A systems biology approach to drug targets in Pseudomonas aeruginosa biofilm.

Antibiotic resistance is an increasing problem in the health care system and we are in a constant race with evolving bacteria. Biofilm-associated growth is thought to play a key role in bacterial adaptability and antibiotic resistance. We employed a systems biology approach to identify candidate dru...

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Autores principales:	Gunnar Sigurdsson, Ronan M T Fleming, Almut Heinken, Ines Thiele
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2012
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/92a5542f3cf448ddb55eb2b4eafcf17a
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spelling	oai:doaj.org-article:92a5542f3cf448ddb55eb2b4eafcf17a2021-11-18T07:22:06ZA systems biology approach to drug targets in Pseudomonas aeruginosa biofilm.1932-620310.1371/journal.pone.0034337https://doaj.org/article/92a5542f3cf448ddb55eb2b4eafcf17a2012-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/22523548/?tool=EBIhttps://doaj.org/toc/1932-6203Antibiotic resistance is an increasing problem in the health care system and we are in a constant race with evolving bacteria. Biofilm-associated growth is thought to play a key role in bacterial adaptability and antibiotic resistance. We employed a systems biology approach to identify candidate drug targets for biofilm-associated bacteria by imitating specific microenvironments found in microbial communities associated with biofilm formation. A previously reconstructed metabolic model of Pseudomonas aeruginosa (PA) was used to study the effect of gene deletion on bacterial growth in planktonic and biofilm-like environmental conditions. A set of 26 genes essential in both conditions was identified. Moreover, these genes have no homology with any human gene. While none of these genes were essential in only one of the conditions, we found condition-dependent genes, which could be used to slow growth specifically in biofilm-associated PA. Furthermore, we performed a double gene deletion study and obtained 17 combinations consisting of 21 different genes, which were conditionally essential. While most of the difference in double essential gene sets could be explained by different medium composition found in biofilm-like and planktonic conditions, we observed a clear effect of changes in oxygen availability on the growth performance. Eight gene pairs were found to be synthetic lethal in oxygen-limited conditions. These gene sets may serve as novel metabolic drug targets to combat particularly biofilm-associated PA. Taken together, this study demonstrates that metabolic modeling of human pathogens can be used to identify oxygen-sensitive drug targets and thus, that this systems biology approach represents a powerful tool to identify novel candidate antibiotic targets.Gunnar SigurdssonRonan M T FlemingAlmut HeinkenInes ThielePublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 7, Iss 4, p e34337 (2012)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Gunnar Sigurdsson Ronan M T Fleming Almut Heinken Ines Thiele A systems biology approach to drug targets in Pseudomonas aeruginosa biofilm.
description	Antibiotic resistance is an increasing problem in the health care system and we are in a constant race with evolving bacteria. Biofilm-associated growth is thought to play a key role in bacterial adaptability and antibiotic resistance. We employed a systems biology approach to identify candidate drug targets for biofilm-associated bacteria by imitating specific microenvironments found in microbial communities associated with biofilm formation. A previously reconstructed metabolic model of Pseudomonas aeruginosa (PA) was used to study the effect of gene deletion on bacterial growth in planktonic and biofilm-like environmental conditions. A set of 26 genes essential in both conditions was identified. Moreover, these genes have no homology with any human gene. While none of these genes were essential in only one of the conditions, we found condition-dependent genes, which could be used to slow growth specifically in biofilm-associated PA. Furthermore, we performed a double gene deletion study and obtained 17 combinations consisting of 21 different genes, which were conditionally essential. While most of the difference in double essential gene sets could be explained by different medium composition found in biofilm-like and planktonic conditions, we observed a clear effect of changes in oxygen availability on the growth performance. Eight gene pairs were found to be synthetic lethal in oxygen-limited conditions. These gene sets may serve as novel metabolic drug targets to combat particularly biofilm-associated PA. Taken together, this study demonstrates that metabolic modeling of human pathogens can be used to identify oxygen-sensitive drug targets and thus, that this systems biology approach represents a powerful tool to identify novel candidate antibiotic targets.
format	article
author	Gunnar Sigurdsson Ronan M T Fleming Almut Heinken Ines Thiele
author_facet	Gunnar Sigurdsson Ronan M T Fleming Almut Heinken Ines Thiele
author_sort	Gunnar Sigurdsson
title	A systems biology approach to drug targets in Pseudomonas aeruginosa biofilm.
title_short	A systems biology approach to drug targets in Pseudomonas aeruginosa biofilm.
title_full	A systems biology approach to drug targets in Pseudomonas aeruginosa biofilm.
title_fullStr	A systems biology approach to drug targets in Pseudomonas aeruginosa biofilm.
title_full_unstemmed	A systems biology approach to drug targets in Pseudomonas aeruginosa biofilm.
title_sort	systems biology approach to drug targets in pseudomonas aeruginosa biofilm.
publisher	Public Library of Science (PLoS)
publishDate	2012
url	https://doaj.org/article/92a5542f3cf448ddb55eb2b4eafcf17a
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_version_	1718423547976613888

A systems biology approach to drug targets in Pseudomonas aeruginosa biofilm.

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