Second-Generation Tryptamine Derivatives Potently Sensitize Colistin Resistant Bacteria to Colistin.
Basic Information
ID: ALA4304756
Journal: ACS Med Chem Lett
Title: Second-Generation Tryptamine Derivatives Potently Sensitize Colistin Resistant Bacteria to Colistin.
Authors: Minrovic BM, Hubble VB, Barker WT, Jania LA, Melander RJ, Koller BH, Melander C.
Abstract: Antibiotic resistance has significantly increased since the beginning of the 21st century. Currently, the polymyxin colistin is typically viewed as the antibiotic of last resort for the treatment of multidrug resistant Gram-negative bacterial infections. However, increased colistin usage has resulted in colistin-resistant bacterial isolates becoming more common. The recent dissemination of plasmid-borne colistin resistance genes (mcr 1-8) into the human pathogen pool is further threatening to render colistin therapy ineffective. New methods to combat antibiotic resistant pathogens are needed. Herein, the utilization of a colistin-adjuvant combination that is effective against colistin-resistant bacteria is described. At 5 μM, the lead adjuvant, which is nontoxic to the bacteria alone, increases colistin efficacy 32-fold against bacteria containing the mcr-1 gene and effects a 1024-fold increase in colistin efficacy against bacteria harboring chromosomally encoded colistin resistance determinants; these combinations lower the colistin minimum inhibitory concentration (MIC) to or below clinical breakpoint levels (≤2 μg/mL).
CiteXplore: 31098007
DOI: 10.1021/acsmedchemlett.9b00135
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