Mechanisms of a Mycobacterium tuberculosis Active Peptide

Multidrug-resistant tuberculosis (MDR) continues to pose a threat to public health. Previously, we identified a cationic host defense peptide with activity against in vivo and with a bactericidal effect against MDR at therapeutic concentrations. To understand the mechanisms of this peptide, we inves...

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Published inPharmaceutics Vol. 15; no. 2; p. 540
Main Authors Rao, Komal Umashankar, Li, Ping, Welinder, Charlotte, Tenland, Erik, Gourdon, Pontus, Sturegård, Erik, Ho, James C S, Godaly, Gabriela
Format Journal Article
LanguageEnglish
Published Switzerland MDPI AG 06.02.2023
MDPI
Subjects
Antibiotics
Antimicrobial agents
antimicrobial peptides
Bacteria
Biochemistry and Molecular Biology
Biokemi och molekylärbiologi
Biologi
Biological Sciences
Chromatography
Drug resistance
Glycerol
Infections
Kinetics
Laboratories
Lipids
mechanisms of action
Mycobacterium tuberculosis
Natural Sciences
Naturvetenskap
Pathogens
Peptides
Scanning electron microscopy
Transmission electron microscopy
treatment
Tuberculosis
United Kingdom > UK
United States > US
Sweden
treatment
Mycobacterium tuberculosis
antimicrobial peptides
mechanisms of action
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Summary:Multidrug-resistant tuberculosis (MDR) continues to pose a threat to public health. Previously, we identified a cationic host defense peptide with activity against in vivo and with a bactericidal effect against MDR at therapeutic concentrations. To understand the mechanisms of this peptide, we investigated its interactions with live and liposomes as a model. Peptide interactions with inner membranes induced tube-shaped membranous structures and massive vesicle formation, thus leading to bubbling cell death and ghost cell formation. Liposomal studies revealed that peptide insertion into inner membranes induced changes in the peptides' secondary structure and that the membranes were pulled such that they aggregated without permeabilization, suggesting that the peptide has a strong inner membrane affinity. Finally, the peptide targeted essential proteins in , such as 60 kDa chaperonins and elongation factor Tu, that are involved in mycolic acid synthesis and protein folding, which had an impact on bacterial proliferation. The observed multifaceted targeting provides additional support for the therapeutic potential of this peptide.
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ISSN:1999-4923
1999-4923
DOI:10.3390/pharmaceutics15020540