Transcriptomic analysis of longitudinalBurkholderia pseudomalleiinfecting the cystic fibrosis lung
| Autor: | Scott C. Bell, Timothy J. Kidd, Erin P. Price, Bart J. Currie, Linda T. Viberg, Derek S. Sarovich |
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| Rok vydání: | 2017 |
| Předmět: |
Male
0301 basic medicine Pathology medicine.medical_specialty antibiotic resistance Burkholderia pseudomallei Melioidosis Cystic Fibrosis medicine.drug_class 030106 microbiology Antibiotics Biology Cystic fibrosis Microbiology Transcriptome 03 medical and health sciences pathoadaptation Antibiotic resistance Text mining Bacterial Proteins evolution Gene expression medicine Humans Gene Pathogen 030304 developmental biology bacterial transcriptomics 0303 health sciences convergence Lung 030306 microbiology business.industry Gene Expression Profiling Gene Expression Regulation Bacterial General Medicine biology.organism_classification medicine.disease 3. Good health 030104 developmental biology medicine.anatomical_structure Systems Microbiology: Transcriptomics Proteomics Networks RNA-seq business Research Article |
| Zdroj: | Microbial Genomics |
| DOI: | 10.1101/229823 |
| Popis: | The melioidosis bacterium,Burkholderia pseudomallei, is increasingly being recognized as a pathogen in patients with cystic fibrosis (CF). We have recently catalogued genome-wide variation of paired, isogenicB. pseudomalleiisolates from seven Australasian CF cases, which were collected between four and 55 months apart. Here, we extend this investigation by documenting the transcriptomic changes inB. pseudomalleiin five cases. Following growth in an artificial CF sputum medium, four of the five paired isolates exhibited significant differential gene expression (DE) that affected between 32 and 792 genes. The greatest number of DE events was observed between patient CF9 strains, consistent with the hypermutator status of the latter strain, which is deficient in the DNA mismatch repair protein MutS. Two patient isolates harbored duplications that concomitantly increased expression of the β-lactamase genepenA, and a 35kb deletion in another abolished expression of 29 genes. Convergent expression profiles in the chronically-adapted isolates identified two significantly downregulated and 17 significantly upregulated loci, including the antibiotic resistance-nodulation-division (RND) efflux pump BpeEF-OprC, the quorum-sensinghhqABCDEoperon, and a cyanide- and pyocyanin-insensitive cytochromebdquinol oxidase. These convergent pathoadaptations lead to increased expression of pathways that may suppress competing bacterial and fungal pathogens and that enhance survival in oxygen-restricted environments, the latter of which may render conventional antibiotics less effectivein vivo. Treating chronically-adaptedB. pseudomalleiinfections with antibiotics designed to target anaerobic infections, such as the nitroimidazole class of antibiotics, may significantly improve pathogen eradication attempts by exploiting this Achilles heel. |
| Databáze: | OpenAIRE |
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