Constraint-based modeling identifies new putative targets to fight colistin-resistant A. baumannii infections

Abstract Acinetobacter baumannii is a clinical threat to human health, causing major infection outbreaks worldwide. As new drugs against Gram-negative bacteria do not seem to be forthcoming, and due to the microbial capability of acquiring multi-resistance, there is an urgent need for novel therapeu...

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Autores principales:	Luana Presta, Emanuele Bosi, Leila Mansouri, Lenie Dijkshoorn, Renato Fani, Marco Fondi
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2017
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/ad8bd12afc6c4b0f8a8764e490f98663
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spelling	oai:doaj.org-article:ad8bd12afc6c4b0f8a8764e490f986632021-12-02T15:05:19ZConstraint-based modeling identifies new putative targets to fight colistin-resistant A. baumannii infections10.1038/s41598-017-03416-22045-2322https://doaj.org/article/ad8bd12afc6c4b0f8a8764e490f986632017-06-01T00:00:00Zhttps://doi.org/10.1038/s41598-017-03416-2https://doaj.org/toc/2045-2322Abstract Acinetobacter baumannii is a clinical threat to human health, causing major infection outbreaks worldwide. As new drugs against Gram-negative bacteria do not seem to be forthcoming, and due to the microbial capability of acquiring multi-resistance, there is an urgent need for novel therapeutic targets. Here we have derived a list of new potential targets by means of metabolic reconstruction and modelling of A. baumannii ATCC 19606. By integrating constraint-based modelling with gene expression data, we simulated microbial growth in normal and stressful conditions (i.e. following antibiotic exposure). This allowed us to describe the metabolic reprogramming that occurs in this bacterium when treated with colistin (the currently adopted last-line treatment) and identify a set of genes that are primary targets for developing new drugs against A. baumannii, including colistin-resistant strains. It can be anticipated that the metabolic model presented herein will represent a solid and reliable resource for the future treatment of A. baumannii infections.Luana PrestaEmanuele BosiLeila MansouriLenie DijkshoornRenato FaniMarco FondiNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 7, Iss 1, Pp 1-12 (2017)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Luana Presta Emanuele Bosi Leila Mansouri Lenie Dijkshoorn Renato Fani Marco Fondi Constraint-based modeling identifies new putative targets to fight colistin-resistant A. baumannii infections
description	Abstract Acinetobacter baumannii is a clinical threat to human health, causing major infection outbreaks worldwide. As new drugs against Gram-negative bacteria do not seem to be forthcoming, and due to the microbial capability of acquiring multi-resistance, there is an urgent need for novel therapeutic targets. Here we have derived a list of new potential targets by means of metabolic reconstruction and modelling of A. baumannii ATCC 19606. By integrating constraint-based modelling with gene expression data, we simulated microbial growth in normal and stressful conditions (i.e. following antibiotic exposure). This allowed us to describe the metabolic reprogramming that occurs in this bacterium when treated with colistin (the currently adopted last-line treatment) and identify a set of genes that are primary targets for developing new drugs against A. baumannii, including colistin-resistant strains. It can be anticipated that the metabolic model presented herein will represent a solid and reliable resource for the future treatment of A. baumannii infections.
format	article
author	Luana Presta Emanuele Bosi Leila Mansouri Lenie Dijkshoorn Renato Fani Marco Fondi
author_facet	Luana Presta Emanuele Bosi Leila Mansouri Lenie Dijkshoorn Renato Fani Marco Fondi
author_sort	Luana Presta
title	Constraint-based modeling identifies new putative targets to fight colistin-resistant A. baumannii infections
title_short	Constraint-based modeling identifies new putative targets to fight colistin-resistant A. baumannii infections
title_full	Constraint-based modeling identifies new putative targets to fight colistin-resistant A. baumannii infections
title_fullStr	Constraint-based modeling identifies new putative targets to fight colistin-resistant A. baumannii infections
title_full_unstemmed	Constraint-based modeling identifies new putative targets to fight colistin-resistant A. baumannii infections
title_sort	constraint-based modeling identifies new putative targets to fight colistin-resistant a. baumannii infections
publisher	Nature Portfolio
publishDate	2017
url	https://doaj.org/article/ad8bd12afc6c4b0f8a8764e490f98663
work_keys_str_mv	AT luanapresta constraintbasedmodelingidentifiesnewputativetargetstofightcolistinresistantabaumanniiinfections AT emanuelebosi constraintbasedmodelingidentifiesnewputativetargetstofightcolistinresistantabaumanniiinfections AT leilamansouri constraintbasedmodelingidentifiesnewputativetargetstofightcolistinresistantabaumanniiinfections AT leniedijkshoorn constraintbasedmodelingidentifiesnewputativetargetstofightcolistinresistantabaumanniiinfections AT renatofani constraintbasedmodelingidentifiesnewputativetargetstofightcolistinresistantabaumanniiinfections AT marcofondi constraintbasedmodelingidentifiesnewputativetargetstofightcolistinresistantabaumanniiinfections
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Constraint-based modeling identifies new putative targets to fight colistin-resistant A. baumannii infections

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