白色念珠菌–细菌混合感染脓毒症患者中外泌体对细菌耐药机制研究
Study on the Role of Exosomes in Mechanisms of Bacterial Antibiotic Resistance in Patients with Sepsis Caused by Candida albicans-Bacterial Co-Infection
DOI: 10.12677/acm.2025.1572021, PDF,    科研立项经费支持
作者: 孟繁晓, 徐喜媛*, 王宏燕:包头医学院内蒙古包钢医院呼吸与危重症医学科,内蒙古 包头
关键词: 白色念珠菌外泌体大肠杆菌耐药性细菌–真菌共感染脓毒症Candida albicans Exosomes Escherichia coli Antibiotic Resistance Bacterial-Fungal Co-Infection Sepsis
摘要: 目的:探讨白色念珠菌外泌体在细菌–真菌混合感染脓毒症患者中对细菌耐药性的影响及其机制。方法:收集6例脓毒症患者肺泡灌洗液(3例单纯细菌感染,3例混合感染),通过宏基因组测序(mNGS)筛选样本;采用超速离心法提取外泌体,透射电镜和纳米流式鉴定其特性;通过蛋白质组学分析差异蛋白表达。结果:混合感染组中,白色念珠菌外泌体蛋白TSA1_CANAL (过氧化物还原酶)和ADH1_CANAX (醇脱氢酶)表达显著升高。结论:白色念珠菌外泌体通过上调氧化应激相关蛋白表达,特异性增强大肠杆菌对β-内酰胺类抗生素的耐药性,提示真菌–细菌互作在脓毒症治疗中具有重要临床意义,为优化抗感染策略提供了新靶点。
Abstract: Objective: To explore the effects of Candida albicans exosomes on bacterial drug resistance and its mechanism in patients with bacterial-fungal mixed infection sepsis. Methods: Alveolar lavage fluid (3 simple bacterial infections and 3 mixed infections) in sepsis patients were collected, and samples were screened by metagenomic sequencing (mNGS). Exosomes were extracted by ultracentrifugation, and their characteristics were identified by transmission electron microscopy and nanoflow. Differential protein expression was analyzed by proteomics. Results: In the mixed infection group, the expression of Candida albicans exosome proteins TSA1_CANAL (peroxide reductase) and ADH1_CANAX (alcohol dehydrogenase) was significantly increased. Conclusion: The Candida albicans exosomes specifically enhance the resistance of E. coli to β-lactam antibiotics by upregulating the expression of oxidative stress-related proteins, suggesting that fungal-bacterial interactions are of great clinical significance in the treatment of sepsis and provide a new target for optimizing anti-infection strategies.
文章引用:孟繁晓, 徐喜媛, 王宏燕. 白色念珠菌–细菌混合感染脓毒症患者中外泌体对细菌耐药机制研究[J]. 临床医学进展, 2025, 15(7): 537-547. https://doi.org/10.12677/acm.2025.1572021

参考文献

[1] Rhodes, A., Evans, L.E., Alhazzani, W., Levy, M.M., Antonelli, M., Ferrer, R., et al. (2017) Surviving Sepsis Campaign: International Guidelines for Management of Sepsis and Septic Shock: 2016. Intensive Care Medicine, 43, 304-377. [Google Scholar] [CrossRef] [PubMed]
[2] Kelly, B.T., Pennington, K.M. and Limper, A.H. (2020) Advances in the Diagnosis of Fungal Pneumonias. Expert Review of Respiratory Medicine, 14, 703-714. [Google Scholar] [CrossRef] [PubMed]
[3] Sionov, R.V. and Steinberg, D. (2022) Targeting the Holy Triangle of Quorum Sensing, Biofilm Formation, and Antibiotic Resistance in Pathogenic Bacteria. Microorganisms, 10, Article 1239. [Google Scholar] [CrossRef] [PubMed]
[4] 李昕, 曾洁, 王岱, 等. 细菌耐药耐受性机制的最新研究进展[J]. 中国抗生素杂志, 2020, 45(2): 113-121.
[5] Jiang, B., Lai, Y., Xiao, W., Zhong, T., Liu, F., Gong, J., et al. (2024) Microbial Extracellular Vesicles Contribute to Antimicrobial Resistance. PLOS Pathogens, 20, e1012143. [Google Scholar] [CrossRef] [PubMed]
[6] Semenec, L., Cain, A.K., Dawson, C.J., Liu, Q., Dinh, H., Lott, H., et al. (2023) Cross-Protection and Cross-Feeding between Klebsiella Pneumoniae and Acinetobacter Baumannii Promotes Their Co-Existence. Nature Communications, 14, Article No. 702. [Google Scholar] [CrossRef] [PubMed]
[7] Dolan, S.K., Duong, A.T. and Whiteley, M. (2024) Convergent Evolution in Toxin Detection and Resistance Provides Evidence for Conserved Bacterial-Fungal Interactions. Proceedings of the National Academy of Sciences, 121, e2304382121. [Google Scholar] [CrossRef] [PubMed]
[8] Allison, D.L., Willems, H.M.E., Jayatilake, J.A.M.S., Bruno, V.M., Peters, B.M. and Shirtliff, M.E. (2016) Candida-Bacteria Interactions: Their Impact on Human Disease. Microbiology Spectrum, 4, 1-26. [Google Scholar] [CrossRef] [PubMed]
[9] Kong, E.F., Tsui, C., Kucharíková, S., Andes, D., Van Dijck, P. and Jabra-Rizk, M.A. (2016) Commensal Protection of Staphylococcus aureus against Antimicrobials by Candida albicans Biofilm Matrix. mBio, 7, 1-12. [Google Scholar] [CrossRef] [PubMed]
[10] Moretti, M., Grunau, A., Minerdi, D., Gehrig, P., Roschitzki, B., Eberl, L., et al. (2010) A Proteomics Approach to Study Synergistic and Antagonistic Interactions of the Fungal-Bacterial Consortium Fusarium oxysporum Wild-Type MSA 35. Proteomics, 10, 3292-3320. [Google Scholar] [CrossRef] [PubMed]
[11] Seymour, C.W., Liu, V.X., Iwashyna, T.J., Brunkhorst, F.M., Rea, T.D., Scherag, A., et al. (2016) Assessment of Clinical Criteria for Sepsis. Journal of the American Medical Association, 315, Article 762. [Google Scholar] [CrossRef] [PubMed]
[12] 君安医学细胞平台专家委员会. 支气管肺泡灌洗液细胞形态学检验中国专家共识(2023) [J]. 现代检验医学杂志, 2023, 38(3): 11-16+23.
