{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,25]],"date-time":"2026-08-25T12:19:21Z","timestamp":1787660361966,"version":"build-2736575974"},"reference-count":39,"publisher":"MDPI AG","issue":"17","license":[{"start":{"date-parts":[[2026,8,25]],"date-time":"2026-08-25T00:00:00Z","timestamp":1787616000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Fondo Nacional de Investigaci\u00f3n Cient\u00edfica y Tecnol\u00f3gica","award":["1261622"],"award-info":[{"award-number":["1261622"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Int. J. Mol. Sci.","IJMS"],"abstract":"<jats:p>Extraintestinal pathogenic Escherichia coli (ExPEC) is among the bacterial pathogens associated with infections of the female and male reproductive tracts, where it may contribute to inflammatory processes and impaired reproductive function. In this context, neutrophils constitute a critical component of host defense through the release of neutrophil extracellular traps (NETs), web-like structures composed of decondensed chromatin, histones, and antimicrobial proteins that capture and eliminate invading microorganisms. However, the interaction between E. coli and NETs is highly dynamic, as the bacterium has evolved immune-evasion mechanisms that facilitate persistence within the host. This raises a critical paradox: NETs may shift from an antimicrobial defense mechanism to a microenvironmental factor that inadvertently favors bacterial persistence and chronic inflammation. This review synthesizes current evidence on the colonization, virulence, and immune-evasion mechanisms of E. coli in the reproductive tract, with particular emphasis on the modulation of NETosis, biofilm formation, and their contribution to antimicrobial resistance. We further discuss the dual role of NETs as an innate immune defense mechanism and, conversely, as a potential contributor to tissue injury, oxidative stress, and chronic inflammation when dysregulated. Understanding the interplay among E. coli, extracellular traps, and antimicrobial resistance provides a valuable conceptual framework for the development of novel therapeutic approaches aimed at limiting bacterial persistence, preserving reproductive function, and addressing the growing global threat of antimicrobial resistance.<\/jats:p>","DOI":"10.3390\/ijms27177608","type":"journal-article","created":{"date-parts":[[2026,8,25]],"date-time":"2026-08-25T11:27:19Z","timestamp":1787657239000},"page":"7608","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Extracellular Traps at the Crossroads of Immune Evasion and Antimicrobial Resistance: The Case of Escherichia coli in the Reproductive Tract"],"prefix":"10.3390","volume":"27","author":[{"given":"Gina","family":"Bertolotto","sequence":"first","affiliation":[{"name":"Center of Excellence in Translational Medicine-Scientific and Technological Bioresource Nucleus (CEMT-BIOREN), Faculty of Medicine, Universidad de La Frontera, Temuco 4780000, Chile"},{"name":"Department of Obstetrics and Gynecology, Faculty of Medicine, Universidad de La Frontera, Temuco 4780000, Chile"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7358-7541","authenticated-orcid":false,"given":"Pamela","family":"Uribe","sequence":"additional","affiliation":[{"name":"Center of Excellence in Translational Medicine-Scientific and Technological Bioresource Nucleus (CEMT-BIOREN), Faculty of Medicine, Universidad de La Frontera, Temuco 4780000, Chile"},{"name":"Department of Internal Medicine, Faculty of Medicine, Universidad de La Frontera, Temuco 4780000, Chile"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0005-7072-843X","authenticated-orcid":false,"given":"B\u00e1rbara","family":"Rosales","sequence":"additional","affiliation":[{"name":"Center of Excellence in Translational Medicine-Scientific and Technological Bioresource Nucleus (CEMT-BIOREN), Faculty of Medicine, Universidad de La Frontera, Temuco 4780000, Chile"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4853-4282","authenticated-orcid":false,"given":"Ra\u00fal","family":"S\u00e1nchez","sequence":"additional","affiliation":[{"name":"Center of Excellence in Translational Medicine-Scientific and