Polyamines inhibit porin-mediated fluoroquinolone uptake in mycobacteria.

Polyamines decrease the permeability of the outer membrane of Escherichia coli to fluoroquinolones and β-lactams. In this study, we tested the effect of four polyamines (spermidine, spermine, cadaverine and putrescine) on fluoroquinolone uptake in Mycobacterium bovis BCG. Our results show that polya...

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Autores principales:	Jansy Passiflora Sarathy, Edmund Lee, Véronique Dartois
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2013
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/d2c7510d820747a2aec613fb7ea224d1
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spelling	oai:doaj.org-article:d2c7510d820747a2aec613fb7ea224d12021-11-18T07:43:10ZPolyamines inhibit porin-mediated fluoroquinolone uptake in mycobacteria.1932-620310.1371/journal.pone.0065806https://doaj.org/article/d2c7510d820747a2aec613fb7ea224d12013-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/23755283/?tool=EBIhttps://doaj.org/toc/1932-6203Polyamines decrease the permeability of the outer membrane of Escherichia coli to fluoroquinolones and β-lactams. In this study, we tested the effect of four polyamines (spermidine, spermine, cadaverine and putrescine) on fluoroquinolone uptake in Mycobacterium bovis BCG. Our results show that polyamines are also capable of reducing the permeability of the mycobacterial outer membrane to fluoroquinolones. Spermidine was most effective and demonstrated reversible dose- and pH-dependent inhibition of ciprofloxacin accumulation. The extent of this inhibition was demonstrated across the fluoroquinolone compound class to varying degrees. Furthermore, we have shown that the addition of spermidine increases the survival of M. bovis BCG after a 5-day exposure to ciprofloxacin by up to 25 times. The treatment of actively-replicating Mycobacterium tuberculosis with spermidine reduced ciprofloxacin accumulation by half while non-replicating nutrient-starved M. tuberculosis cultures lacked similar sensitivity to polyamines. Gene expression studies showed that several outer membrane proteins are significantly down-regulated during the shift to non-replication. Collectively, these characteristics of fluoroquinolone uptake in M. bovis BCG are consistent with facilitated transport by porin-like proteins and suggest that a reduction in intracellular uptake contributes to the phenotypic drug resistance demonstrated by M. tuberculosis in the non-replicating state.Jansy Passiflora SarathyEdmund LeeVéronique DartoisPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 8, Iss 6, p e65806 (2013)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Jansy Passiflora Sarathy Edmund Lee Véronique Dartois Polyamines inhibit porin-mediated fluoroquinolone uptake in mycobacteria.
description	Polyamines decrease the permeability of the outer membrane of Escherichia coli to fluoroquinolones and β-lactams. In this study, we tested the effect of four polyamines (spermidine, spermine, cadaverine and putrescine) on fluoroquinolone uptake in Mycobacterium bovis BCG. Our results show that polyamines are also capable of reducing the permeability of the mycobacterial outer membrane to fluoroquinolones. Spermidine was most effective and demonstrated reversible dose- and pH-dependent inhibition of ciprofloxacin accumulation. The extent of this inhibition was demonstrated across the fluoroquinolone compound class to varying degrees. Furthermore, we have shown that the addition of spermidine increases the survival of M. bovis BCG after a 5-day exposure to ciprofloxacin by up to 25 times. The treatment of actively-replicating Mycobacterium tuberculosis with spermidine reduced ciprofloxacin accumulation by half while non-replicating nutrient-starved M. tuberculosis cultures lacked similar sensitivity to polyamines. Gene expression studies showed that several outer membrane proteins are significantly down-regulated during the shift to non-replication. Collectively, these characteristics of fluoroquinolone uptake in M. bovis BCG are consistent with facilitated transport by porin-like proteins and suggest that a reduction in intracellular uptake contributes to the phenotypic drug resistance demonstrated by M. tuberculosis in the non-replicating state.
format	article
author	Jansy Passiflora Sarathy Edmund Lee Véronique Dartois
author_facet	Jansy Passiflora Sarathy Edmund Lee Véronique Dartois
author_sort	Jansy Passiflora Sarathy
title	Polyamines inhibit porin-mediated fluoroquinolone uptake in mycobacteria.
title_short	Polyamines inhibit porin-mediated fluoroquinolone uptake in mycobacteria.
title_full	Polyamines inhibit porin-mediated fluoroquinolone uptake in mycobacteria.
title_fullStr	Polyamines inhibit porin-mediated fluoroquinolone uptake in mycobacteria.
title_full_unstemmed	Polyamines inhibit porin-mediated fluoroquinolone uptake in mycobacteria.
title_sort	polyamines inhibit porin-mediated fluoroquinolone uptake in mycobacteria.
publisher	Public Library of Science (PLoS)
publishDate	2013
url	https://doaj.org/article/d2c7510d820747a2aec613fb7ea224d1
work_keys_str_mv	AT jansypassiflorasarathy polyaminesinhibitporinmediatedfluoroquinoloneuptakeinmycobacteria AT edmundlee polyaminesinhibitporinmediatedfluoroquinoloneuptakeinmycobacteria AT veroniquedartois polyaminesinhibitporinmediatedfluoroquinoloneuptakeinmycobacteria
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Polyamines inhibit porin-mediated fluoroquinolone uptake in mycobacteria.

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