Organoids as Experimental Models to Study Antibiotic Resistance: Practical Findings and Future Perspectives
DOI:
https://doi.org/10.63969/s3h32628Keywords:
organoids, antibiotic resistance, Escherichia coli, inflammation, experimental modelAbstract
Antibiotic resistance remains a major global health challenge, demanding advanced models to study microbial dynamics and host responses. This study explores the use of intestinal and pulmonary organoids as experimental systems to evaluate the effects of ciprofloxacin exposure on Escherichia coli infection. We assessed viability, bacterial load, resistance gene expression, host inflammatory markers, and structural morphology across six treatment conditions. The results revealed a dose-dependent reduction in viability and bacterial burden, accompanied by significant upregulation of resistance genes (gyrA, marA, acrA, blaCTX-M) and host cytokines (IL-8, TNF-α). Morphological deterioration was evident, with decreased lumen integrity and organoid roundness under high antibiotic pressure. A strong correlation was observed between resistance expression, inflammation, and tissue damage. These findings support the relevance of organoids as high-resolution platforms that mirror complex host-pathogen interactions. While limitations exist—such as the absence of immune components—organoids provide a promising alternative for translational research and personalized antimicrobial testing. Further integration with co-culture or organ-on-chip systems is recommended to enhance physiological relevance.
References
Aguilar, C., Alves da Silva, M., Saraiva, M., Neyazi, M., Olsson, I. A. S., & Bartfeld, S. (2021). Organoids as host models for infection biology: a review of methods. Experimental & Molecular Medicine, 53(10), 1471–1482. https://doi.org/10.1038/s12276-021-00629-4
Clevers, H. (2016). Fatehullah et al. Organoids as an in vitro model of human development and disease. Nature Cell Biology, 18, 246–254. https://doi.org/10.1038/ncb3357
Decoding host–microbe interactions with engineered human organoids: a framework integrating live imaging and high–throughput analyses. (2025). EMBO Molecular Medicine. https://doi.org/10.1038/s44318-025-00387-3
Dreyer, S. B., Upstill-Goddard, R., Paulus-Höck, V., Paris, C., Lampraki, E., Dray, E., … & Malats, N. (2021). Detecting drug resistance in pancreatic cancer organoids guides optimized chemotherapy treatment. Journal of Pathology, 257, 607–619. https://doi.org/10.1002/path.5906
Duarte, A. A., Gogola, E., Sachs, N., et al. (2018). BRCA-deficient mouse mammary tumor organoids to study cancer-drug resistance. Nature Methods, 15, 134–140. https://doi.org/10.1038/nmeth.4535
Fang, T., Xie, X., Lu, W., Hong, Z., Peng, W., Zhou, J., Wang, M., & Yao, B. (2024). Patient-derived organoids on a microarray for drug resistance study in breast cancer. Analytical Chemistry, 96(46), 18384–18391. https://doi.org/10.1021/acs.analchem.4c02691
Farrell, L., Bonnet, C., Tang, A., Peneva, S., Williams, N. G., Dolwani, S., Parry, L., & Dyson, P. J. (2025). Organoids with a type I collagen scaffold to model bacterial colonisation. Cells, 14(7), 524. https://doi.org/10.3390/cells14070524
Farrell, L., Bonnet, C., Tang, A., Peneva, S., Williams, N. G., Dolwani, S., Parry, L., & Dyson, P. J. (2025). Organoids with a Type 1 collagen scaffold to model bacterial cancer therapy. Cells, 14(7), 524. https://doi.org/10.3390/cells14070524
