Mechanisms of a Mycobacterium tuberculosis Active Peptide

Research output: Contribution to journal › Journal article › Research › peer-review

Standard

Mechanisms of a Mycobacterium tuberculosis Active Peptide. / Rao, Komal Umashankar; Li, Ping; Welinder, Charlotte; Tenland, Erik; Gourdon, Pontus; Sturegård, Erik; Ho, James C S; Godaly, Gabriela.

In: Pharmaceutics, Vol. 15, No. 2, 540, 2023.

Research output: Contribution to journal › Journal article › Research › peer-review

Harvard

Rao, KU, Li, P, Welinder, C, Tenland, E, Gourdon, P, Sturegård, E, Ho, JCS & Godaly, G 2023, 'Mechanisms of a Mycobacterium tuberculosis Active Peptide', Pharmaceutics, vol. 15, no. 2, 540. https://doi.org/10.3390/pharmaceutics15020540

APA

Rao, K. U., Li, P., Welinder, C., Tenland, E., Gourdon, P., Sturegård, E., Ho, J. C. S., & Godaly, G. (2023). Mechanisms of a Mycobacterium tuberculosis Active Peptide. Pharmaceutics, 15(2), [540]. https://doi.org/10.3390/pharmaceutics15020540

Vancouver

Rao KU, Li P, Welinder C, Tenland E, Gourdon P, Sturegård E et al. Mechanisms of a Mycobacterium tuberculosis Active Peptide. Pharmaceutics. 2023;15(2). 540. https://doi.org/10.3390/pharmaceutics15020540

Author

Rao, Komal Umashankar ; Li, Ping ; Welinder, Charlotte ; Tenland, Erik ; Gourdon, Pontus ; Sturegård, Erik ; Ho, James C S ; Godaly, Gabriela. / Mechanisms of a Mycobacterium tuberculosis Active Peptide. In: Pharmaceutics. 2023 ; Vol. 15, No. 2.

Bibtex

@article{344d452560734468b5a0bc8efdca7311,
title = "Mechanisms of a Mycobacterium tuberculosis Active Peptide",
abstract = "Multidrug-resistant tuberculosis (MDR) continues to pose a threat to public health. Previously, we identified a cationic host defense peptide with activity against Mycobacterium tuberculosis in vivo and with a bactericidal effect against MDR M. tuberculosis at therapeutic concentrations. To understand the mechanisms of this peptide, we investigated its interactions with live M. tuberculosis and liposomes as a model. Peptide interactions with M. tuberculosis 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 M. tuberculosis, 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.",
author = "Rao, {Komal Umashankar} and Ping Li and Charlotte Welinder and Erik Tenland and Pontus Gourdon and Erik Stureg{\aa}rd and Ho, {James C S} and Gabriela Godaly",
year = "2023",
doi = "10.3390/pharmaceutics15020540",
language = "English",
volume = "15",
journal = "Pharmaceutics",
issn = "1999-4923",
publisher = "MDPI AG",
number = "2",

}

RIS

TY - JOUR

T1 - Mechanisms of a Mycobacterium tuberculosis Active Peptide

AU - Rao, Komal Umashankar

AU - Li, Ping

AU - Welinder, Charlotte

AU - Tenland, Erik

AU - Gourdon, Pontus

AU - Sturegård, Erik

AU - Ho, James C S

AU - Godaly, Gabriela

PY - 2023

Y1 - 2023

N2 - Multidrug-resistant tuberculosis (MDR) continues to pose a threat to public health. Previously, we identified a cationic host defense peptide with activity against Mycobacterium tuberculosis in vivo and with a bactericidal effect against MDR M. tuberculosis at therapeutic concentrations. To understand the mechanisms of this peptide, we investigated its interactions with live M. tuberculosis and liposomes as a model. Peptide interactions with M. tuberculosis 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 M. tuberculosis, 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.

AB - Multidrug-resistant tuberculosis (MDR) continues to pose a threat to public health. Previously, we identified a cationic host defense peptide with activity against Mycobacterium tuberculosis in vivo and with a bactericidal effect against MDR M. tuberculosis at therapeutic concentrations. To understand the mechanisms of this peptide, we investigated its interactions with live M. tuberculosis and liposomes as a model. Peptide interactions with M. tuberculosis 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 M. tuberculosis, 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.

U2 - 10.3390/pharmaceutics15020540

DO - 10.3390/pharmaceutics15020540

M3 - Journal article

C2 - 36839864

VL - 15

JO - Pharmaceutics

JF - Pharmaceutics

SN - 1999-4923

IS - 2

M1 - 540

ER -

ID: 338428535