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

doi:10.1016/j.isci.2023.106475

Competitive survival of clonal serial Pseudomonas aeruginosa isolates from cystic fibrosis airways in human neutrophils

iScience. 2023 Mar 24;26(4):106475. doi: 10.1016/j.isci.2023.106475. eCollection 2023 Apr 21.

Authors

Pia Kuschnerow^{1

2}, Antje Munder^{1

3}, Nicole de Buhr^{4

5}, Matthias Mörgelin⁶, Adan Chari Jirmo^{1

3}, Mania Ackermann¹, Maren von Köckritz-Blickwede^{4

5}, Burkhard Tümmler^{1

3}, Nina Cramer^{1

2}

Affiliations

¹ Department of Pediatric Pneumology, Allergology and Neonatology, Hannover Medical School, Carl-Neuberg-Str. 1, 30625 Hannover, Germany.
² German Center for Infection Research (DZIF), 30625 Hannover, Germany.
³ Biomedical Research in Endstage and Obstructive Lung Disease Hannover (BREATH), Member of the German Center for Lung Research (DZL), 30625 Hannover, Germany.
⁴ Department of Biochemistry, University of Veterinary Medicine Hannover, Bünteweg 2, 30559 Hannover, Germany.
⁵ Research Center for Emerging Infections and Zoonoses (RIZ), University of Veterinary Medicine Hannover, 30559 Hannover, Germany.
⁶ Colzyx AB, Medicon Village, Scheeletorget 1, 22363 Lund, Sweden.

Abstract

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.

Keywords: Immunology; Microbiology; Respiratory medicine.