Technological Bioresource Nucleus (CEMT-BIOREN), Faculty of Medicine, Universidad de La Frontera, Temuco 4780000, Chile"},{"name":"Department of Preclinical Sciences, Faculty of Medicine, Universidad de La Frontera, Temuco 4780000, Chile"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4840-0508","authenticated-orcid":false,"given":"Fabiola","family":"Zambrano","sequence":"additional","affiliation":[{"name":"Center of Excellence in Translational Medicine-Scientific and Technological Bioresource Nucleus (CEMT-BIOREN), Faculty of Medicine, Universidad de La Frontera, Temuco 4780000, Chile"},{"name":"Department of Preclinical Sciences, Faculty of Medicine, Universidad de La Frontera, Temuco 4780000, Chile"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,8,25]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"2359691","DOI":"10.1080\/19490976.2024.2359691","article-title":"Vaccines against Extraintestinal Pathogenic Escherichia coli (ExPEC): Progress and Challenges","volume":"16","author":"Qiu","year":"2024","journal-title":"Gut Microbes"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"105487","DOI":"10.1016\/j.micpath.2022.105487","article-title":"Bacillus Subtilis Ameliorates Escherichia Coli-Induced Endometritis in Mice via Maintaining Endometrial Barrier and Inhibiting Inflammatory Response","volume":"166","author":"Li","year":"2022","journal-title":"Microb. Pathog."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"1155","DOI":"10.1016\/j.fertnstert.2015.01.044","article-title":"Ability of Escherichia coli to Produce Hemolysis Leads to a Greater Pathogenic Effect on Human Sperm","volume":"103","author":"Boguen","year":"2015","journal-title":"Fertil. Steril."},{"key":"ref_4","doi-asserted-by":"crossref","unstructured":"Ricci, S., De Giorgi, S., Lazzeri, E., Luddi, A., Rossi, S., Piomboni, P., De Leo, V., and Pozzi, G. (2018). Impact of Asymptomatic Genital Tract Infections on In Vitro Fertilization (IVF) Outcome. PLoS ONE, 13.","DOI":"10.1371\/journal.pone.0207684"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"2223","DOI":"10.1007\/s10815-020-01883-7","article-title":"Increase of Leucocyte-Derived Extracellular Traps (ETs) in Semen Samples from Human Acute Epididymitis Patients-a Pilot Study","volume":"37","author":"Zambrano","year":"2020","journal-title":"J. Assist. Reprod. Genet."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"1532","DOI":"10.1126\/science.1092385","article-title":"Neutrophil Extracellular Traps Kill Bacteria","volume":"303","author":"Brinkmann","year":"2004","journal-title":"Science"},{"key":"ref_7","doi-asserted-by":"crossref","unstructured":"Li, H., Liu, L., Wang, J., and Zhao, W. (2023). The Emerging Role of Neutrophil Extracellular Traps in Endometritis. Front. Immunol., 14.","DOI":"10.3389\/fimmu.2023.1153851"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"892","DOI":"10.1016\/j.resmic.2017.02.002","article-title":"The Role of Escherichia coli in Reproductive Health: State of the Art","volume":"168","author":"Cools","year":"2017","journal-title":"Res. Microbiol."},{"key":"ref_9","unstructured":"(2026, June 13). World Health Organization Antimicrobial Resistance. Available online: https:\/\/www.who.int\/news-room\/fact-sheets\/detail\/antimicrobial-resistance."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"2683","DOI":"10.1093\/humrep\/dep343","article-title":"The International Committee for Monitoring Assisted Reproductive Technology (ICMART) and the World Health Organization (WHO) Revised Glossary on ART Terminology, 2009","volume":"24","author":"Adamson","year":"2009","journal-title":"Hum. Reprod."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"3","DOI":"10.1016\/j.ejogrb.2008.03.009","article-title":"Genital Tract Infections and Infertility","volume":"140","author":"Pellati","year":"2008","journal-title":"Eur. J. Obstet. Gynecol. Reprod. Biol."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"57","DOI":"10.1007\/s11010-020-03833-4","article-title":"Staphylococcal Infections and Infertility: Mechanisms and Management","volume":"474","author":"Dutta","year":"2020","journal-title":"Mol. Cell. Biochem."