Polymyxin Derivatives that Sensitize Gram-Negative Bacteria to Other Antibiotics

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http://hdl.handle.net/10138/300019

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Vaara , M 2019 , ' Polymyxin Derivatives that Sensitize Gram-Negative Bacteria to Other Antibiotics ' , Molecules , vol. 24 , no. 2 , 249 . https://doi.org/10.3390/molecules24020249

Title: Polymyxin Derivatives that Sensitize Gram-Negative Bacteria to Other Antibiotics
Author: Vaara, Martti
Contributor: University of Helsinki, Department of Bacteriology and Immunology
Date: 2019-01-02
Language: eng
Number of pages: 15
Belongs to series: Molecules
ISSN: 1420-3049
URI: http://hdl.handle.net/10138/300019
Abstract: Polymyxins (polymyxin B (PMB) and polymyxin E (colistin)) are cyclic lipodecapeptide antibiotics, highly basic due to five free amino groups, and rapidly bactericidal against Gram-negative bacteria, such as the majority of Enterobacteriaceae as well as Acinetobacter baumannii and Pseudomonas aeruginosa. Their clinical use was abandoned in the 1960s because of nephrotoxicity and because better-tolerated drugs belonging to other antibiotic classes were introduced. Now, due to the global dissemination of extremely-drug resistant Gram-negative bacterial strains, polymyxins have resurged as the last-line drugs against those strains. Novel derivatives that are less toxic and/or more effective at tolerable doses are currently under preclinical development and their properties have recently been described in several extensive reviews. Other derivatives lack any direct bactericidal activity but damage the outermost permeability barrier, the outer membrane, of the target bacteria and make it more permeable to many other antibiotics. This review describes the properties of three thus far best-characterized permeabilizer derivatives, i.e., the classic permeabilizer polymyxin B nonapeptide (PMBN), NAB7061, and SPR741/NAB741, a compound that recently successfully passed the clinical phase 1. Also, a few other permeabilizer compounds are brought up.
Subject: polymyxin B nonapeptide (PMBN)
NAB7061
SPR741
NAB741
Enterobacteriaceae
Acinetobacter baumannii
Pseudomonas aeruginosa
synergism
permeabilizers
clinical phase 1 study
3 POSITIVE CHARGES
OUTER-MEMBRANE
ANTIBACTERIAL ACTIVITY
ESCHERICHIA-COLI
HYDROPHOBIC ANTIBIOTICS
SYNERGISTIC ACTIVITY
DNA GYRASE
RESISTANT
AGENTS
LIPOPOLYSACCHARIDE
3111 Biomedicine
1182 Biochemistry, cell and molecular biology
116 Chemical sciences
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