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Antibacterial and Antivirulence Activity of Glucocorticoid PYED-1 against Stenotrophomonas maltophilia

Stenotrophomonas maltophilia, an environmental Gram-negative bacterium, is an emerging nosocomial opportunistic pathogen that causes life-threatening infections in immunocompromised patients and chronic pulmonary infections in cystic fibrosis patients. Due to increasing resistance to multiple classe...

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Autores principales: Esposito, Anna, Vollaro, Adriana, Esposito, Eliana Pia, D’Alonzo, Daniele, Guaragna, Annalisa, Zarrilli, Raffaele, De Gregorio, Eliana
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7148523/
https://www.ncbi.nlm.nih.gov/pubmed/32131413
http://dx.doi.org/10.3390/antibiotics9030105
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author Esposito, Anna
Vollaro, Adriana
Esposito, Eliana Pia
D’Alonzo, Daniele
Guaragna, Annalisa
Zarrilli, Raffaele
De Gregorio, Eliana
author_facet Esposito, Anna
Vollaro, Adriana
Esposito, Eliana Pia
D’Alonzo, Daniele
Guaragna, Annalisa
Zarrilli, Raffaele
De Gregorio, Eliana
author_sort Esposito, Anna
collection PubMed
description Stenotrophomonas maltophilia, an environmental Gram-negative bacterium, is an emerging nosocomial opportunistic pathogen that causes life-threatening infections in immunocompromised patients and chronic pulmonary infections in cystic fibrosis patients. Due to increasing resistance to multiple classes of antibiotics, S. maltophilia infections are difficult to treat successfully. This makes the search for new antimicrobial strategies mandatory. In this study, the antibacterial activity of the heterocyclic corticosteroid deflazacort and several of its synthetic precursors was tested against S. maltophilia. All compounds were not active against standard strain S. maltophilia K279a. The compound PYED-1 (pregnadiene-11-hydroxy-16α,17α-epoxy-3,20-dione-1) showed a weak effect against some S. maltophilia clinical isolates, but exhibited a synergistic effect with aminoglycosides. PYED-1 at sub-inhibitory concentrations decreased S. maltophilia biofilm formation. Quantitative real-time polymerase chain reaction (RT-qPCR) analysis demonstrated that the expression of biofilm- and virulence- associated genes (StmPr1, StmPr3, sphB, smeZ, bfmA, fsnR) was significantly suppressed after PYED-1 treatment. Interestingly, PYED-1 also repressed the expression of the genes aph (3′)-IIc, aac (6′)-Iz, and smeZ, involved in the resistance to aminoglycosides.
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spelling pubmed-71485232020-04-20 Antibacterial and Antivirulence Activity of Glucocorticoid PYED-1 against Stenotrophomonas maltophilia Esposito, Anna Vollaro, Adriana Esposito, Eliana Pia D’Alonzo, Daniele Guaragna, Annalisa Zarrilli, Raffaele De Gregorio, Eliana Antibiotics (Basel) Article Stenotrophomonas maltophilia, an environmental Gram-negative bacterium, is an emerging nosocomial opportunistic pathogen that causes life-threatening infections in immunocompromised patients and chronic pulmonary infections in cystic fibrosis patients. Due to increasing resistance to multiple classes of antibiotics, S. maltophilia infections are difficult to treat successfully. This makes the search for new antimicrobial strategies mandatory. In this study, the antibacterial activity of the heterocyclic corticosteroid deflazacort and several of its synthetic precursors was tested against S. maltophilia. All compounds were not active against standard strain S. maltophilia K279a. The compound PYED-1 (pregnadiene-11-hydroxy-16α,17α-epoxy-3,20-dione-1) showed a weak effect against some S. maltophilia clinical isolates, but exhibited a synergistic effect with aminoglycosides. PYED-1 at sub-inhibitory concentrations decreased S. maltophilia biofilm formation. Quantitative real-time polymerase chain reaction (RT-qPCR) analysis demonstrated that the expression of biofilm- and virulence- associated genes (StmPr1, StmPr3, sphB, smeZ, bfmA, fsnR) was significantly suppressed after PYED-1 treatment. Interestingly, PYED-1 also repressed the expression of the genes aph (3′)-IIc, aac (6′)-Iz, and smeZ, involved in the resistance to aminoglycosides. MDPI 2020-03-02 /pmc/articles/PMC7148523/ /pubmed/32131413 http://dx.doi.org/10.3390/antibiotics9030105 Text en © 2020 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Esposito, Anna
Vollaro, Adriana
Esposito, Eliana Pia
D’Alonzo, Daniele
Guaragna, Annalisa
Zarrilli, Raffaele
De Gregorio, Eliana
Antibacterial and Antivirulence Activity of Glucocorticoid PYED-1 against Stenotrophomonas maltophilia
title Antibacterial and Antivirulence Activity of Glucocorticoid PYED-1 against Stenotrophomonas maltophilia
title_full Antibacterial and Antivirulence Activity of Glucocorticoid PYED-1 against Stenotrophomonas maltophilia
title_fullStr Antibacterial and Antivirulence Activity of Glucocorticoid PYED-1 against Stenotrophomonas maltophilia
title_full_unstemmed Antibacterial and Antivirulence Activity of Glucocorticoid PYED-1 against Stenotrophomonas maltophilia
title_short Antibacterial and Antivirulence Activity of Glucocorticoid PYED-1 against Stenotrophomonas maltophilia
title_sort antibacterial and antivirulence activity of glucocorticoid pyed-1 against stenotrophomonas maltophilia
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7148523/
https://www.ncbi.nlm.nih.gov/pubmed/32131413
http://dx.doi.org/10.3390/antibiotics9030105
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