},{"key":"ref_13","first-page":"68","article-title":"Frecuencia, Factores de Riesgo y Colonizaci\u00f3n Vaginal Por Escherichia coli","volume":"72","author":"Rosas","year":"2004","journal-title":"Ginecol. Obstet. Mex."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"381","DOI":"10.4067\/S0716-10182013000400005","article-title":"An\u00e1lisis Gen\u00e9tico y Propiedades Virulentas de Cepas de Escherichia coli Aisladas Desde Infecci\u00f3n Vaginal","volume":"30","author":"Lobos","year":"2013","journal-title":"Rev. Chil. Infectol."},{"key":"ref_15","doi-asserted-by":"crossref","unstructured":"O\u2019Brien, V.P., Gilbert, N.M., Lebratti, T., Agarwal, K., Foster, L., Shin, H., and Lewis, A.L. (2019). Low-Dose Inoculation of Escherichia coli Achieves Robust Vaginal Colonization and Results in Ascending Infection Accompanied by Severe Uterine Inflammation in Mice. PLoS ONE, 14.","DOI":"10.1371\/journal.pone.0219941"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"3481","DOI":"10.1038\/s41467-021-23881-8","article-title":"TcpC Inhibits Neutrophil Extracellular Trap Formation by Enhancing Ubiquitination Mediated Degradation of Peptidylarginine Deiminase 4","volume":"12","author":"Ou","year":"2021","journal-title":"Nat. Commun."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"100824","DOI":"10.1016\/j.nmni.2020.100824","article-title":"Uropathogenic Escherichia coli in the High Vaginal Swab Samples of Fertile and Infertile Women: Virulence Factors, O-Serogroups, and Phenotyping and Genotyping Characterization of Antibiotic Resistance","volume":"38","author":"Jafariaskari","year":"2020","journal-title":"New Microbes New Infect."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"4","DOI":"10.21836\/PEM20120101","article-title":"Cytokines and Neutrophil Extracellular Traps in the Equine Endometrium: Friends or Foes?","volume":"28","author":"Skarzynski","year":"2012","journal-title":"Pferdeheilkunde Equine Med."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"51","DOI":"10.1016\/j.jri.2005.06.003","article-title":"Bacterial Infection and Semen Quality","volume":"67","author":"Kurpisz","year":"2005","journal-title":"J. Reprod. Immunol."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"33","DOI":"10.5653\/cerm.2020.04161","article-title":"A Comparison of Different O-Antigen Serogroups of Escherichia coli in Semen Samples of Fertile and Infertile Men","volume":"49","author":"Nabi","year":"2022","journal-title":"Clin. Exp. Reprod. Med."},{"key":"ref_21","first-page":"322","article-title":"The Impact of Bacteriospermia on Sperm Survival and DNA Fragmentation in Subfertile Men","volume":"15","author":"Samantaray","year":"2025","journal-title":"Asian J. Res. Pharm. Sci."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"1405","DOI":"10.1016\/j.mucimm.2025.10.001","article-title":"Epididymitis Promotes Formation of Tertiary Lymphoid Organs in the Cauda Epididymidis","volume":"18","author":"Hasan","year":"2025","journal-title":"Mucosal Immunol."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"e13743","DOI":"10.1111\/and.13743","article-title":"The Role of Infections and Leukocytes in Male Infertility","volume":"53","author":"Henkel","year":"2021","journal-title":"Andrologia"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"271","DOI":"10.1111\/j.1365-2605.1996.tb00475.x","article-title":"Influence of Escherichia coli on Motility Parameters of Human Spermatozoa In Vitro","volume":"19","author":"Diemer","year":"1996","journal-title":"Int. J. Androl."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"33","DOI":"10.1016\/j.micpath.2014.03.010","article-title":"Spermagglutinating Escherichia coli and Its Role in Infertility: Invivostudy","volume":"69\u201370","author":"Kaur","year":"2014","journal-title":"Microb. Pathog."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"203","DOI":"10.1155\/S1064744901000333","article-title":"Virulence Factors of Escherichia coli Isolated from Female Reproductive Tract Infections and Neonatal Sepsis","volume":"9","author":"Cook","year":"2001","journal-title":"Infect. Dis. Obstet. Gynecol."