已发表论文

肠道定植的耐碳青霉烯类肠杆菌科细菌释放的外膜囊泡可降解抗生素并促进细菌存活

 

Authors Li P, Lin Y, Sun X, Huang J, Huang D, Xu Y

Received 14 August 2025

Accepted for publication 29 November 2025

Published 10 December 2025 Volume 2025:18 Pages 6509—6519

DOI https://doi.org/10.2147/IDR.S557028

Checked for plagiarism Yes

Review by Single anonymous peer review

Peer reviewer comments 3

Editor who approved publication: Dr Hemant Joshi

Peifen Li,* Yingying Lin,* Xihuan Sun,* Jiaming Huang, Donghong Huang, Yujin Xu

Clinical Microbiology Laboratory, The Second Affiliated Hospital of Fujian Medical University, Quanzhou, Fujian, People’s Republic of China

*These authors contributed equally to this work

Correspondence: Yujin Xu, Clinical Microbiology Laboratory, The Second Affiliated Hospital of Fujian Medical University, Donghai Street No. 950, Quanzhou, Fujian, 362000, People’s Republic of China, Tel +86-18158090986, Fax +0595-22770258, Email xyj815@fjmu.edu.cn

Purpose: Gut colonization of carbapenem-resistant Enterobacterales (CRE) poses a significant risk for systemic infections, but the mechanisms driving resistance dissemination are poorly understood. This study aimed to investigate whether outer membrane vesicles (OMVs) secreted by gut-colonized CRE can enter the human circulatory system and mediate extracellular antibiotic resistance through functional carbapenemases and resistance genes.
Patients and Methods: We conducted comparative proteomic analyses of OMVs isolated from parental CRE strains and patient plasma samples. Antibiotic degradation assays were performed to evaluate OMV-mediated hydrolysis of imipenem and meropenem. In vitro experiments assessed the protective effects of OMVs on carbapenem-susceptible Escherichia coli and Pseudomonas aeruginosa. Additionally, a Galleria mellonella infection model was used to examine OMV-mediated bacterial survival under carbapenem pressure.
Results: Plasma-derived OMVs exhibited proteomic profiles similar to bacterial OMVs, including carbapenemase components, and demonstrated comparable antibiotic-degrading activity. These OMVs hydrolyzed 60– 75% of imipenem and meropenem within 24 hours, protecting susceptible bacteria from growth inhibition in vitro. Although no horizontal gene transfer was observed, OMVs enhanced Klebsiella pneumoniae survival under carbapenem pressure in the G. mellonella model, increasing larval survival rates by 25%.
Conclusion: Our findings reveal a novel OMV-mediated extracellular resistance mechanism that operates independently of genetic transfer, promoting bacterial persistence in the bloodstream. This study provides key insights into the role of OMVs in clinical treatment failure and identifies potential therapeutic targets to combat antibiotic resistance dissemination.

Keywords: outer membrane vesicles, carbapenem-resistant enterobacterales, CRE, carbapenemase, antibiotic degradation, intestinal colonization