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Bacteria Are New Targets for Inhibitors of Human Farnesyltransferase

Farnesyltransferase inhibitors (FTIs) are focus for the treatment of several diseases, particularly in the field of cancer therapy. Their potential, however, goes even further, as a number of studies have evaluated FTIs for the treatment of infectious diseases such as malaria, African sleeping sickn...

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Autores principales: Weber, Lea, Hagemann, Anna, Kaltenhäuser, Jila, Besser, Manuela, Rockenfeller, Patrick, Ehrhardt, Anja, Stuermer, Ewa, Bachmann, Hagen Sjard
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8669142/
https://www.ncbi.nlm.nih.gov/pubmed/34917041
http://dx.doi.org/10.3389/fmicb.2021.628283
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author Weber, Lea
Hagemann, Anna
Kaltenhäuser, Jila
Besser, Manuela
Rockenfeller, Patrick
Ehrhardt, Anja
Stuermer, Ewa
Bachmann, Hagen Sjard
author_facet Weber, Lea
Hagemann, Anna
Kaltenhäuser, Jila
Besser, Manuela
Rockenfeller, Patrick
Ehrhardt, Anja
Stuermer, Ewa
Bachmann, Hagen Sjard
author_sort Weber, Lea
collection PubMed
description Farnesyltransferase inhibitors (FTIs) are focus for the treatment of several diseases, particularly in the field of cancer therapy. Their potential, however, goes even further, as a number of studies have evaluated FTIs for the treatment of infectious diseases such as malaria, African sleeping sickness, leishmaniosis, and hepatitis D virus infection. Little is known about protein prenylation mechanisms in human pathogens. However, disruption of IspA, a gene encoding the geranyltranstransferase of Staphylococcus aureus (S. aureus) leads to reprogramming of cellular behavior as well as impaired growth and decreased resistance to cell wall-targeting antibiotics. We used an agar well diffusion assay and a time kill assay and determined the minimum inhibitory concentrations of the FTIs lonafarnib and tipifarnib. Additionally, we conducted cell viability assays. We aimed to characterize the effect of these FTIs on S. aureus, methicillin-resistant Staphylococcus aureus (MRSA), Staphylococcus epidermidis (S. epidermidis), Escherichia coli (E. coli), Enterococcus faecium (E. faecium), Klebsiella pneumoniae (K. pneumoniae), Pseudomonas aeruginosa (P. aeruginosa), and Streptococcus pneumoniae (S. pneumoniae). Both the FTIs lonafarnib and tipifarnib were capable of inhibiting the growth of the Gram-positive bacteria S. aureus, MRSA, S. epidermidis, and S. pneumoniae, whereas no effect was observed on Gram-negative bacteria. The analysis of the impact of lonafarnib and tipifarnib on common human pathogens might lead to novel insights into their defense mechanisms and therefore provide new therapeutic targets for antibiotic-resistant bacterial infections.
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spelling pubmed-86691422021-12-15 Bacteria Are New Targets for Inhibitors of Human Farnesyltransferase Weber, Lea Hagemann, Anna Kaltenhäuser, Jila Besser, Manuela Rockenfeller, Patrick Ehrhardt, Anja Stuermer, Ewa Bachmann, Hagen Sjard Front Microbiol Microbiology Farnesyltransferase inhibitors (FTIs) are focus for the treatment of several diseases, particularly in the field of cancer therapy. Their potential, however, goes even further, as a number of studies have evaluated FTIs for the treatment of infectious diseases such as malaria, African sleeping sickness, leishmaniosis, and hepatitis D virus infection. Little is known about protein prenylation mechanisms in human pathogens. However, disruption of IspA, a gene encoding the geranyltranstransferase of Staphylococcus aureus (S. aureus) leads to reprogramming of cellular behavior as well as impaired growth and decreased resistance to cell wall-targeting antibiotics. We used an agar well diffusion assay and a time kill assay and determined the minimum inhibitory concentrations of the FTIs lonafarnib and tipifarnib. Additionally, we conducted cell viability assays. We aimed to characterize the effect of these FTIs on S. aureus, methicillin-resistant Staphylococcus aureus (MRSA), Staphylococcus epidermidis (S. epidermidis), Escherichia coli (E. coli), Enterococcus faecium (E. faecium), Klebsiella pneumoniae (K. pneumoniae), Pseudomonas aeruginosa (P. aeruginosa), and Streptococcus pneumoniae (S. pneumoniae). Both the FTIs lonafarnib and tipifarnib were capable of inhibiting the growth of the Gram-positive bacteria S. aureus, MRSA, S. epidermidis, and S. pneumoniae, whereas no effect was observed on Gram-negative bacteria. The analysis of the impact of lonafarnib and tipifarnib on common human pathogens might lead to novel insights into their defense mechanisms and therefore provide new therapeutic targets for antibiotic-resistant bacterial infections. Frontiers Media S.A. 2021-11-30 /pmc/articles/PMC8669142/ /pubmed/34917041 http://dx.doi.org/10.3389/fmicb.2021.628283 Text en Copyright © 2021 Weber, Hagemann, Kaltenhäuser, Besser, Rockenfeller, Ehrhardt, Stuermer and Bachmann. https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Microbiology
Weber, Lea
Hagemann, Anna
Kaltenhäuser, Jila
Besser, Manuela
Rockenfeller, Patrick
Ehrhardt, Anja
Stuermer, Ewa
Bachmann, Hagen Sjard
Bacteria Are New Targets for Inhibitors of Human Farnesyltransferase
title Bacteria Are New Targets for Inhibitors of Human Farnesyltransferase
title_full Bacteria Are New Targets for Inhibitors of Human Farnesyltransferase
title_fullStr Bacteria Are New Targets for Inhibitors of Human Farnesyltransferase
title_full_unstemmed Bacteria Are New Targets for Inhibitors of Human Farnesyltransferase
title_short Bacteria Are New Targets for Inhibitors of Human Farnesyltransferase
title_sort bacteria are new targets for inhibitors of human farnesyltransferase
topic Microbiology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8669142/
https://www.ncbi.nlm.nih.gov/pubmed/34917041
http://dx.doi.org/10.3389/fmicb.2021.628283
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