Abstract

Pseudomonas aeruginosa is an opportunistic bacterial pathogen able to thrive in highly diverse ecological niches and to infect compromised patients. Its genome exhibits a mosaic structure composed of a core genome into which accessory genes are inserted en bloc at specific sites. The size and the content of the core genome are open for debate as their estimation depends on the set of genomes considered and the pipeline of gene detection and clustering. Here, we redefined the size and the content of the core genome of P. aeruginosa from fully re-analyzed genomes of 17 reference strains. After the optimization of gene detection and clustering parameters, the core genome was defined at 5,233 orthologs, which represented ~ 88% of the average genome. Extrapolation indicated that our panel was suitable to estimate the core genome that will remain constant even if new genomes are added. The core genome contained resistance determinants to the major antibiotic families as well as most metabolic, respiratory, and virulence genes. Although some virulence genes were accessory, they often related to conserved biological functions. Long-standing prophage elements were subjected to a genetic drift to eventually display a G+C content as higher as that of the core genome. This contrasts with the low G+C content of highly conserved ribosomal genes. The conservation of metabolic and respiratory genes could guarantee the ability of the species to thrive on a variety of carbon sources for energy in aerobiosis and anaerobiosis. Virtually all the strains, of environmental or clinical origin, have the complete toolkit to become resistant to the major antipseudomonal compounds and possess basic pathogenic mechanisms to infect humans. The knowledge of the genes shared by the majority of the P. aeruginosa isolates is a prerequisite for designing effective therapeutics to combat the wide variety of human infections.

Highlights

  • Pseudomonas aeruginosa is a Gram-negative bacterium that causes significant mortality and morbidity among compromised patients, including those suffering from cystic fibrosis

  • A thorough understanding of the networks of genes that are shared by the majority of the P. aeruginosa isolates is crucial for the design of effective therapeutics to combat the wide variety of human infections

  • The seed of each cluster served as a proxy for pairwise comparison and the whole matrix went through a classification process with the MCL clustering program

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Summary

Introduction

Pseudomonas aeruginosa is a Gram-negative bacterium that causes significant mortality and morbidity among compromised patients, including those suffering from cystic fibrosis. The treatment of infected patients is complicated by the extraordinary capacity of this bacterium to develop resistance to almost all antibiotics, through the selection of mutations in chromosomal genes and the spread of horizontally acquired resistance [1]. P. aeruginosa has a non-clonal structure, a few sequence types (STs) called ‘high-risk clones’ are widely distributed and frequently encountered [4]. The genome of P. aeruginosa is large (> 6 Mbp) and exhibits a mosaic structure composed of a large core genome into which accessory genes are inserted en bloc at specific sites, called region of genomic plasticity (RGP) [5, 6]. A thorough understanding of the networks of genes that are shared by the majority of the P. aeruginosa isolates is crucial for the design of effective therapeutics to combat the wide variety of human infections

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