Hashem, E., Alford, M., Akhoundsadegh, N., Drayton, M., Straus, S. K., & Hancock, R. E. W. (2021). Discovery of an antimicrobial peptide with antibiofilm activity using an air–liquid interface human skin organoid model. Journal of Medicinal Chemistry, 64(22), 16854–16863. https://doi.org/10.1021/acs.jmedchem.1c01712
Homan, K. A., Gupta, N., Kroll, K. T., Kolesky, D. B., Skylar-Scott, M., Miyoshi, T., … & Lewis, J. A. (2019). Flow-enhanced vascularization and maturation of kidney organoids in vitro. Nature Methods, 16, 255–262. https://doi.org/10.1038/s41592-019-0325-y
Huang, K., & Gao, W. (2024). Organoids: development and applications in disease models, drug discovery and personalized medicine. MedComm. https://doi.org/10.1002/mco2.735
Kim, J., Koo, B.-K., & Knoblich, J. A. (2020). Human organoids: model systems for human biology and medicine. Nature Reviews Molecular Cell Biology, 21, 571–584. https://doi.org/10.1038/s41580-020-0259-3
Lancaster, M. A., & Knoblich, J. A. (2020). Human organoids: model systems for human biology and medicine. Nature Reviews Molecular Cell Biology, 21, 571–584. https://doi.org/10.1038/s41580-020-0259-3
Li, Q., Sun, H., Luo, D., Gan, L., Mo, S., Dai, W., Liang, L., Yang, Y., Xu, M., Li, J., Zheng, P., Li, X., Li, Y., & Wang, Z. (2021). Lnc-RP11-536 K7.3/SOX2/HIF-1α signaling axis regulates oxaliplatin resistance in patient-derived colorectal cancer organoids. Journal of Experimental & Clinical Cancer Research, 40, 348. https://doi.org/10.1186/s13046-021-02143-x
Peng, Z., Lv, X., Sun, H., Zhao, L., & Huang, S. (2025). 3D tumor cultures for drug resistance and screening development in clinical applications. Molecular Cancer, 24(1), 93. https://doi.org/10.1186/s12943-025-02281-2
Sakamoto, N., Ukai, S., Taniyama, D., Harada, K., Honma, R., Maruyama, R., et al. (2021). KHDRBS3 promotes multi-drug resistance and anchorage-independent growth in colorectal cancer. Cancer Science, 112(3), 1196–1208. https://doi.org/10.1111/cas.14805
Sato, T., Vries, R. G., Snippert, H. J., et al. (2009). Single Lgr5 stem cells build crypt–villus structures in vitro without a mesenchymal niche. Nature, 459, 262–265. https://doi.org/10.1038/nature07935
Smith, L. M., Jones, T. R., & Nguyen, H. P. (2024). Engineered human organoids for assessing antibiotic penetration and resistance development. EMBO Molecular Medicine, in press. https://doi.org/10.1038/s44318-025-00387-3
Ukai, S., Honma, R., Sakamoto, N., Yamamoto, Y., Pham, Q. T., Harada, K., et al. (2020). Molecular biological analysis of 5-FU-resistant gastric cancer organoids; KHDRBS3 contributes to the attainment of features of cancer stem cell. Oncogene, 39(50), 7265–7278. https://doi.org/10.1038/s41388-020-01492-9
Wu, Y., Sha, Y., Guo, X., Gao, L., Huang, J., & Liu, S.-B. (2025). Organoid models: applications and research advances in colorectal cancer. Frontiers in Oncology, 15, 1432506. https://doi.org/10.3389/fonc.2025.1432506
Xiang, T., Wang, J., & Li, H. (2024). Current applications of intestinal organoids: a review. Stem Cell Research & Therapy, 15, 155. https://doi.org/10.1186/s13287-024-03768-3
Yan, J., Monlong, J., Cougoule, C., Lacroix-Lamandé, S., & Wiedemann, A. (2024). Mapping the scientific output of organoids for animal and human modeling infectious diseases: a bibliometric assessment. Veterinary Research, 55, 81. https://doi.org/10.1186/s13567-024-01333-7
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Copyright (c) 2025 Jorge Angel Velasco Espinal, Sophia Celeste Sánchez Bertado, Edna Mariana Martínez López, Allison Fuentes Vega, Jesús Miguel Gama Velázquez, Emmanuel Navarro Clara, Frida Gabriela Cacique Vivanco (Autor/a)
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