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Fitness of Isogenic Colony Morphology Variants of Pseudomonas aeruginosa in Murine Airway Infection
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BibTeX
@MISC{Rakhimova_fitnessof,
author = {Elza Rakhimova and Antje Munder and Lutz Wiehlmann and Florian Bredenbruch and Burkhard Tümmler},
title = {Fitness of Isogenic Colony Morphology Variants of Pseudomonas aeruginosa in Murine Airway Infection},
year = {}
}
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Abstract
Chronic lung infections with Pseudomonas aeruginosa are associated with the diversification of the persisting clone into niche specialists and morphotypes, a phenomenon called ‘dissociative behaviour’. To explore the potential of P. aeruginosa to change its morphotype by single step loss-of–function mutagenesis, a signature-tagged mini-Tn5 plasposon library of the cystic fibrosis airway isolate TBCF10839 was screened for colony morphology variants under nine different conditions in vitro. Transposon insertion into 1 % of the genome changed colony morphology into eight discernable morphotypes. Half of the 55 targets encode features of primary or secondary metabolism whereby quinolone production was frequently affected. In the other half the transposon had inserted into genes of the functional categories transport, regulation or motility/ chemotaxis. To mimic dissociative behaviour of isogenic strains in lungs, pools of 25 colony morphology variants were tested for competitive fitness in an acute murine airway infection model. Six of the 55 mutants either grew better or worse in vivo than in vitro, respectively. Metabolic proficiency of the colony morphology variant was a key determinant for survival in murine airways. The most common morphotype of self-destructive autolysis did unexpectedly not impair fitness. Transposon insertions into homologous genes of strain PAO1 did not reproduce the TBCF10839 mutant morphotypes for 16 of 19 examined loci pointing to an important role of the genetic background on colony morphology. Depending on the chosen P. aeruginosa strain, functional genome scans will explore other areas of the evolutionary landscape. Based on our
Keyphrases
pseudomonas aeruginosa murine airway infection colony morphology variant isogenic colony morphology variant transposon insertion colony morphology dissociative behaviour important role signature-tagged mini-tn5 plasposon library homologous gene aeruginosa strain functional category transport murine airway motility chemotaxis isolate tbcf10839 impair fitness different condition evolutionary landscape examined locus isogenic strain competitive fitness quinolone production niche specialist metabolic proficiency cystic fibrosis target encode feature secondary metabolism chronic lung infection functional genome scan tbcf10839 mutant morphotypes discernable morphotypes acute murine airway infection model key determinant strain pao1 self-destructive autolysis genetic background common morphotype single step loss-of function mutagenesis
