Investigating the host and bacterial factors in cystic fibrosis that promote persistence of infection in the lung

Smith, Daniel J.

doi:10.14264/uql.2015.854

Cited by 1 publication

(1 citation statement)

References 236 publications

(408 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The iron-responsive small RNAs PrrF1 and PrrF2 (Wang et al, 2012) were upregulated in both PASS4 (11-fold and 19-fold, respectively) and PAO1 (both by 6-fold) (Figure 3). During iron limitation, these small RNAs enable inhibition of genes that encode “non-essential” iron-containing proteins (Smith, 2015). Additionally, PASS4 grown in DNA displayed an increased abundance of iron acquisition proteins including the putative TonB-dependent receptor family protein (PA0781), TonB-dependent siderophore receptor (PA4837), FeoB Fe 2+ transporter (PA4358), FecA ferric citrate receptor (PA3901) and FiuR iron transport protein.…”

Section: Resultsmentioning

confidence: 99%

Catabolism of Nucleic Acids by a Cystic Fibrosis Pseudomonas aeruginosa Isolate: An Adaptive Pathway to Cystic Fibrosis Sputum Environment

et al. 2019

View full text Add to dashboard Cite

Pseudomonas aeruginosa is a major cause of morbidity and mortality in patients with cystic fibrosis (CF). We undertook Biolog Phenotype Microarray testing of P. aeruginosa CF isolates to investigate their catabolic capabilities compared to P. aeruginosa laboratory strains PAO1 and PA14. One strain, PASS4, displayed an unusual phenotype, only showing strong respiration on adenosine and inosine. Further testing indicated that PASS4 could grow on DNA as a sole carbon source, with a higher biomass production than PAO1. This suggested that PASS4 was specifically adapted to metabolize extracellular DNA, a substrate present at high concentrations in the CF lung. Transcriptomic and proteomic profiling of PASS4 and PAO1 when grown with DNA as a sole carbon source identified a set of upregulated genes, including virulence and host-adaptation genes. PASS4 was unable to utilize N -Acetyl- D -glucosamine, and when we selected PASS4 mutants able to grow on this carbon source, they also displayed a gain in ability to catabolize a broad range of other carbon sources. Genome sequencing of the mutants revealed they all contained mutations within the purK gene, encoding a key protein in the de novo purine biosynthesis pathway. This suggested that PASS4 was a purine auxotroph. Growth assays in the presence of 2 mM adenosine and the complementation of PASS4 with an intact purK gene confirmed this conclusion. Purine auxotrophy may represent a viable microbial strategy for adaptation to DNA-rich environments such as the CF lung.

show abstract

Section: Resultsmentioning

confidence: 99%