Valnemulin restores colistin sensitivity against multidrug-resistant gram-negative pathogens

Bibliographic Details
Title: Valnemulin restores colistin sensitivity against multidrug-resistant gram-negative pathogens
Authors: Chen Xu, Yuan Zhang, Lingman Ma, Guangfen Zhang, Chunli Li, Chenjie Zhang, Yunbing Li, Xiangkun Zeng, Yuanyuan Li, Ning Dong
Source: Communications Biology, Vol 7, Iss 1, Pp 1-11 (2024)
Publisher Information: Nature Portfolio, 2024.
Publication Year: 2024
Collection: LCC:Biology (General)
Subject Terms: Biology (General), QH301-705.5
More Details: Abstract 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.
Document Type: article
File Description: electronic resource
Language: English
ISSN: 2399-3642
Relation: https://doaj.org/toc/2399-3642
DOI: 10.1038/s42003-024-06805-2
Access URL: https://doaj.org/article/6d6d5514022f4f8f8168a01ef5134c27
Accession Number: edsdoj.6d6d5514022f4f8f8168a01ef5134c27
Database: Directory of Open Access Journals
More Details
ISSN:23993642
DOI:10.1038/s42003-024-06805-2
Published in:Communications Biology
Language:English