Competitive survival of clonal serial Pseudomonas aeruginosa isolates from cystic fibrosis airways in human neutrophils
Pia Kuschnerow,
Antje Munder,
Nicole de Buhr,
Matthias Mörgelin,
Adan Chari Jirmo,
Mania Ackermann,
Maren von Köckritz-Blickwede,
Burkhard Tümmler,
Nina Cramer
Affiliations
Pia Kuschnerow
Department of Pediatric Pneumology, Allergology and Neonatology, Hannover Medical School, Carl-Neuberg-Str. 1, 30625 Hannover, Germany; German Center for Infection Research (DZIF), 30625 Hannover, Germany
Antje Munder
Department of Pediatric Pneumology, Allergology and Neonatology, Hannover Medical School, Carl-Neuberg-Str. 1, 30625 Hannover, Germany; Biomedical Research in Endstage and Obstructive Lung Disease Hannover (BREATH), Member of the German Center for Lung Research (DZL), 30625 Hannover, Germany
Nicole de Buhr
Department of Biochemistry, University of Veterinary Medicine Hannover, Bünteweg 2, 30559 Hannover, Germany; Research Center for Emerging Infections and Zoonoses (RIZ), University of Veterinary Medicine Hannover, 30559 Hannover, Germany
Matthias Mörgelin
Colzyx AB, Medicon Village, Scheeletorget 1, 22363 Lund, Sweden
Adan Chari Jirmo
Department of Pediatric Pneumology, Allergology and Neonatology, Hannover Medical School, Carl-Neuberg-Str. 1, 30625 Hannover, Germany; Biomedical Research in Endstage and Obstructive Lung Disease Hannover (BREATH), Member of the German Center for Lung Research (DZL), 30625 Hannover, Germany
Mania Ackermann
Department of Pediatric Pneumology, Allergology and Neonatology, Hannover Medical School, Carl-Neuberg-Str. 1, 30625 Hannover, Germany
Maren von Köckritz-Blickwede
Department of Biochemistry, University of Veterinary Medicine Hannover, Bünteweg 2, 30559 Hannover, Germany; Research Center for Emerging Infections and Zoonoses (RIZ), University of Veterinary Medicine Hannover, 30559 Hannover, Germany
Burkhard Tümmler
Department of Pediatric Pneumology, Allergology and Neonatology, Hannover Medical School, Carl-Neuberg-Str. 1, 30625 Hannover, Germany; Biomedical Research in Endstage and Obstructive Lung Disease Hannover (BREATH), Member of the German Center for Lung Research (DZL), 30625 Hannover, Germany
Nina Cramer
Department of Pediatric Pneumology, Allergology and Neonatology, Hannover Medical School, Carl-Neuberg-Str. 1, 30625 Hannover, Germany; German Center for Infection Research (DZIF), 30625 Hannover, Germany; Corresponding author
Summary: Chronic airway infections with Pseudomonas aeruginosa are the major co-morbidity in most people with cystic fibrosis (CF) sustained by neutrophils as the major drivers of lung inflammation, damage, and remodeling. Phagocytosis assays were performed with clonal consortia of longitudinal P. aeruginosa airway isolates collected from people with CF since the onset of lung colonization until patient’s death or replacement by another clone. The extra- and intracellular abundance of individual strains was assessed by deep amplicon sequencing of strain-specific single nucleotide variants in the bacterial genome. The varied microevolution of the accessory genome of the P. aeruginosa clones during mild and severe courses of infection corresponded with a differential persistence of clonal progeny in the neutrophil phagosome. By simultaneously exposing the ancestor and its progeny to the same habitat, the study recapitulated the time lapse of the temporal change of the fitness of the clone to survive in neutrophils.
