Pangenome-wide and molecular evolution analyses of thePseudomonas aeruginosa species

Abstract

30Background. Drug treatments and vaccine designs against the opportunistic human pathogen Pseudomonas aeruginosa have multiple issues, all associated with the diverse genetic traits present in this pathogen, ranging from multi-drug resistant genes to the molecular machinery for the biosynthesis of biofilms. Several candidate vaccines against P. aeruginosa have been developed, which target the outer membrane proteins; however, 35 major issues arise when attempting to establish complete protection against this pathogen due to its presumably genotypic variation at the strain level. To shed light on this concern, we proposed this study to assess the P. aeruginosa pangenome and its molecular evolution across multiple strains. Results. The P. aeruginosa pangenome was estimated to contain almost 17,000 non-redundant genes, and approximately 15% of these constituted the core 40 genome. Functional analyses of the accessory genome indicated a wide presence of genetic elements directly associated with pathogenicity. An in-depth molecular evolution analysis revealed the full landscape of selection forces acting on the P. aeruginosa pangenome, in which purifying selection drives evolution in the genome of this human pathogen. We also detected distinctive positive selection in a wide variety of outer membrane proteins, with 45 the data supporting the concept of substantial genetic variation in proteins probably recognized as antigens. Approaching the evolutionary information of genes under extremely positive selection, we designed a new Multi-Locus Sequencing Typing assay for an informative, rapid, and cost-effective genotyping of P. aeruginosa clinical isolates.Conclusions. We report the unprecedented pangenome characterization of P. aeruginosa 50 on a large scale, which included almost 200 bacterial genomes from one single species and a molecular evolutionary analysis at the pangenome scale. Evolutionary information presented here provides a clear explanation of the issues associated with the use of protein

Modeling the control of bacterial infections via antibiotic-induced proviruses

“…Comparative genomics among closely related bacterial strains has uncovered a plethora of proviruses of both temperate and chronic lifestyles [22][23][24]. The large genome of the opportunistic pathogen P. aeruginosa is no exception [25][26][27]. Each sequenced strain reveals multiple proviral genomes of both the temperate and chronic lifestyles, each in both active and inactive (latent) forms [28].…”

Multi-omics approach identifies novel pathogen-derived prognostic biomarkers in patients withPseudomonas aeruginosabloodstream infection

“…Given the huge diversity of bacterial genomes and functional capacities even within one species, the pathogen itself could account for 4 unexplained heterogeneity in the clinical course and outcome of sepsis. Recently, the pangenome of the species P. aeruginosa was estimated to contain more than 16,000 non-redundant genes, while only 15% of these genes were present in all strains forming the core genome (Mosquera-Rendon et al 2016). Of particular interest are prognostic bacterial biomarkers that can indicate the risk of a fatal outcome in septic patients, thus providing guidance in therapy and improved management of patient monitoring.…”

Pseudomonas aeruginosa blood stream infections: clinical and molecular epidemiology, virulence and outcome

“…Mosquera-Rendon et al reported on the pangenome characterisation of 200 P. aeruginosa bacterial genomes. They found that approximately 60% of the P. aeruginosa genome was variable across the strains [110]. In this accessory genome, Pohl et al identified genes from other bacterial species [111].…”

“…With the utilisation of whole genome sequencing we have been able to gain greater understanding of the genome of P. aeruginosa. It is a large genome of 6.3 MB, containing on average more than 6175 genes [110]. The core genome represents on average 88% of the genome [112].…”