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"10","DOI":"10.1186\/s13099-019-0290-0","article-title":"Virulence Factors, Prevalence and Potential Transmission of Extraintestinal Pathogenic Escherichia coli Isolated from Different Sources: Recent Reports","volume":"11","author":"Sarowska","year":"2019","journal-title":"Gut Pathog."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"123","DOI":"10.1038\/nrmicro818","article-title":"Pathogenic Escherichia coli","volume":"2","author":"Kaper","year":"2004","journal-title":"Nat. Rev. Microbiol."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"209","DOI":"10.1016\/j.jmii.2024.12.007","article-title":"O-Antigen of Uropathogenic Escherichia coli Is Required for Induction of Neutrophil Extracellular Traps","volume":"58","author":"Lin","year":"2025","journal-title":"J. Microbiol. Immunol. Infect."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"104640","DOI":"10.1016\/j.cellimm.2022.104640","article-title":"Neutrophil Extracellular Traps: Modulation Mechanisms by Pathogens","volume":"382","author":"Gonzalez","year":"2022","journal-title":"Cell. Immunol."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"773","DOI":"10.1083\/jcb.201203170","article-title":"Neutrophil Extracellular Traps: Is Immunity the Second Function of Chromatin?","volume":"198","author":"Brinkmann","year":"2012","journal-title":"J. Cell Biol."},{"key":"ref_32","doi-asserted-by":"crossref","unstructured":"Malaluang, P., Wil\u00e9n, E., Lindahl, J., Hansson, I., and Morrell, J.M. (2021). Antimicrobial Resistance in Equine Reproduction. Animals, 11.","DOI":"10.3390\/ani11113035"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"59","DOI":"10.1095\/biolreprod.113.110379","article-title":"Structural and Functional Integrity of Spermatozoa is Compromised as a Consequence of Acute Uropathogenic E. Coli-Associated Epididymitis","volume":"89","author":"Lang","year":"2013","journal-title":"Biol. Reprod."},{"key":"ref_34","doi-asserted-by":"crossref","unstructured":"Shen, W., Ma, X., Shao, D., Wu, X., Wang, S., Zheng, J., Lv, Y., Ding, X., Ma, B., and Yan, Z. (2022). Neutrophil Extracellular Traps Mediate Bovine Endometrial Epithelial Cell Pyroptosis in Dairy Cows with Endometritis. Int. J. Mol. Sci., 23.","DOI":"10.3390\/ijms232214013"},{"key":"ref_35","doi-asserted-by":"crossref","unstructured":"Han, Z., Wei, Z., Cui, Z., Zhang, S., An, X., Yang, Z., and Li, Z. (Res. Sq., 2025). Mouse Sperms Trigger Neutrophil Extracellular Traps Which Impair Sperm Motility and Entangle with the Embryo, Res. Sq., preprint.","DOI":"10.21203\/rs.3.rs-6456943\/v1"},{"key":"ref_36","doi-asserted-by":"crossref","unstructured":"Baz, A.A., Hao, H., Lan, S., Li, Z., Liu, S., Chen, S., and Chu, Y. (2024). Neutrophil Extracellular Traps in Bacterial Infections and Evasion Strategies. Front. Immunol., 15.","DOI":"10.3389\/fimmu.2024.1357967"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"1205","DOI":"10.1038\/s41564-026-02283-w","article-title":"Identification of Transporter-Dependent Capsular Loci Associated with the Invasive Potential of Escherichia coli","volume":"11","author":"Gladstone","year":"2026","journal-title":"Nat. Microbiol."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"27","DOI":"10.1038\/s44259-024-00046-3","article-title":"Mechanisms of Antimicrobial Resistance in Biofilms","volume":"2","author":"Liu","year":"2024","journal-title":"npj Antimicrob. Resist."},{"key":"ref_39","doi-asserted-by":"crossref","unstructured":"Aziz, W., Sultana, H., Kumar, V., and Tyagi, A. (2025). The Relationship Between NETosis and Biofilm Formation in Chronic Infections. Biomolecules, 15.","DOI":"10.3390\/biom15121692"}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/27\/17\/7608\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,8,25]],"date-time":"2026-08-25T11:28:22Z","timestamp":1787657302000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/27\/17\/7608"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,8,25]]},"references-count":39,"journal-issue":{"issue":"17","published-online":{"date-parts":[[2026,9]]}},"alternative-id":["ijms27177608"],"URL":"https:\/\/doi.org\/10.3390\/ijms27177608","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,8,25]]}}}