{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,8]],"date-time":"2026-09-08T00:25:17Z","timestamp":1788827117496,"version":"build-2803163510"},"reference-count":57,"publisher":"MDPI AG","issue":"9","license":[{"start":{"date-parts":[[2021,8,26]],"date-time":"2021-08-26T00:00:00Z","timestamp":1629936000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100004396","name":"Thailand Research Fund","doi-asserted-by":"publisher","award":["IRN61W0004"],"award-info":[{"award-number":["IRN61W0004"]}],"id":[{"id":"10.13039\/501100004396","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100012309","name":"Royal Golden Jubilee (RGJ) Ph.D. Programme","doi-asserted-by":"publisher","award":["PhD\/0092\/2557"],"award-info":[{"award-number":["PhD\/0092\/2557"]}],"id":[{"id":"10.13039\/501100012309","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004071","name":"Khon Kaen University","doi-asserted-by":"publisher","award":["RP"],"award-info":[{"award-number":["RP"]}],"id":[{"id":"10.13039\/501100004071","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Pathogens"],"abstract":"<jats:p>Co-infection with the cagA strain of Helicobacter pylori exacerbates the pathology of human liver fluke Opisthorchis viverrini (OV) infection leading to cholangiocarcinoma. However, underlying mechanisms remain unclear. We report a significant increase in cagA-positive and cagA-negative H. pylori in the stomach, blood, bile, and in the OV worms of co-infected Syrian golden hamsters at one hour, three hours, and one month, post-infection, compared to hamsters infected with either OV or H. pylori alone. Except in the worms, H. pylori numbers declined at three months post-infection, particularly in the bile fluid of co-infected animals. Both strains of H. pylori were immunohistochemically detected in the tegument of the worm, as well as in the bile duct epithelium when co-infected with O. viverrine, but not in H. pylori infection alone. Interestingly, only the cagA-positive strain was detected in the gut of the worm. Co-infection between cagA-positive H. pylori and O. viverrini resulted in a more severe biliary pathology and decreased E-cadherin expression in vivo and in vitro than those of the cagA-negative strain. These data suggest that O. viverrini acts as a carrier of cagA-positive H. pylori and co-migrates to the bile ducts, whereas O. viverrini facilitates H. pylori colonization and enhances the biliary pathogenesis and carcinogenesis.<\/jats:p>","DOI":"10.3390\/pathogens10091089","type":"journal-article","created":{"date-parts":[[2021,8,26]],"date-time":"2021-08-26T09:27:57Z","timestamp":1629970077000},"page":"1089","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":15,"title":["Biliary Migration, Colonization, and Pathogenesis of O. viverrini Co-Infected with CagA+ Helicobacter pylori"],"prefix":"10.3390","volume":"10","author":[{"given":"Watcharapol","family":"Suyapoh","sequence":"first","affiliation":[{"name":"Biomedical Sciences Program, Graduate School, Khon Kaen University, Khon Kaen 40002, Thailand"},{"name":"WHO Collaborating Centre for Research and Control of Opisthorchiasis (Southeast Asian Liver Fluke Disease), Faculty of Medicine, Khon Kaen University, Khon Kaen 40002, Thailand"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Janina E. E.","family":"Tirnitz-Parker","sequence":"additional","affiliation":[{"name":"Liver Disease and Regeneration Group, Curtin Medical School, Curtin Health Innovation Research Institute, Curtin University, Perth 6102, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5662-8636","authenticated-orcid":false,"given":"Sirikachorn","family":"Tangkawattana","sequence":"additional","affiliation":[{"name":"WHO Collaborating Centre for Research and Control of Opisthorchiasis (Southeast Asian Liver Fluke Disease), Faculty of Medicine, Khon Kaen University, Khon Kaen 40002, Thailand"},{"name":"Faculty of Veterinary Medicine, Khon Kaen University, Khon Kaen 40002, Thailand"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sutas","family":"Suttiprapa","sequence":"additional","affiliation":[{"name":"WHO Collaborating Centre for Research and Control of Opisthorchiasis (Southeast Asian Liver Fluke Disease), Faculty of Medicine, Khon Kaen University, Khon Kaen 40002, Thailand"},{"name":"Tropical Medicine Graduate Program, Faculty of Medicine, Khon Kaen