Comparative genomics of Burkholderia multivorans, a ubiquitous pathogen with a highly conserved genomic structure

Abstract

The natural environment serves as a reservoir of opportunistic pathogens. A well-established method for studying the epidemiology of such opportunists is multilocus sequence typing, which in many cases has defined strains predisposed to causing infection. Burkholderia multivorans is an important pathogen in people with cystic fibrosis (CF) and its epidemiology suggests that strains are acquired from non-human sources such as the natural environment. This raises the central question of whether the isolation source (CF or environment) or the multilocus sequence type (ST) of B. multivorans better predicts their genomic content and functionality. We identified four pairs of B. multivorans isolates, representing distinct STs and consisting of one CF and one environmental isolate each. All genomes were sequenced using the PacBio SMRT sequencing technology, which resulted in eight high-quality B. multivorans genome assemblies. The present study demonstrated that the genomic structure of the examined B. multivorans STs is highly conserved and that the B. multivorans genomic lineages are defined by their ST. Orthologous protein families were not uniformly distributed among chromosomes, with core orthologs being enriched on the primary chromosome and ST-specific orthologs being enriched on the second and third chromosome. The ST-specific orthologs were enriched in genes involved in defense mechanisms and secondary metabolism, corroborating the strain-specificity of these virulence characteristics. Finally, the same B. multivorans genomic lineages occur in both CF and environmental samples and on different continents, demonstrating their ubiquity and evolutionary persistence.

Comparative Genomics of Environmental and Clinical Burkholderia cenocepacia Strains Closely Related to the Highly Transmissible Epidemic ET12 Lineage

“…The B. cenocepacia species is characterized by a large variety of ecological niches, from patient-associated to environmental niches. Although some studies have shown that clinical strains of B. cenocepacia have a higher virulence than environmental strains ( Pirone et al, 2008 ; Bevivino et al, 2012 ), the distinction between clinical and environmental strains based on phenotypic or genotypic criteria remains difficult ( Bevivino et al, 2002 ; Peeters et al, 2017 ). Indeed, to our knowledge, strains belonging to the ET12 lineage had not yet been isolated from a non-clinical environment ( Baldwin et al, 2007 ).…”

“…The Bcc (originally described as Pseudomonas cepacia ) comprises 20 taxonomically related species frequently isolated in water or soil, including plant-associated environments ( Ramette et al, 2005 ; De Smet et al, 2015 ). Burkholderia multivorans and B. cenocepacia (formerly Genomovar II and III, respectively) are the most clinically frequent members of Bcc, representing from 50% up to 80% of the infections caused by this complex ( Mahenthiralingam et al, 2002 ; Holden et al, 2009 ; Peeters et al, 2017 ). Unlike other opportunistic pathogens isolated from CF patients (e.g., Haemophilus influenzae or P. aeruginosa ), members of the Bcc could lead to the “ cepacia syndrome.” This syndrome is characterized by a rapid clinical deterioration due to necrotizing pneumonia or sepsis, resulting in early death ( Isles et al, 1984 ; Gibson et al, 2003 ).…”

“…DNA–DNA hybridization and phylogenetic analysis of the recA gene revealed the presence of four distinct recA lineages within B. cenocepacia , i.e., genomovar IIIA to IIID ( Vandamme et al, 2003 ). Even though no clear distinction has been established between clinical and environmental Bcc strains on the basis of phenotypic or genotypic criteria ( Bevivino et al, 2002 ; Peeters et al, 2017 ), B. cenocepacia strains isolated from CF patients seem to be more invasive and more virulent than environmental strains ( Pirone et al, 2008 ; Bevivino et al, 2012 ). Moreover, B. cenocepacia IIIA strains were rarely found outside of human infections in comparison to other B. cenocepacia and the Bcc ( Baldwin et al, 2007 ).…”

Phylogeographic, genomic, and meropenem susceptibility analysis of Burkholderia ubonensis

“…ubonensis MLST genotypes obtained using both the B . pseudomallei and Bcc MLST schemes with phylogenomic assignment to determine whether the STs reflected isolate relatedness on the genome level [ 49 ], or whether homoplasy was evident among STs as has been observed with certain B . pseudomallei STs [ 50 , 51 ].…”

Burkholderia cepacia Complex Species Differ in the Frequency of Variation of the Lipopolysaccharide O-Antigen Expression During Cystic Fibrosis Chronic Respiratory Infection

“…Remarkably, B. cenocepacia and B. multivorans cell lysates are more potent stimulators of pro-inflammatory cytokines compared with those from other Bcc species (De Soyza et al, 2004). However, even though the prevalence of B. multivorans has recently replaced B. cenocepacia in several countries (Baldwin et al, 2008; Lipuma, 2010; Medina-Pascual et al, 2012; Peeters et al, 2017), it is clear that B. cenocepacia recA lineage IIIA remains the most dominant species (Manno et al, 2004; Nunvar et al, 2017; Scoffone et al, 2017; Teri et al, 2018). Remarkably, the particularly destructive nature of B. cenocepacia recA group IIIA infections in CF patients when compared with other Bcc bacteria has been reported (Manno et al, 2004; Zlosnik et al, 2015).…”