Bacterial evolution in PCD and CF patients follows the same mutational steps

TY - JOUR

T1 - Bacterial evolution in PCD and CF patients follows the same mutational steps

AU - Sommer, Lea M

AU - Alanin, Mikkel Christian

AU - Marvig, Rasmus L

AU - Nielsen, Kim Gjerum

AU - Høiby, Niels

AU - von Buchwald, Christian

AU - Molin, Søren

AU - Johansen, Helle Krogh

PY - 2016/6/28

Y1 - 2016/6/28

N2 - Infections with Pseudomonas aeruginosa increase morbidity in primary ciliary dyskinesia (PCD) and cystic fibrosis (CF) patients. Both diseases are associated with a defect of the mucociliary clearance; in PCD caused by non-functional cilia, in CF by changed mucus. Whole genome sequencing of P. aeruginosa isolates from CF patients has shown that persistence of clonal lineages in the airways is facilitated by genetic adaptation. It is unknown whether this also applies to P. aeruginosa airway infections in PCD. We compared within-host evolution of P. aeruginosa in PCD and CF patients. P. aeruginosa isolates from 12 PCD patients were whole genome sequenced and phenotypically characterised. Ten out of 12 PCD patients were infected with persisting clone types. We identified convergent evolution in eight genes, which are also important for persistent infections in CF airways: genes related to antibiotic resistance, quorum sensing, motility, type III secretion and mucoidity. We document phenotypic and genotypic parallelism in the evolution of P. aeruginosa across infected patients with different genetic disorders. The parallel changes and convergent adaptation and evolution may be caused by similar selective forces such as the intensive antibiotic treatment and the inflammatory response, which drive the evolutionary processes.

AB - Infections with Pseudomonas aeruginosa increase morbidity in primary ciliary dyskinesia (PCD) and cystic fibrosis (CF) patients. Both diseases are associated with a defect of the mucociliary clearance; in PCD caused by non-functional cilia, in CF by changed mucus. Whole genome sequencing of P. aeruginosa isolates from CF patients has shown that persistence of clonal lineages in the airways is facilitated by genetic adaptation. It is unknown whether this also applies to P. aeruginosa airway infections in PCD. We compared within-host evolution of P. aeruginosa in PCD and CF patients. P. aeruginosa isolates from 12 PCD patients were whole genome sequenced and phenotypically characterised. Ten out of 12 PCD patients were infected with persisting clone types. We identified convergent evolution in eight genes, which are also important for persistent infections in CF airways: genes related to antibiotic resistance, quorum sensing, motility, type III secretion and mucoidity. We document phenotypic and genotypic parallelism in the evolution of P. aeruginosa across infected patients with different genetic disorders. The parallel changes and convergent adaptation and evolution may be caused by similar selective forces such as the intensive antibiotic treatment and the inflammatory response, which drive the evolutionary processes.

KW - Journal Article

U2 - 10.1038/srep28732

DO - 10.1038/srep28732

M3 - Journal article

C2 - 27349973

SN - 2045-2322

VL - 6

JO - Scientific Reports

JF - Scientific Reports

M1 - 28732

ER -