University, Khon Kaen 40002, Thailand"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8899-5919","authenticated-orcid":false,"given":"Banchob","family":"Sripa","sequence":"additional","affiliation":[{"name":"WHO Collaborating Centre for Research and Control of Opisthorchiasis (Southeast Asian Liver Fluke Disease), Faculty of Medicine, Khon Kaen University, Khon Kaen 40002, Thailand"},{"name":"Tropical Disease Research Center, Department of Pathology, Faculty of Medicine, Khon Kaen University, Khon Kaen 40002, Thailand"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2021,8,26]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"10","DOI":"10.1016\/j.parint.2011.08.014","article-title":"The current status of opisthorchiasis and clonorchiasis in the Mekong Basin","volume":"61","author":"Sithithaworn","year":"2012","journal-title":"Parasitol. Int."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"301","DOI":"10.1002\/jhbp.62","article-title":"Roles of liver fluke infection as risk factor for cholangiocarcinoma","volume":"21","author":"Sithithaworn","year":"2014","journal-title":"J. Hepatobiliary Pancreat. Sci."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"395","DOI":"10.1016\/j.pt.2012.07.006","article-title":"The tumorigenic liver fluke Opisthorchis viverrini\u2014multiple pathways to cancer","volume":"28","author":"Sripa","year":"2013","journal-title":"Trends. Parasitol."},{"key":"ref_4","unstructured":"IARC (1994). Schistosomes, liver flukes and Helicobacter pylori. IARC Monogr. Eval. Carcinog. Risks Hum., 61, 1\u2013241."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"383","DOI":"10.1016\/j.parint.2016.11.016","article-title":"Co-infections with liver fluke and Helicobacter species: A paradigm change in pathogenesis of opisthorchiasis and cholangiocarcinoma?","volume":"66","author":"Sripa","year":"2017","journal-title":"Parasitol. Int."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"4572","DOI":"10.1096\/fj.13-232751","article-title":"Infection with the carcinogenic liver fluke Opisthorchis viverrini modifies intestinal and biliary microbiome","volume":"27","author":"Plieskatt","year":"2013","journal-title":"FASEB J."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"1751","DOI":"10.7314\/APJCP.2015.16.5.1751","article-title":"The carcinogenic liver fluke Opisthorchis viverrini is a reservoir for species of Helicobacter. Asian","volume":"16","author":"Deenonpoe","year":"2015","journal-title":"Pac. J. Cancer. Prev."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"e00009","DOI":"10.1128\/IAI.00009-17","article-title":"Coinfection with Helicobacter pylori and Opisthorchis viverrini enhances the severity of hepatobiliary abnormalities in hamsters","volume":"85","author":"Dangtakot","year":"2017","journal-title":"Infect. Immun."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1038\/srep42744","article-title":"Elevated prevalence of Helicobacter species and virulence factors in opisthorchiasis and associated hepatobiliary disease","volume":"7","author":"Deenonpoe","year":"2017","journal-title":"Sci. Rep."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"177","DOI":"10.1111\/j.1477-2574.2011.00423.x","article-title":"Helicobacter pylori in Thai patients with cholangiocarcinoma and its association with biliary inflammation and proliferation","volume":"14","author":"Boonyanugomol","year":"2012","journal-title":"HPB"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"787","DOI":"10.4269\/ajtmh.1978.27.787","article-title":"Liver changes in hamsters infected with a liver fluke of man, Opisthorchis viverrini","volume":"27","author":"Bhamarapravati","year":"1978","journal-title":"Am. J. Trop. Med. Hyg."},{"key":"ref_12","first-page":"306","article-title":"Migratory pattern of Opisthorchis viverrini in hamsters","volume":"35","author":"Kaewkes","year":"2004","journal-title":"Southeast Asian. J. Trop. Med."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"519","DOI":"10.1007\/s004380050677","article-title":"A stable shuttle vector system for efficient genetic complementation of Helicobacter pylori strains by transformation and conjugation","volume":"257","author":"Heuermann","year":"1998","journal-title":"Mol. Gen. Genet."