Abstract
Pulmonary colonization of cystic fibrosis (CF) patients with Burkholderia cenocepacia or other bacteria of the Burkholderia cepacia complex (Bcc) is associated with worse prognosis and increased risk of death. During colonization, the bacteria may evolve under the stressing selection pressures exerted in the CF lung, in particular, those resulting from challenges of the host immune defenses, antimicrobial therapy, nutrient availability and oxygen limitation. Understanding the adaptive mechanisms that promote successful colonization and long-term survival of B. cenocepacia in the CF lung is essential for an improved therapeutic outcome of chronic infections. To get mechanistic insights into these adaptive strategies a transcriptomic analysis, based on DNA microarrays, was explored in this study. The genomic expression levels in two clonal variants isolated during long-term colonization of a CF patient who died from the cepacia syndrome were compared. One of the isolates examined, IST439, is the first B. cenocepacia isolate retrieved from the patient and the other isolate, IST4113, was obtained three years later and is more resistant to different classes of antimicrobials. Approximately 1000 genes were found to be differently expressed in the two clonal variants reflecting a marked reprogramming of genomic expression. The up-regulated genes in IST4113 include those involved in translation, iron uptake (in particular, in ornibactin biosynthesis), efflux of drugs and in adhesion to epithelial lung tissue and to mucin. Alterations related with adaptation to the nutritional environment of the CF lung and to an oxygen-limited environment are also suggested to be a key feature of transcriptional reprogramming occurring during long-term colonization, antibiotic therapy and the progression of the disease.
Highlights
The Burkholderia cepacia complex (Bcc) is a heterogeneous group of bacteria comprising at least 17 closely related species that are ubiquitous, metabolically versatile and can cause chronic opportunistic infections in immunocompromised patients and in patients with cystic fibrosis (CF) [1]
No other gene located in the described genomic islands present in B. cenocepacia J2315 genome was found to be differently expressed in the clonal variants examined, consistent with the concept that B. cenocepacia pathoadaptation to CF lung relates with modifications occurring at the level of the inherent traits of the bacterium instead of being acquired through mobile genetic elements [24]
These clonal variants may result from genetic adaptation and selection pressures exerted by the host environment, in particular, from the challenges imposed by the immune defences, antimicrobial therapy, nutrient availability and oxygen limitation
Summary
The Burkholderia cepacia complex (Bcc) is a heterogeneous group of bacteria comprising at least 17 closely related species that are ubiquitous, metabolically versatile and can cause chronic opportunistic infections in immunocompromised patients and in patients with cystic fibrosis (CF) [1]. We performed the systematic assessment of a number of relevant phenotypic characteristics in the context of CF infections, of eleven serial isolates obtained from a CF patient colonized during three and a half years until the patient’s death with the cepacia syndrome [15] These isolates are indistinguishable based on the recA-RFLP and EcoRI ribopattern profiles [17] and belong to the same clonal Based Upon Related Sequence Types (BURST) group [15], consistent with the idea that the CF patient’s lungs can be chronically colonized for years by one or a few lineages of P. aeruginosa and Bcc bacteria [17,18,19,20]. This systematic phenotypic analysis suggested the occurrence of clonal expansion of B. cenocepacia during chronic lung infection presumably as the result of mutations and selective pressures occurring in the CF lung environment, in particular due to host immune defenses, antibiotic therapy and oxygen limitation, as proposed for P. aeruginosa [6,7,9,10,11,19,21]
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
