Cystic Fibrosis (CF) is a genetic disorder that results in impaired mucociliary clearance of inhaled microorganisms. Over time, the airways of CF patients become colonised with different microorganisms, eventually resulting in infections that cannot be eradicated. Most common is Pseudomonas aeruginosa, which can establish a chronic infection despite aggressive antibiotic therapy. Phenotypic hallmarks of chronic CF P. aeruginosa isolates include mucoid colonies, multi-antibiotic resistance, slow growth, auxotrophy and loss of virulence factors and motility.
Burkholderia pseudomallei is an opportunistic pathogen that causes melioidosis, a potentially fatal disease with usually an acute presentation. Melioidosis is being increasingly described in CF patients travelling to or living in melioidosis-endemic regions. Clinical features of melioidosis in CF patients range from acute infection with rapid deterioration, to a slow, progressive deterioration in lung function and even apparent subclinical colonisation with B. pseudomallei.
We have commenced genomic analyses of paired B. pseudomallei isolates from seven chronically-infected CF patients, collected between 4 and 47 months apart. We observed mutations in 5/7 instances. In one case, genetic adaptations included multi-antibiotic resistance, along with deleterious mutation of the virulence factor ompA (a surface protein), and enzymes involved in fatty acid synthesis. In 4/5 cases, global transcriptional regulators were adversely affected either by single nucleotide polymorphisms (SNPs) or deletions. Such mutations are anticipated to have genome-wide transcriptional implications. SNPs affecting fabF, which encodes fatty acid biosynthesis, were observed in two isolates, suggesting that this gene plays a role in progression to chronic infection. Reductive evolution was observed in two instances, resulting in the loss of 30 and 125 genes. Overall, B. pseudomallei showed similar evolutionary patterns to other chronic infections including down-regulation of virulence, antibiotic resistance, changes in genome wide regulators and reduction in genome size. These findings indicate multiple B. pseudomallei adaptation strategies to the CF lung environment.