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"563","DOI":"10.1007\/BF02423452","article-title":"Cloning of the Helicobacter pylori recA gene and functional characterization of its product","volume":"248","author":"Schmitt","year":"1995","journal-title":"Mol. Gen. Genet."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"97","DOI":"10.1111\/j.1349-7006.1998.tb00535.x","article-title":"Induction of Glandular Stomach Cancers in Helicobacter pylori-sensitive Mongolian Gerbils Treated with N-Methyl-N-nitrosourea and N-Methyl-N \u2032\u2032 \u2032 -nitro-N-nitrosoguanidine in Drinking Water","volume":"89","author":"Tatematsu","year":"1998","journal-title":"Jpn. J. Cancer. Res."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"86","DOI":"10.1186\/s12985-017-0752-2","article-title":"Specific and Quantitative Detection of Human Polyomaviruses BKPyV and JCPyV in the Healthy Pakistani Population","volume":"14","author":"Hussain","year":"2017","journal-title":"Virol. J."},{"key":"ref_17","first-page":"4455","article-title":"Purification of Nucleic Acids by Extraction With Phenol:chloroform","volume":"2006","author":"Sambrook","year":"2006","journal-title":"CSH Protoc."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"261","DOI":"10.1016\/S0022-1759(03)00223-0","article-title":"A method for the absolute quantification of cDNA using real-time PCR","volume":"278","author":"Whelan","year":"2003","journal-title":"J. Immunol. Methods"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"191","DOI":"10.1016\/0022-1759(90)90029-U","article-title":"Removal of endotoxin from protein solutions by phase separation using Triton X-114","volume":"132","author":"Aida","year":"1990","journal-title":"J. Immunol. Methods"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"671","DOI":"10.1038\/nmeth.2089","article-title":"NIH Image to ImageJ: 25 years of image analysis","volume":"9","author":"Schneider","year":"2012","journal-title":"Nat. Methods"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"97","DOI":"10.1016\/bs.apar.2018.10.001","article-title":"Update on Pathogenesis of Opisthorchiasis and Cholangiocarcinoma","volume":"102","author":"Sripa","year":"2018","journal-title":"Adv. Parasitol."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"233","DOI":"10.1002\/path.1868","article-title":"Helicobacter infection and gastric neoplasia","volume":"208","author":"Peek","year":"2006","journal-title":"J. Pathol."},{"key":"ref_23","first-page":"258","article-title":"Helicobacter pylori persistence: Biology and disease","volume":"18","author":"Ramirez","year":"2008","journal-title":"Rev. Gastroenterol. Per\u00fa."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"40","DOI":"10.1111\/hel.12256","article-title":"Extragastric diseases and Helicobacter pylori","volume":"20","author":"Franceschi","year":"2015","journal-title":"Helicobacter"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"234","DOI":"10.1038\/nrgastro.2013.243","article-title":"Clinical effects of Helicobacter pylori outside the stomach","volume":"11","author":"Franceschi","year":"2014","journal-title":"Nat. Rev. Gastroenterol. Hepatol."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"851","DOI":"10.1111\/j.1600-0463.2006.apm_425.x","article-title":"Detection of Helicobacter pylori DNA in peripheral blood from patients with peptic ulcer or gastritis","volume":"114","author":"Huang","year":"2006","journal-title":"APMIS"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"1010","DOI":"10.1046\/j.1440-1746.2003.03062.x","article-title":"Of blood and guts: Association between Helicobacter pylori and the gastric microcirculation","volume":"18","author":"Kalia","year":"2003","journal-title":"J. Gastroenterol. Hepatol."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"5395","DOI":"10.3748\/wjg.v16.i43.5395","article-title":"Role of bacteria in carcinogenesis, with special reference to carcinoma of the gallbladder","volume":"16","author":"Nath","year":"2010","journal-title":"World J. Gastroenterol."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"254","DOI":"10.1016\/S1473-3099(08)70066-5","article-title":"Helicobacter Species and Liver Diseases: Association or Causation?","volume":"8","author":"Pellicano","year":"2008","journal-title":"Lancet Infect. Dis."