Network-assisted investigation of virulence and antibiotic-resistance systems in Pseudomonas aeruginosa

Sohyun Hwang, Chan Yeong Kim, Sun Gou Ji, Junhyeok Go, Hanhae Kim, Sunmo Yang, Hye Jin Kim, Ara Cho, Sang Sun Yoon, Insuk Lee

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15 Citations (Scopus)

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.

Original languageEnglish
Article number26223
JournalScientific reports
Volume6
DOIs
Publication statusPublished - 2016 May 19

All Science Journal Classification (ASJC) codes

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    Hwang, S., Kim, C. Y., Ji, S. G., Go, J., Kim, H., Yang, S., Kim, H. J., Cho, A., Yoon, S. S., & Lee, I. (2016). Network-assisted investigation of virulence and antibiotic-resistance systems in Pseudomonas aeruginosa. Scientific reports, 6, [26223]. https://doi.org/10.1038/srep26223