The Genome of Burkholderia cenocepacia J2315, an Epidemic Pathogen of Cystic Fibrosis Patients

Abstract

Bacterial infections of the lungs of cystic fibrosis (CF) patients cause major complications in the treatment of this common genetic disease.Burkholderia cenocepacia infection is particularly problematic since this organism has high levels of antibiotic resistance, making it difficult to eradicate; the resulting chronic infections are associated with severe declines in lung function and increased mortality rates. B. cenocepacia strain J2315 was isolated from a CF patient and is a member of the epidemic ET12 lineage that originated in Canada or the United Kingdom and spread to Europe. The 8.06-Mb genome of this highly transmissible pathogen comprises three circular chromosomes and a plasmid and encodes a broad array of functions typical of this metabolically versatile genus, as well as numerous virulence and drug resistance functions. Although B. cenocepacia strains can be isolated from soil and can be pathogenic to both plants and man, J2315 is representative of a lineage of B. cenocepacia rarely isolated from the environment and which spreads between CF patients. Comparative analysis revealed that ca. 21% of the genome is unique in comparison to other strains of B. cenocepacia, highlighting the genomic plasticity of this species. Pseudogenes in virulence determinants suggest that the pathogenic response of J2315 may have been recently selected to promote persistence in the CF lung. The J2315 genome contains evidence that its unique and highly adapted genetic content has played a significant role in its success as an epidemic CF pathogen.

Analysis of genomic characters reveals that four distinct gene clusters are correlated with different functions in Burkholderia cenocepacia AU 1054

“…S1). Moreover, there were more than 75 % orthologous genes identified among these three B. cenocepacia species, and they showed a syntenic relationship among the three chromosomes, which directly determined the similar genomic characters among them (Holden et al 2009). Furthermore, it was surprising to observe that the distribution pattern of the other four species within the same genus also showed similarity to one other, even at the base composition of the third codon position (Supplementary Fig.…”

“…S1). Like many other species of BCC whose GC content varies from 61 % to 68 %, B. cenocepacia AU 1054 is a species that has intermediate GC content as well (67 %; Higareda et al 2012;Holden et al 2009). The similar base usage pattern among these species was reasonable because genomes with a close GC content lean toward similar base composition patterns (Chen and Zhang 2003).…”

“…Three reasons could be responsible for this phenomenon. First, there was a definite shift from a soil saprophyte to a host-associated pathogen lifestyle in B. cenocepacia (Holden et al 2009), which indicates that this species experienced a dramatic environmental change in the evolutionary history. Essential genes and survival-associated genes are widely spread among the chromosomes, which suggests that a multi-chromosome structure of the BCC is essential for their fitness in a given environment .…”

“…In B. cenocepacia , HGT cannot lead to codon usage bias between any two chromosomes, although it is one of the two most important factors that affect codon usage. HTGs acquired from other bacteria or from the host have substantially contributed to genomic plasticity in B. cenocepacia (Holden et al 2009;Mahenthiralingam et al 2005). Additionally, B. cenocepacia is a species that is successful at balancing the stability and plasticity of the genome organization (Mohn and Schübeler 2009).…”

“…this species to transmit infections among CF patients and that also make it difficult for clinical prognosis and cures (Holden et al 2009;Ortega et al 2005). It is known that most of the bacterial genomes are composed of a single typical chromosome.…”