Abstract

Pseudomonas aeruginosa is an opportunistic pathogen implicated in a myriad of infections and a leading pathogen responsible for mortality in patients with cystic fibrosis (CF). Horizontal transfers of genes among the microorganisms living within CF patients have led to highly virulent and multi-drug resistant strains such as the Liverpool epidemic strain of P. aeruginosa, namely the LESB58 strain that has the propensity to acquire virulence and antibiotic resistance genes. Often these genes are acquired in large clusters, referred to as “genomic islands (GIs).” To decipher GIs and understand their contributions to the evolution of virulence and antibiotic resistance in P. aeruginosa LESB58, we utilized a recursive segmentation and clustering procedure, presented here as a genome-mining tool, “GEMINI.” GEMINI was validated on experimentally verified islands in the LESB58 strain before examining its potential to decipher novel islands. Of the 6062 genes in P. aeruginosa LESB58, 596 genes were identified to be resident on 20 GIs of which 12 have not been previously reported. Comparative genomics provided evidence in support of our novel predictions. Furthermore, GEMINI unraveled the mosaic structure of islands that are composed of segments of likely different evolutionary origins, and demonstrated its ability to identify potential strain biomarkers. These newly found islands likely have contributed to the hyper-virulence and multidrug resistance of the Liverpool epidemic strain of P. aeruginosa.

Highlights

  • Pseudomonas aeruginosa dwells in diverse environments including soil, water, and air

  • The original Markovian Jensen–Shannon Divergence (MJSD)-based segmentation and clustering method was shown to be effective in localizing the genomic islands (GIs) (Azad and Li, 2013), its ability to decipher the mosaic structure of GIs was never harnessed for understanding the contribution of the mosaicism in pathogenicity

  • We hypothesized that the unique mosaic GIs in this strain would be unraveled using GEMINI. (b) Previous studies had validated four GIs in LESB58 using wet-lab assays, and this genome provided an opportunity to benchmark GEMINI against the other GI prediction methods. (c) The availability of a large number of closed genomes provided an opportunity to compare with the first identified epidemic P. aeruginosa isolate, the LESB58 strain, in order to assess the genotypic differences between the epidemic and non-epidemic strains

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Summary

Introduction

Pseudomonas aeruginosa dwells in diverse environments including soil, water, and air. P. aeruginosa strains have been isolated from medical equipment such as catheters (Nickel et al, 1985). P. aeruginosa strains have multifarious metabolic capabilities, including the ability to degrade gasoline, kerosene, and diesel (Wongsa et al, 2004). P. aeruginosa causes post-operative infections as well as infections in other immuno-compromised conditions, such as burn wounds and cancer (Sato et al, 1988; Rolston and Bodey, 1992). It is well known for causing morbidity and mortality in patients with cystic fibrosis

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