[13] UniProt Consortium (2024) UniProt: The Universal Protein Knowledgebase in 2025. Nucleic Acids Research, 53, D609-D617.
[14] Urban, C., Xiong, X., Sohn, K., Schröppel, K., Brunner, H. and Rupp, S. (2005) The Moonlighting Protein Tsa1p Is Implicated in Oxidative Stress Response and in Cell Wall Biogenesis in Candida albicans. Molecular Microbiology, 57, 1318-1341. [Google Scholar] [CrossRef] [PubMed]
[15] Bassetti, M., Garnacho-Montero, J., Calandra, T., Kullberg, B., Dimopoulos, G., Azoulay, E., et al. (2017) Intensive Care Medicine Research Agenda on Invasive Fungal Infection in Critically Ill Patients. Intensive Care Medicine, 43, 1225-1238. [Google Scholar] [CrossRef] [PubMed]
[16] Dickson, R.P., Schultz, M.J., van der Poll, T., Schouten, L.R., Falkowski, N.R., Luth, J.E., et al. (2020) Lung Microbiota Predict Clinical Outcomes in Critically Ill Patients. American Journal of Respiratory and Critical Care Medicine, 201, 555-563. [Google Scholar] [CrossRef] [PubMed]
[17] Church, D.L., Cerutti, L., Gürtler, A., Griener, T., Zelazny, A. and Emler, S. (2020) Performance and Application of 16S rRNA Gene Cycle Sequencing for Routine Identification of Bacteria in the Clinical Microbiology Laboratory. Clinical Microbiology Reviews, 33, Article 73. [Google Scholar] [CrossRef] [PubMed]
[18] Sun, L., Zhang, S., Yang, Z., Yang, F., Wang, Z., Li, H., et al. (2022) Clinical Application and Influencing Factor Analysis of Metagenomic Next-Generation Sequencing (mNGS) in ICU Patients with Sepsis. Frontiers in Cellular and Infection Microbiology, 12, Article 905132. [Google Scholar] [CrossRef] [PubMed]
[19] (2005) Guidelines for the Management of Adults with Hospital-Acquired, Ventilator-Associated, and Healthcare-Associated Pneumonia. American Journal of Respiratory and Critical Care Medicine, 171, 388-416. [Google Scholar] [CrossRef
[20] Tsatsaronis, J.A., Franch-Arroyo, S., Resch, U. and Charpentier, E. (2018) Extracellular Vesicle RNA: A Universal Mediator of Microbial Communication? Trends in Microbiology, 26, 401-410. [Google Scholar] [CrossRef] [PubMed]
[21] da Silva Dantas, A., Patterson, M.J., Smith, D.A., MacCallum, D.M., Erwig, L.P., Morgan, B.A., et al. (2010) Thioredoxin Regulates Multiple Hydrogen Peroxide-Induced Signaling Pathways in Candida albicans. Molecular and Cellular Biology, 30, 4550-4563. [Google Scholar] [CrossRef] [PubMed]
[22] Wang, Z., Zhang, Q., Zhang, H. and Lu, Y. (2024) Roles of Alcohol Dehydrogenase 1 in the Biological Activities of Candida albicans. Critical Reviews in Microbiology, 51, 484-498. [Google Scholar] [CrossRef] [PubMed]
[23] Jiang, Z., Kan, J., Wang, D., Lv, Y., Kong, C., Wu, L., et al. (2025) Inhibition of GRK2 Reduced Doxorubicin-Induced Oxidative Stress and Apoptosis through Upregulating Adh1. Toxicology and Applied Pharmacology, 497, Article 117261. [Google Scholar] [CrossRef] [PubMed]
[24] Ye, D., Sun, J., Jiang, R., Chang, J., Liu, Y., Wu, X., et al. (2024) β-Lactam Antibiotics Induce Metabolic Perturbations Linked to ROS Generation Leads to Bacterial Impairment. Frontiers in Microbiology, 15, Article 1514825. [Google Scholar] [CrossRef] [PubMed]
[25] Liu, M., Wang, M., Huang, M., Gao, Q., Zhu, D., Wang, M., et al. (2024) Iron Efflux by IetA Enhances β-Lactam Aztreonam Resistance and Is Linked to Oxidative Stress through Cellular Respiration in Riemerella anatipestifer. Journal of Antimicrobial Chemotherapy, 79, 1385-1396. [Google Scholar] [CrossRef] [PubMed]