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Clinical Utilization of Genomics Data Produced by the International Pseudomonas Aeruginosa Consortium


Clinical Utilization of Genomics Data Produced by the International Pseudomonas Aeruginosa Consortium

Luca Freschi et al. Front Microbiol.


The International Pseudomonas aeruginosa Consortium is sequencing over 1000 genomes and building an analysis pipeline for the study of Pseudomonas genome evolution, antibiotic resistance and virulence genes. Metadata, including genomic and phenotypic data for each isolate of the collection, are available through the International Pseudomonas Consortium Database ( Here, we present our strategy and the results that emerged from the analysis of the first 389 genomes. With as yet unmatched resolution, our results confirm that P. aeruginosa strains can be divided into three major groups that are further divided into subgroups, some not previously reported in the literature. We also provide the first snapshot of P. aeruginosa strain diversity with respect to antibiotic resistance. Our approach will allow us to draw potential links between environmental strains and those implicated in human and animal infections, understand how patients become infected and how the infection evolves over time as well as identify prognostic markers for better evidence-based decisions on patient care.

Keywords: Pseudomonas aeruginosa; antibiotic resistance; bacterial genome; clinical microbiology; cystic fibrosis; database; next-generation sequencing; phylogeny.


Figure 1
Figure 1
(A) Unrooted maximum likelihood tree of 389 Pseudomonas aeruginosa genomes based on SNPs within the core genome as defined by Harvest (100 bootstraps). Strains are divided into three major groups (group 1: blue, group 2: orange and group 3: green). The number of strains for each group is shown. Black circles represent strains that were already sequenced before this study while white circles represent one or more strains that were sequenced in this study. Group 3 was contracted for visualization purposes; a framed miniature of the true appearance of this tree is presented. The tree in Newick format is available as Supplementary Data Sheet 1 (B) Total coverage of the P. aeruginosa genome by the core genome for each of the three groups shown in (A), all 389 genomes (Group 1+2 + 3) and a diverse set of 55 strains from Stewart et al. (2014). (C) Total number of core genome SNPs for each of the three groups shown in (A), all 389 genomes (Group 1+2 + 3) and a diverse set of 55 strains from Stewart et al. (2014).
Figure 2
Figure 2
Heat map showing the unique distribution profiles of antibiotic resistance genes for 389 Pseudomonas aeruginosa strains (black: no sequence matching the protein; green: perfect match to known antimicrobial resistance (AMR) gene sequence; red: variant of known AMR gene sequence). The heat map was obtained by performing a Resistance Gene Identifier (RGI) analysis against reference sequences of the Comprehensive Antibiotic Resistance Database (CARD; McArthur et al., 2013). The bar plot shows in how many strains each profile was observed. On the left, proteins are grouped according to their biological function or the resistance they confer. In rare cases, more than a single copy of a resistance gene may be present within an individual strain. For those genes with resistance conferred by mutation (labeled with an asterisk), all detected mutations are known from other pathogens and may require functional verification in P. aeruginosa. Genes labeled as “putative” (“put.” in the figure) are similar to a number of known sequence variants within a family of AMR genes. All perfect matches to OXA β-lactamases are OXA-50. The complete heat map with the full set of P. aeruginosa strains is available in Supplementary Image 1. The raw data used to generate the heat map is available as Supplementary Table 1.

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