Acquisition of Resistance to PEGylated Branched Polyethylenimine Increases Pseudomonas Aeruginosa Susceptibility to Aminoglycosides.
ChemMedChem
; : e202300689, 2024 May 28.
Article
em En
| MEDLINE
| ID: mdl-38806411
ABSTRACT
PEGylated branched polyethylenimine (PEG-BPEI) has antibacterial and antibiofilm properties. Exposure to PEG-BPEI through serial passage leads to resistant P. aeruginosa strains. The minimum inhibitory concentration (MIC) of 600â
Da BPEI and PEGylated 600â
Da BPEI (PEG-BPEI) in the wild-type PAO1 strain is 16â
µg/ml while, after 15 serial passages, the MIC increased to 1024â
µg/mL. An additional 15 rounds of serial passage in the absence of BPEI or PEG-BPEI did not change the 1024â
µg/mL MIC. Gentamicin, Neomycin, and Tobramycin, cationic antibiotics that inhibit protein synthesis, have a 16-32 fold reduction of MIC values in PEG350-BPEI resistant strains, suggesting increased permeation. The influx of these antibiotics occurs using a self-mediated uptake mechanism, suggesting changes to the outer membrane Data show that resistance causes changes in genes related to outer membrane lipopolysaccharide (LPS) assembly. Mutations were noted in the gene coding for the polymerase Wzy that participates in the assembly of the O-antigen region. Other mutations were noted with wbpE and wbpI of the Wbp pathway responsible for the enzymatic synthesis of ManNAc(3NAc)A in the LPS of P. aeruginosa. These changes suggest that an altered gene product could lead to PEG-BPEI resistance. Nevertheless, the increased susceptibility to aminoglycosides could prevent the emergence of PEG-BPEI resistant bacterial populations.
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01-internacional
Base de dados:
MEDLINE
Idioma:
En
Revista:
ChemMedChem
Ano de publicação:
2024
Tipo de documento:
Article