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

Authors
 Sohyun Hwang  ;  Chan Yeong Kim  ;  Sun-Gou Ji  ;  Junhyeok Go  ;  Hanhae Kim  ;  Sunmo Yang  ;  Hye Jin Kim  ;  Ara Cho  ;  Sang Sun Yoon  ;  Insuk Lee 
Citation
 SCIENTIFIC REPORTS, Vol.6 : 26223, 2016 
Journal Title
SCIENTIFIC REPORTS
Issue Date
2016
MeSH
Computational Biology ; Drug Resistance, Bacterial* ; Gene Regulatory Networks ; Genes, Bacterial ; Pseudomonas aeruginosa/drug effects* ; Pseudomonas aeruginosa/pathogenicity* ; Systems Biology ; Virulence Factors/analysis*
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.
DOI
10.1038/srep26223
Appears in Collections:
1. College of Medicine (의과대학) > Dept. of Microbiology (미생물학교실) > 1. Journal Papers
Yonsei Authors
Yoon, Sang Sun(윤상선) ORCID logo https://orcid.org/0000-0003-2979-365X
URI
https://ir.ymlib.yonsei.ac.kr/handle/22282913/146899
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