Valnemulin restores colistin sensitivity against multidrug-resistant gram-negative pathogens
Colistin is one of the last-resort antibiotics in treating infections caused by multidrug-resistant (MDR) pathogens. Unfortunately, the emergence of colistin-resistant gram-negative strains limit its clinical application. Here, we identify an FDA-approved drug, valnemulin (Val), exhibit a synergistic effect with colistin in eradicating both colistin-resistant and colistin-susceptible gram-negative pathogens both in vitro and in the mouse infection model. Furthermore, Val acts synergistically with colistin in eliminating intracellular bacteria in vitro. Functional studies and transcriptional analysis confirm that the combinational use of Val and colistin could cause membrane permeabilization, proton motive force dissipation, reduction in intracellular ATP level, and suppression in bacterial motility, which result in bacterial membrane disruption and finally cell death. Our findings reveal the potential of Val as a colistin adjuvant to combat MDR bacterial pathogens and treat recalcitrant infections.
Authors
- Yunbing Li
- Chenjie Zhang (ORCID: https://orcid.org/0000-0001-8755-4070)
- Yuanyuan Li (ORCID: https://orcid.org/0000-0003-0931-6928)
- Guang-Fen Zhang (ORCID: https://orcid.org/0000-0002-3934-8368)
- Ning Dong (ORCID: https://orcid.org/0000-0001-6515-4201)
- Yuan Zhang (ORCID: https://orcid.org/0000-0002-4174-0641)
- Chunli Li (ORCID: https://orcid.org/0000-0002-1053-7210)
- Chen Xu (ORCID: https://orcid.org/0000-0001-6980-0581)
- Lingman Ma (ORCID: https://orcid.org/0000-0002-4114-6079)
- Xiangkun Zeng
Institutions
- Jiangsu University (CN)
- China Pharmaceutical University (CN)
- Soochow University (CN)
- Second Affiliated Hospital of Zhejiang University (CN)
- Chongqing Medical University (CN)
Publication Details
- Journal
- Communications Biology
- Published
- 2024-09-12
- DOI
- https://doi.org/10.1038/s42003-024-06805-2
- Citations
- 10
- Primary Topic
- Antibiotic Resistance in Bacteria
- Type
- article
- Field-Weighted Citation Impact
- 1.70
Funders
- National Natural Science Foundation of China
- Jiangsu University
- China Postdoctoral Science Foundation
- Government of Jiangsu Province
- Natural Science Foundation of Jiangsu Province
- Priority Academic Program Development of Jiangsu Higher Education Institutions
- Senior Talent Foundation of Jiangsu University
- Postdoctoral Research Foundation of China