},{"key":"ref_30","doi-asserted-by":"crossref","unstructured":"Mannion, A., Shen, Z., and Fox, J.G. (2018). Comparative genomics analysis to differentiate metabolic and virulence gene potential in gastric versus enterohepatic Helicobacter species. BMC Genom., 19.","DOI":"10.1186\/s12864-018-5171-2"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"822","DOI":"10.1136\/jcp.2004.017087","article-title":"Topographical localisation of cagA positive and cagA negative Helicobacter pylori strains in the gastric mucosa; an in situ hybridisation study","volume":"57","author":"Romo","year":"2004","journal-title":"J. Clin. Pathol."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"385","DOI":"10.1038\/nrmicro3016","article-title":"Life in the Human Stomach: Persistence Strategies of the Bacterial Pathogen Helicobacter pylori","volume":"11","author":"Salama","year":"2013","journal-title":"Nat. Rev. Microbiol."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"373","DOI":"10.1126\/science.279.5349.373","article-title":"Helicobacter pylori adhesin binding fucosylated histo-blood group antigens revealed by retagging","volume":"279","author":"Ilver","year":"1998","journal-title":"Science"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"573","DOI":"10.1126\/science.1069076","article-title":"Helicobacter pylori SabA adhesin in persistent infection and chronic inflammation","volume":"297","author":"Mahdavi","year":"2002","journal-title":"Science"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"4","DOI":"10.1016\/j.bj.2015.06.002","article-title":"Helicobacter pylori infection: An overview of bacterial virulence factors and pathogenesis","volume":"39","author":"Kao","year":"2016","journal-title":"Biomed. J."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"454","DOI":"10.4161\/gmic.27001","article-title":"Signal transduction of Helicobacter pylori during interaction with host cell protein receptors of epithelial and immune cells","volume":"4","author":"Pachathundikandi","year":"2013","journal-title":"Gut. Microbes"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"102050","DOI":"10.1016\/j.parint.2019.102050","article-title":"Identification, recombinant protein production, and functional analysis of a M60-like metallopeptidase, secreted by the liver fluke Opisthorchis viverrini","volume":"75","author":"Binh","year":"2020","journal-title":"Parasitol. Int."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"497","DOI":"10.1038\/icb.2008.37","article-title":"The Immunobiology of Cholangiocytes","volume":"86","author":"Chen","year":"2008","journal-title":"Immunol. Cell Biol."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"269","DOI":"10.1038\/s41575-019-0125-y","article-title":"Cholangiocyte pathobiology","volume":"16","author":"Banales","year":"2019","journal-title":"Nat. Rev. Gastroenterol. Hepatol."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"e12638","DOI":"10.1111\/hel.12638","article-title":"Review: Pathogenesis of Helicobacter pylori Infection","volume":"24","author":"Chmiela","year":"2019","journal-title":"Helicobacter"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"445","DOI":"10.1111\/hel.12301","article-title":"Lipopolysaccharide Structure and Biosynthesis in Helicobacter pylori","volume":"21","author":"Li","year":"2016","journal-title":"Helicobacter"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"616","DOI":"10.1016\/j.parint.2010.09.008","article-title":"Opisthorchis viverrini excretory\/secretory products induce toll-like receptor 4 upregulation and production of interleukin 6 and 8 in cholangiocyte","volume":"59","author":"Ninlawan","year":"2010","journal-title":"Parasitol. Int."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"151","DOI":"10.1016\/j.parint.2011.07.013","article-title":"Novel Carbohydrate Antigen Expression During Development of Opisthorchis Viverrini-Associated Cholangiocarcinoma in Golden Hamster: A Potential Marker for Early Diagnosis","volume":"61","author":"Sawanyawisuth","year":"2012","journal-title":"Parasitol. Int."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"e12516","DOI":"10.1111\/hel.12516","article-title":"Pathogenesis of Helicobacter pylori Infection","volume":"23","author":"Waskito","year":"2018","journal-title":"Helicobacter"},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"159","DOI":"10.1111\/j.1365-3024.2006.00929.x","article-title":"Cytokine Expression in Hamsters Experimentally Infected with Opisthorchis viverrini","volume":"29","author":"Jittimanee","year":"2007","journal-title":"Parasite Immunol."