_2","doi-asserted-by":"publisher","DOI":"10.1093\/femspd\/ftx108"},{"key":"e_1_3_4_27_2","doi-asserted-by":"publisher","DOI":"10.1038\/ncb2522"},{"key":"e_1_3_4_28_2","doi-asserted-by":"publisher","DOI":"10.7554\/eLife.76721"},{"key":"e_1_3_4_29_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.vetmic.2020.108960"},{"key":"e_1_3_4_30_2","doi-asserted-by":"publisher","DOI":"10.2147\/OTT.S208848"},{"key":"e_1_3_4_31_2","doi-asserted-by":"publisher","DOI":"10.1007\/s10863-006-9052-z"},{"key":"e_1_3_4_32_2","doi-asserted-by":"publisher","DOI":"10.1007\/s00430-004-0223-4"},{"key":"e_1_3_4_33_2","doi-asserted-by":"publisher","DOI":"10.21037\/apm-21-1502"},{"key":"e_1_3_4_34_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cyto.2018.05.039"},{"key":"e_1_3_4_35_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.1160809"},{"key":"e_1_3_4_36_2","doi-asserted-by":"publisher","DOI":"10.1080\/15384101.2019.1618125"},{"key":"e_1_3_4_37_2","doi-asserted-by":"publisher","DOI":"10.1007\/s10555-019-09792-7"},{"key":"e_1_3_4_38_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cmet.2014.03.009"},{"key":"e_1_3_4_39_2","doi-asserted-by":"publisher","DOI":"10.3389\/fcimb.2017.00499"},{"key":"e_1_3_4_40_2","doi-asserted-by":"publisher","DOI":"10.1099\/00221287-148-12-3955"},{"key":"e_1_3_4_41_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.mito.2020.05.005"},{"key":"e_1_3_4_42_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.semcancer.2019.06.002"},{"key":"e_1_3_4_43_2","doi-asserted-by":"publisher","DOI":"10.3892\/ol.2017.6038"},{"key":"e_1_3_4_44_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cmet.2006.04.005"},{"key":"e_1_3_4_45_2","doi-asserted-by":"publisher","DOI":"10.1152\/ajpheart.00523.2020"},{"key":"e_1_3_4_46_2","doi-asserted-by":"publisher","DOI":"10.3892\/mmr.2020.11416"},{"key":"e_1_3_4_47_2","doi-asserted-by":"publisher","DOI":"10.3892\/ijo.2020.5040"},{"key":"e_1_3_4_48_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41568-019-0216-7"},{"key":"e_1_3_4_49_2","doi-asserted-by":"publisher","DOI":"10.1007\/s12094-019-02187-8"},{"key":"e_1_3_4_50_2","doi-asserted-by":"publisher","DOI":"10.1097\/MPA.0b013e3181735ccb"},{"key":"e_1_3_4_51_2","doi-asserted-by":"publisher","DOI":"10.1042\/BCJ20190888"},{"key":"e_1_3_4_52_2","doi-asserted-by":"publisher","DOI":"10.1136\/thoraxjnl-2019-213571"},{"key":"e_1_3_4_53_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41419-020-2650-6"},{"key":"e_1_3_4_54_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jmb.2017.07.009"},{"key":"e_1_3_4_55_2","doi-asserted-by":"publisher","DOI":"10.1210\/en.2012-1558"},{"key":"e_1_3_4_56_2","doi-asserted-by":"publisher","DOI":"10.2147\/OTT.S233031"},{"key":"e_1_3_4_57_2","doi-asserted-by":"publisher","DOI":"10.1097\/CAD.0000000000000968"},{"key":"e_1_3_4_58_2","doi-asserted-by":"publisher","DOI":"10.1128\/microbiolspec.bai-0012-2019"}],"container-title":["Microbiology Spectrum"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/journals.asm.org\/doi\/pdf\/10.1128\/spectrum.03051-24","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.asm.org\/doi\/pdf\/10.1128\/spectrum.03051-24","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,11,4]],"date-time":"2025-11-04T14:08:18Z","timestamp":1762265298000},"score":1,"resource":{"primary":{"URL":"https:\/\/journals.asm.org\/doi\/10.1128\/spectrum.03051-24"}},"subtitle":[],"editor":[{"given":"Simone","family":"Filardo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"editor"}]}],"short-title":[],"issued":{"date-parts":[[2025,11,4]]},"references-count":57,"journal-issue":{"issue":"11","published-print":{"date-parts":[[2025,11,4]]}},"alternative-id":["10.1128\/spectrum.03051-24"],"URL":"https:\/\/doi.org\/10.1128\/spectrum.03051-24","relation":{},"ISSN":["2165-0497"],"issn-type":[{"value":"2165-0497","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,11,4]]},"assertion":[{"value":"2024-11-25","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-09-12","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-10-13","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e03051-24"}}