Genotypic Diversity within a Single Pseudomonas aeruginosa Strain Commonly Shared by Australian Patients with Cystic Fibrosis

Tai, Anna; Bell, Scott C.; Kidd, Timothy J.; Trembizki, Ella; Buckley, Cameron; Ramsay, Kay A.; David, Michael Z.; Wainwright, Claire; Grimwood, Keith; Whiley, David M.

doi:10.1371/journal.pone.0144022

Cited by 18 publications

(36 citation statements)

References 39 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Due to the different conditions present in different areas of the respiratory tract, many variants of the same infecting strain may exist and heterogeneity within one population is common in the CF lung [111–113]. The heterogeneity manifests both in terms of genetic and physiological diversity and spatial distributions in the airways.…”

Section: Discussionmentioning

confidence: 99%

Cystic fibrosis lung environment and Pseudomonas aeruginosa infection

et al. 2016

View full text Add to dashboard Cite

BackgroundThe airways of patients with cystic fibrosis (CF) are highly complex, subject to various environmental conditions as well as a distinct microbiota. Pseudomonas aeruginosa is recognized as one of the most important pulmonary pathogens and the predominant cause of morbidity and mortality in CF. A multifarious interplay between the host, pathogens, microbiota, and the environment shapes the course of the disease. There have been several excellent reviews detailing CF pathology, Pseudomonas and the role of environment in CF but only a few reviews connect these entities with regards to influence on the overall course of the disease. A holistic understanding of contributing factors is pertinent to inform new research and therapeutics.DiscussionIn this article, we discuss the deterministic alterations in lung physiology as a result of CF. We also revisit the impact of those changes on the microbiota, with special emphasis on P. aeruginosa and the influence of other non-genetic factors on CF. Substantial past and current research on various genetic and non-genetic aspects of cystic fibrosis has been reviewed to assess the effect of different factors on CF pulmonary infection. A thorough review of contributing factors in CF and the alterations in lung physiology indicate that CF lung infection is multi-factorial with no isolated cause that should be solely targeted to control disease progression. A combinatorial approach may be required to ensure better disease outcomes.ConclusionCF lung infection is a complex disease and requires a broad multidisciplinary approach to improve CF disease outcomes. A holistic understanding of the underlying mechanisms and non-genetic contributing factors in CF is central to development of new and targeted therapeutic strategies.

show abstract

Section: Discussionmentioning

confidence: 99%

Cystic fibrosis lung environment and Pseudomonas aeruginosa infection

et al. 2016

View full text Add to dashboard Cite

show abstract

“…Several studies on P. aeruginosa strains isolated from CF sputum samples, found significant genomic changes in lasR, including truncation, deletion, frame shifts and SNPs, with many resulting in a loss of function (30,39,40,49,69). Although there can be a high percentage of lasR-deficient isolates collected from patients, studies have also shown differential frequencies of functional and intact lasR alleles within patients (13,70). Considering the importance of lasR-dependent social interactions for the fitness of P. aeruginosa, mutation-frequency of lasR within populations of P. aeruginosa could significantly impact on QS-dependent phenotypes and fitness at the population level (71)(72)(73).…”

Section: Discussionmentioning

confidence: 99%

Allelic polymorphism shapes community function in evolving Pseudomonas aeruginosa populations

Azimi

Roberts

Peng

et al. 2019

Preprint

View full text Add to dashboard Cite

AbstractPseudomonas aeruginosa is an opportunistic pathogen that chronically infects the lungs of individuals with cystic fibrosis (CF) by forming antibiotic resistant biofilms. Emergence of phenotypically diverse isolates within CF P. aeruginosa populations has previously been reported, however, the impact of heterogeneity on social behaviors and community function is poorly understood. Here we describe how this heterogeneity impacts on behavioral traits by evolving the strain PAO1 in biofilms grown in a synthetic sputum medium for 50 days. We measured social trait production and antibiotic tolerance and used a metagenomic approach to analyze and assess genomic changes over the duration of the evolution experiment. We found that (i) evolutionary trajectories were reproducible in independently evolving populations; (ii) over 60% of genomic diversity occurred within the first 10 days of selection. We then focused on quorum sensing (QS), a well-studied P. aeruginosa trait that is commonly mutated in strains isolated from CF lungs. We found that at the population level (i) evolution in sputum medium selected for decreased production of QS and QS-dependent traits; (ii) there was a significant correlation between lasR mutant frequency, the loss of protease and the 3O-C12-HSL signal, and an increase in resistance to clinically relevant β-lactam antibiotics, despite no previous antibiotic exposure. Overall, our findings provide insights into the effect of allelic polymorphism on community functions in diverse P. aeruginosa populations. Further, we demonstrate that P. aeruginosa population and evolutionary dynamics can impact on traits important for virulence and can lead to increased tolerance to β-lactam antibiotics.

