Abstract

Acinetobacter baumannii has become an urgent clinical threat due to the recent emergence of multi-drug resistant strains. There is thus a significant need to discover new therapeutic targets in this organism. One means for doing so is through the use of high-quality genome-scale reconstructions. Well-curated and accurate genome-scale models (GEMs) of A. baumannii would be useful for improving treatment options. We present an updated and improved genome-scale reconstruction of A. baumannii AYE, named iCN718, that improves and standardizes previous A. baumannii AYE reconstructions. iCN718 has 80% accuracy for predicting gene essentiality data and additionally can predict large-scale phenotypic data with as much as 89% accuracy, a new capability for an A. baumannii reconstruction. We further demonstrate that iCN718 can be used to analyze conserved metabolic functions in the A. baumannii core genome and to build strain-specific GEMs of 74 other A. baumannii strains from genome sequence alone. iCN718 will serve as a resource to integrate and synthesize new experimental data being generated for this urgent threat pathogen.

Highlights

  • Acinetobacter baumannii has recently emerged as a deadly nosocomial threat with rising rates of both infection and antibiotic resistance

  • Pathogenic A. baumannii antibiotic resistance has risen from a susceptible level in the 1960s to extended and pan-drug resistant today (Peleg et al, 2008)

  • We found that the AbyMBEL891 reconstruction could be updated and improved in three main areas: (1) standardization of reaction and metabolite identifiers to increase the tractability of the network, (2) mass and charge balance metabolic reactions, and (3) transport processes

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Summary

Introduction

Acinetobacter baumannii has recently emerged as a deadly nosocomial threat with rising rates of both infection and antibiotic resistance. Reports using data from hospital-based surveillance studies as well as from the Infectious Diseases Society of America have begun to refer to a dangerous group of nosocomial pathogens, including A. baumannii, as “ESKAPE pathogens” (Rice, 2008). Organisms of the genus Acinetobacter inhabit a wide variety of environments, ranging from humans to water and soil (Vallenet et al, 2008). These diverse environmental niches are reflected in the genomic content of the organisms as well as their metabolic capabilities. The need for new treatment targets and strategies is dire

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