2. Academic Validation
  3. Nitroxoline as an antimicrobial synergist reverses colistin resistance in multidrug-resistant Escherichia coli

Nitroxoline as an antimicrobial synergist reverses colistin resistance in multidrug-resistant Escherichia coli

  • iScience. 2025 Nov 10;28(12):114003. doi: 10.1016/j.isci.2025.114003.
Hao Wang 1,  Jie He 1,  Hao Li 1,  Chengming Li 1,  Muhammad Inam 2,  Jianfeng Wang 3,  Huifeng Dong 4,  Dingkuo Liu 4,  Fang Liu 4,  Jingrui Chen 1,  Yu Jia 5,  Yunhang Gao 1,  Lingcong Kong 1,  Hongxia Ma 1 5
Affiliations

Affiliations

  • 1 The Key Laboratory of New Veterinary Drug Research and Development of Jilin Province, College of Veterinary Medicine, Jilin Agricultural University, Changchun 130118, China.
  • 2 Department of Zoology, Shaheed Benazir Bhutto University Sheringal, Dir Upper 18050, Pakistan.
  • 3 State Key Laboratory for Diagnosis and Treatment of Severe Zoonotic Infectious Diseases, Key Laboratory for Zoonosis Research of the Ministry of Education, Institute of Zoonosis, College of Veterinary Medicine, Jilin University, Changchun 130062, China.
  • 4 Tianjin Key Laboratory of Biological Feed Additive Enterprise, S&E Burgeoning Biotechnology (Tianjin) Co., Ltd, Tianjin 300383, China.
  • 5 Engineering Research Center of Bioreactor and Pharmaceutical Development, Ministry of Education, Jilin Agricultural University, Changchun 130118, China.
PMID: 41377659 DOI: 10.1016/j.isci.2025.114003
Abstract

Colistin is a crucial drug for treating multidrug-resistant (MDR) Escherichia coli infections. The emergence and Bacterial transmission of the colistin-resistant gene mcr-1 have substantially diminished its therapeutic efficacy. The development of colistin enhancers represents an effective strategy to counteract this resistance. This study demonstrates that the FDA-approved drug nitroxoline (NTX) synergistically enhances the Antibacterial activity of colistin against mcr-1-positive MDR E. coli and effectively suppresses the development of colistin resistance. Functional assays and transcriptomic profiling demonstrate that NTX targets MCR-1, thereby potentiating the membrane-disruptive activity of colistin. Moreover, the combined administration of NTX and colistin perturbs Bacterial metabolic pathways, provokes oxidative damage, and accelerates Bacterial death. Furthermore, in both the Galleria mellonella and mouse peritonitis Infection models, NTX improved the therapeutic effect of colistin against E. coli infections. In conclusion, NTX is identified as a promising colistin Adjuvant for the treatment of colistin-resistant Bacterial infections.

Keywords

Biological sciences; Microbiology; Natural sciences; Pharmacology.

Figures
Products