show abstract

“…AUST-02 is a prevalent shared strain in CF centres around Australia and is the dominant strain in Queensland infecting approximately 40% of patients infected with P. aeruginosa [10, 14, 15]. A recent surveillance study also described the detection of an AUST-02 strain sub-type in approximately 5% of patients attending a single CF treatment centre in Brisbane (Queensland) [16]. This sub-type could be distinguished from all other AUST-02 strains by a unique mexZ ( mexZ-3, M3) and lasR ( lasR -7, L7) genotype and therefore, was designated M3L7 [16].…”

Section: Introductionmentioning

confidence: 99%

“…A recent surveillance study also described the detection of an AUST-02 strain sub-type in approximately 5% of patients attending a single CF treatment centre in Brisbane (Queensland) [16]. This sub-type could be distinguished from all other AUST-02 strains by a unique mexZ ( mexZ-3, M3) and lasR ( lasR -7, L7) genotype and therefore, was designated M3L7 [16]. The M3L7 sub-type is of particular importance given that, compared to other AUST-02 and P. aeruginosa strains, it is associated with enhanced antibiotic resistance and poorer clinical outcomes (e.g.…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Whole genome sequencing reveals the emergence of aPseudomonas aeruginosashared strain sub-lineage among patients treated within a single cystic fibrosis centre

Wee

Tai

Sherrard

et al. 2018

Preprint

View full text Add to dashboard Cite

BackgroundChronic lung infections by Pseudomonas aeruginosa are a significant cause of morbidity and mortality in people with cystic fibrosis (CF). Shared P. aeruginosa strains, that can be transmitted between patients, are of concern and in Australia the AUST-02 shared strain is predominant in individuals attending CF centres in Queensland and Western Australia. M3L7 is a multidrug resistant sub-type of AUST-02 that was recently identified in a Queensland CF centre and was shown to be associated with poorer clinical outcomes. The main aim of this study was to resolve the relationship of the emergent M3L7 sub-type within the AUST-02 group of strains using whole genome sequencing.ResultsA whole-genome core phylogeny of 63 isolates indicated that M3L7 is a monophyletic sub-lineage within the context of the broader AUST-02 group. Relatively short branch lengths connected all of the M3L7 isolates. A phylogeny based on nucleotide polymorphisms present across the genome showed that the chronological estimation of the most recent common ancestor was around 2001 (± 3 years). SNP differences between sequential M3L7 isolates collected 3-4 years apart from five patients suggested both continuous infection of the same strain and cross-infection of some M3L7 variants between patients. The majority of polymorphisms that were characteristic of M3L7 (i.e. acquired after divergence from all other AUST-02 isolates sequenced) were found to produce non-synonymous mutations in virulence and antibiotic resistance genes.ConclusionsM3L7 has recently diverged from a common ancestor indicating descent from a single carrier at a CF treatment centre in Australia. Both adaptation to the lung and transmission of M3L7 between adults attending this centre may have contributed to its rapid dissemination. The study emphasises the importance of clinical management in controlling the emergence of shared strains in CF.

show abstract

Genotypic Diversity within a Single Pseudomonas aeruginosa Strain Commonly Shared by Australian Patients with Cystic Fibrosis

Cited by 18 publications

References 39 publications

Cystic fibrosis lung environment and Pseudomonas aeruginosa infection

Cystic fibrosis lung environment and Pseudomonas aeruginosa infection

Allelic polymorphism shapes community function in evolving Pseudomonas aeruginosa populations

Whole genome sequencing reveals the emergence of aPseudomonas aeruginosashared strain sub-lineage among patients treated within a single cystic fibrosis centre

Contact Info

Product

Resources

About