The high persister phenotype of Pseudomonas aeruginosa is associated with increased fitness and persistence in cystic fibrosis airways

Biljana Mojsoska, David R. Cameron, Jennifer A. Bartell, Janus A.J. Haagensen, Lea M. Sommer, Kim Lewis, Søren Molin, Helle Krogh Johansen

Research output: Working paperResearch

Abstract

Pseudomonas aeruginosa (P.a) is responsible for the majority of chronic lung infections in patients suffering from cystic fibrosis (CF) [1]. Despite intensive treatment with antibiotics from the first discovery of this bacterium in the patient lungs, and despite the fact that only few cases of antibiotic resistance are observed the first many years, these bacteria persist and adapt, and eventually develop incurable chronic airway infections in most patients. 'Persister bacteria' are susceptible cells that survive antibiotic treatment and can resume growth when antibiotics are no longer present, resulting in antibiotic tolerance. Persister bacteria increase the phenotypic heterogeneity within bacterial population, challenging our understanding of how these persisters are formed and how they persist within the host. This paper focuses on the significance of treatment failure associated with the high persister (Hip) phenotype among P.a. clinical isolates. The clinical isolates have been screened using in vitro persister assay for exhibiting with varying persister phenotypes, high (Hip) and low (Lop). It has been proposed the initiation of recurrent infections, is governed by the subpopulation of persister cells. Understadning oft he dynamicity of the persister phnotype among clinical isolates and their contribution to the recurance of infections and failure of eradication. Chronic P. aeruginosa infection in patients with cystic fibrosis presents an interesting paradox; antibiotics fail to fully eradicate antibiotic susceptible bacteria. We hypothesized based on our previous findings that treatment failure may be due to the presence of high persister (hip) mutants that have enhanced antibiotic tolerance [2]. More than 75 % of the patients used in this study are chronically infected with Pseudomonas aeruginosa according to the Copenhagen definitions of chronicity [3]. Many of the isolates failed to grow in any replicate (XXX) and the majority of isolates were defined as low persisters (74.3 %). The remaining 25.7 % of isolates were hip mutants and of these 40 % were clinically defined as ciprofloxacin susceptible. The genetics analysis reveal a large number of genes with different functionalities to be enriched in the Hip population of isolates. One can speculate that this genetic heterogeneity enables survival of the various hip mutants under a wide range of harmful conditions.
Original languageEnglish
PublisherCold Spring Harbor Laboratory Press
DOIs
Publication statusPublished - 27 Feb 2019

Cite this

Mojsoska, B., Cameron, D. R., Bartell, J. A., Haagensen, J. A. J., Sommer, L. M., Lewis, K., ... Johansen, H. K. (2019). The high persister phenotype of Pseudomonas aeruginosa is associated with increased fitness and persistence in cystic fibrosis airways. Cold Spring Harbor Laboratory Press. https://doi.org/10.1101/561589, https://doi.org/10.1101/561589