A Systems-Level Approach for Investigating Pseudomonas aeruginosa Biofilm Formation

Zhaobin Xu, Xin Fang, Thomas Keith Wood, Zuyi Jacky Huang

Research output: Contribution to journalArticle

17 Citations (Scopus)

Abstract

Prevention of the initiation of biofilm formation is the most important step for combating biofilm-associated pathogens, as the ability of pathogens to resist antibiotics is enhanced 10 to 1000 times once biofilms are formed. Genes essential to bacterial growth in the planktonic state are potential targets to treat biofilm-associated pathogens. However, the biofilm formation capability of strains with mutations in these essential genes must be evaluated, since the pathogen might form a biofilm before it is eliminated. In order to address this issue, this work proposes a systems-level approach to quantifying the biofilm formation capability of mutants to determine target genes that are essential for bacterial metabolism in the planktonic state but do not induce biofilm formation in their mutants. The changes of fluxes through the reactions associated with the genes positively related to biofilm formation are used as soft sensors in the flux balance analysis to quantify the trend of biofilm formation upon the mutation of an essential gene. The essential genes whose mutants are predicted not to induce biofilm formation are regarded as gene targets. The proposed approach was applied to identify target genes to treat Pseudomonas aeruginosa infections. It is interesting to find that most essential gene mutants exhibit high potential to induce the biofilm formation while most non-essential gene mutants do not. Critically, we identified four essential genes, lysC, cysH, adk, and galU, that constitute gene targets to treat P. aeruginosa. They have been suggested by existing experimental data as potential drug targets for their crucial role in the survival or virulence of P. aeruginosa. It is also interesting to find that P. aeruginosa tends to survive the essential-gene mutation treatment by mainly enhancing fluxes through 8 metabolic reactions that regulate acetate metabolism, arginine metabolism, and glutamate metabolism.

Original languageEnglish (US)
Article numbere57050
JournalPloS one
Volume8
Issue number2
DOIs
StatePublished - Feb 22 2013

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Biofilms
Pseudomonas aeruginosa
biofilm
Genes
Essential Genes
Pathogens
Metabolism
mutants
metabolism
genes
pathogens
arginine glutamate
mutation
Fluxes
Mutation
Bacterial Genes
Pseudomonas Infections
essential genes
glutamates
arginine

All Science Journal Classification (ASJC) codes

  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)

Cite this

Xu, Zhaobin ; Fang, Xin ; Wood, Thomas Keith ; Huang, Zuyi Jacky. / A Systems-Level Approach for Investigating Pseudomonas aeruginosa Biofilm Formation. In: PloS one. 2013 ; Vol. 8, No. 2.
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A Systems-Level Approach for Investigating Pseudomonas aeruginosa Biofilm Formation. / Xu, Zhaobin; Fang, Xin; Wood, Thomas Keith; Huang, Zuyi Jacky.

In: PloS one, Vol. 8, No. 2, e57050, 22.02.2013.

Research output: Contribution to journalArticle

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