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:	Lea Weber, Anna Hagemann, Jila Kaltenhäuser, Manuela Besser, Patrick Rockenfeller, Anja Ehrhardt, Ewa Stuermer, Hagen Sjard Bachmann
Formato:	article
Lenguaje:	EN
Publicado:	Frontiers Media S.A. 2021
Materias:	farnesyltransferase lonafarnib tipifarnib bacteria antibiotics Microbiology QR1-502
Acceso en línea:	https://doaj.org/article/a3e8589be9a54fd8be8389b29ac75ab9
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spelling	oai:doaj.org-article:a3e8589be9a54fd8be8389b29ac75ab92021-12-01T15:29:18ZBacteria Are New Targets for Inhibitors of Human Farnesyltransferase1664-302X10.3389/fmicb.2021.628283https://doaj.org/article/a3e8589be9a54fd8be8389b29ac75ab92021-11-01T00:00:00Zhttps://www.frontiersin.org/articles/10.3389/fmicb.2021.628283/fullhttps://doaj.org/toc/1664-302XFarnesyltransferase 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.Lea WeberAnna HagemannJila KaltenhäuserManuela BesserPatrick RockenfellerAnja EhrhardtEwa StuermerHagen Sjard BachmannFrontiers Media S.A.articlefarnesyltransferaselonafarnibtipifarnibbacteriaantibioticsMicrobiologyQR1-502ENFrontiers in Microbiology, Vol 12 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	farnesyltransferase lonafarnib tipifarnib bacteria antibiotics Microbiology QR1-502
spellingShingle	farnesyltransferase lonafarnib tipifarnib bacteria antibiotics Microbiology QR1-502 Lea Weber Anna Hagemann Jila Kaltenhäuser Manuela Besser Patrick Rockenfeller Anja Ehrhardt Ewa Stuermer Hagen Sjard Bachmann Bacteria Are New Targets for Inhibitors of Human Farnesyltransferase
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.
format	article
author	Lea Weber Anna Hagemann Jila Kaltenhäuser Manuela Besser Patrick Rockenfeller Anja Ehrhardt Ewa Stuermer Hagen Sjard Bachmann
author_facet	Lea Weber Anna Hagemann Jila Kaltenhäuser Manuela Besser Patrick Rockenfeller Anja Ehrhardt Ewa Stuermer Hagen Sjard Bachmann
author_sort	Lea Weber
title	Bacteria Are New Targets for Inhibitors of Human Farnesyltransferase
title_short	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_sort	bacteria are new targets for inhibitors of human farnesyltransferase
publisher	Frontiers Media S.A.
publishDate	2021
url	https://doaj.org/article/a3e8589be9a54fd8be8389b29ac75ab9
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Bacteria Are New Targets for Inhibitors of Human Farnesyltransferase

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