},{"key":"ref_46","doi-asserted-by":"crossref","unstructured":"Won, J., Cho, Y., Lee, D., Jeon, B.Y., Ju, J.W., Chung, S., and Pak, J.H. (2019). Clonorchis sinensis Excretory-Secretory Products Increase Malignant Characteristics of Cholangiocarcinoma Cells in Three-Dimensional Co-Culture with Biliary Ductal Plates. PLoS Pathog., 15.","DOI":"10.1371\/journal.ppat.1007818"},{"key":"ref_47","doi-asserted-by":"crossref","unstructured":"Backert, S., and Tegtmeyer, N. (2017). Type IV Secretion and signal transduction of Helicobacter pylori CagA through interactions with host cell receptors. Toxins, 9.","DOI":"10.3390\/toxins9040115"},{"key":"ref_48","doi-asserted-by":"crossref","unstructured":"Kaur, J., Sawhney, M., DattaGupta, S., Shukla, N.K., Srivastava, A., Walfish, P.G., and Ralhan, R. (2013). Clinical significance of altered expression of \u03b2-catenin and E-cadherin in oral dysplasia and cancer: Potential link with ALCAM expression. PLoS ONE, 8.","DOI":"10.1371\/journal.pone.0067361"},{"key":"ref_49","doi-asserted-by":"crossref","unstructured":"von Zeidler, S.V., Souza Botelho, T.D., Mendon\u00e7a, E.F., and Batista, A.C. (2014). E-cadherin as a potential biomarker of malignant transformation in oral leukoplakia: A retrospective cohort study. BMC Cancer, 17.","DOI":"10.1186\/1471-2407-14-972"},{"key":"ref_50","doi-asserted-by":"crossref","unstructured":"Zhou, D., Guan, W.B., Wang, J.D., Zhang, Y., Gong, W., and Quan, Z.W. (2013). A Comparative Study of clinicopathological features between chronic cholecystitis patients with and without Helicobacter pylori Infection in gallbladder mucosa. PLoS ONE, 8.","DOI":"10.1371\/journal.pone.0070265"},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"591","DOI":"10.1177\/002215540405200504","article-title":"An immunohistochemical study of the expression of adhesion molecules in gallbladder lesions","volume":"52","author":"Choi","year":"2004","journal-title":"J. Histochem. Cytochem."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"8645","DOI":"10.1007\/s13277-014-2087-6","article-title":"Loss of E-cadherin Promotes Migration and Invasion of Cholangiocarcinoma Cells and Serves as a Potential Marker of Metastasis","volume":"35","author":"Techasen","year":"2014","journal-title":"Tumour Biol."},{"key":"ref_53","first-page":"2111","article-title":"Infection with Helicobacter pylori strains possessing cagA is associated with an increased risk of developing adenocarcinoma of the stomach","volume":"55","author":"Blaser","year":"1995","journal-title":"Cancer Res."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"5791","DOI":"10.1073\/pnas.90.12.5791","article-title":"Molecular characterization of the 128-kDa immunodominant antigen of Helicobacter pylori associated with cytotoxicity and duodenal ulcer","volume":"90","author":"Covacci","year":"1993","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"332","DOI":"10.1016\/0140-6736(91)90477-7","article-title":"Mucosal IgA recognition of Helicobacter pylori 120 kda protein, peptic ulceration, and gastric pathology","volume":"338","author":"Crabtree","year":"1991","journal-title":"Lancet"},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"639","DOI":"10.1038\/sj.bjc.6603309","article-title":"CagA-producing Helicobacter pylori and increased risk of gastric cancer: A nested case-control study in Korea","volume":"95","author":"Gwack","year":"2006","journal-title":"Br. J. Cancer"},{"key":"ref_57","first-page":"1548","article-title":"Helicobacter pylori Infection and precancerous lesions of the stomach","volume":"48","author":"Valle","year":"2001","journal-title":"Hepato-Gastroenterol."}],"container-title":["Pathogens"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2076-0817\/10\/9\/1089\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T06:52:44Z","timestamp":1760165564000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2076-0817\/10\/9\/1089"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,8,26]]},"references-count":57,"journal-issue":{"issue":"9","published-online":{"date-parts":[[2021,9]]}},"alternative-id":["pathogens10091089"],"URL":"https:\/\/doi.org\/10.3390\/pathogens10091089","relation":{},"ISSN":["2076-0817"],"issn-type":[{"value":"2076-0817","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,8,26]]}}}