title: Network-assisted investigation of virulence and antibiotic-resistance systems in Pseudomonas aeruginosa.
abstract: Pseudomonas aeruginosa is a Gram-negative bacterium of clinical significance. Although the genome of PAO1, a prototype strain of P. aeruginosa, has been extensively studied, approximately one-third of the functional genome remains unknown. With the emergence of antibiotic-resistant strains of P. aeruginosa, there is an urgent need to develop novel antibiotic and anti-virulence strategies, which may be facilitated by an approach that explores P. aeruginosa gene function in systems-level models. Here, we present a genome-wide functional network of P. aeruginosa genes, PseudomonasNet, which covers 98% of the coding genome, and a companion web server to generate functional hypotheses using various network-search algorithms. We demonstrate that PseudomonasNet-assisted predictions can effectively identify novel genes involved in virulence and antibiotic resistance. Moreover, an antibiotic-resistance network based on PseudomonasNet reveals that P. aeruginosa has common modular genetic organisations that confer increased or decreased resistance to diverse antibiotics, which accounts for the pervasiveness of cross-resistance across multiple drugs. The same network also suggests that P. aeruginosa has developed mechanism of trade-off in resistance across drugs by altering genetic interactions. Taken together, these results clearly demonstrate the usefulness of a genome-scale functional network to investigate pathogenic systems in P. aeruginosa.
authors.affiliation: Department of Biotechnology, College of Life Science and Biotechnology, Yonsei University, Seoul, 120-749, Korea.|Center for Systems and Synthetic Biology, University of Texas at Austin, Austin, TX 78712, USA.
authors.forename: Sohyun
authors.initials: S
authors.lastname: Hwang
authors.affiliation: Department of Biotechnology, College of Life Science and Biotechnology, Yonsei University, Seoul, 120-749, Korea.
authors.forename: Chan Yeong
authors.initials: CY
authors.lastname: Kim
authors.affiliation: Department of Biotechnology, College of Life Science and Biotechnology, Yonsei University, Seoul, 120-749, Korea.
authors.forename: Sun-Gou
authors.initials: SG
authors.lastname: Ji
authors.affiliation: Department of Microbiology and Immunology, Brain Korea 21 PLUS Project for Medical Science, Yonsei University College of Medicine, Seoul, 120-749, Korea.
authors.forename: Junhyeok
authors.initials: J
authors.lastname: Go
authors.affiliation: Department of Biotechnology, College of Life Science and Biotechnology, Yonsei University, Seoul, 120-749, Korea.
authors.forename: Hanhae
authors.initials: H
authors.lastname: Kim
authors.affiliation: Department of Biotechnology, College of Life Science and Biotechnology, Yonsei University, Seoul, 120-749, Korea.
authors.forename: Sunmo
authors.initials: S
authors.lastname: Yang
authors.affiliation: Department of Microbiology and Immunology, Brain Korea 21 PLUS Project for Medical Science, Yonsei University College of Medicine, Seoul, 120-749, Korea.
authors.forename: Hye Jin
authors.initials: HJ
authors.lastname: Kim
authors.affiliation: Department of Biotechnology, College of Life Science and Biotechnology, Yonsei University, Seoul, 120-749, Korea.
authors.forename: Ara
authors.initials: A
authors.lastname: Cho
authors.affiliation: Department of Microbiology and Immunology, Brain Korea 21 PLUS Project for Medical Science, Yonsei University College of Medicine, Seoul, 120-749, Korea.
authors.forename: Sang Sun
authors.initials: SS
authors.lastname: Yoon
authors.affiliation: Department of Biotechnology, College of Life Science and Biotechnology, Yonsei University, Seoul, 120-749, Korea.
authors.forename: Insuk
authors.initials: I
authors.lastname: Lee
mesh_terms: D019295:Computational Biology; D024881:Drug Resistance, Bacterial; D053263:Gene Regulatory Networks; D005798:Genes, Bacterial; D011550:Pseudomonas aeruginosa / Q000187:drug effects* / Q000472:pathogenicity*; D049490:Systems Biology; D037521:Virulence Factors / Q000032:analysis*
chemical_list: D037521:Virulence Factors