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Systems biology studies in Pseudomonas aeruginosa PA01 to understand their role in biofilm formation and multidrug efflux pumps.

Abstract：

:The antimicrobial resistance (AMR) exhibited against broad spectrum and new generation antibiotics used for Pseudomonas infections is a major threat and renders the treatment ineffective. In our present study, we have used a computational approach to understand various drug resistance mechanisms which contribute to Multi-Drug Resistance (MDR) in P. aeruginosa. The interaction network of 60 AMR genes along with the 337 functional interactions was analyzed. Functional enrichment analysis of AMR genes has shown that the genes in the network are mainly associated with efflux pump mechanisms, alginate biosynthesis, biofilm formation, and ampC beta-lactamase biosynthesis. Interestingly, the genes phoP, phoQ, and cat genes are observed to have roles in more than one drug-resistant mechanism. The genes phoP and phoQ apart from their role in two-component regulatory systems also play major roles in multidrug efflux pumps and alteration in drug target. The gene cat involves in alteration of drug target and enzymatic inactivation. The interaction network analysis has shown that the AMR genes oprJ, oprM, oprN, ampC, gyrA, mexA, oprD, mexB and nfxB have higher number of direct interactors and they are considered as the hub nodes in the network and these genes can be used as potential drug targets for developing new drugs. The results from our study will be helpful in better understanding of the antibiotic resistance mechanisms in P. aeruginosa. The gene targets reported, can be used for new drug discovery against Pseudomonas infections.

journal_name

Microb Pathog

journal_title

Microbial pathogenesis

authors

Miryala SK,Anbarasu A,Ramaiah S

doi

10.1016/j.micpath.2019.103668

subject

Has Abstract

pub_date

2019-11-01 00:00:00

pages

103668

eissn

0882-4010

issn

1096-1208

pii

S0882-4010(19)30481-4

journal_volume

136

pub_type

杂志文章

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