Dataset Information

Great phenotypic and genetic variation among successive chronic Pseudomonas aeruginosa from a cystic fibrosis patient.

ABSTRACT: BACKGROUND/OBJECTIVES:Different adapted Pseudomonas aeruginosa morphotypes are found during chronic infections. Relevant biological determinants in P. aeruginosa successively isolated from a cystic fibrosis (CF) patient were analyzed in this work to gain insight into P. aeruginosa heterogeneity during chronic infection. METHODS:Seventeen P. aeruginosa isolates collected from a patient over a 3 year period were included, 5 small colony variants (SCV) and 12 mucoids. The following analyses were performed: Pulsed-Field-Gel-Electrophoresis (PFGE)/Multilocus- sequence-typing (MLST)/serotype, antimicrobial susceptibility, growth curves, capacity to form biofilm, pigment production, elastase activity, motility; presence/expression of virulence/quorum sensing genes, and identification of resistance mechanisms. RESULTS:All isolates had closely related PFGE patterns and belonged to ST412. Important phenotypic and genotypic differences were found. SCVs were more resistant to antimicrobials than mucoid isolates. AmpC hyperproduction and efflux pump activity were detected. Seven isolates contained two integrons and nine isolates only one integron. All SCVs showed the same OprD profile, while three different profiles were identified among mucoids. No amino acid changes were found in MutL and MutS. All isolates were slow-growing, generally produced high biofilm, had reduced their toxin expression and their quorum sensing, and showed low motility. Nevertheless, statistically significant differences were found among SCV and mucoid isolates. SCVs grew faster, presented higher biofilm formation and flicA expression; but produced less pyorubin and pyocyanin, showed lower elastase activity and rhlR, algD, and lasB expression than mucoid isolates. CONCLUSION:These results help to understand the molecular behavior of chronic P. aeruginosa isolates in CF patients.

SUBMITTER: Lozano C

PROVIDER: S-EPMC6136817 | biostudies-literature | 2018

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Great phenotypic and genetic variation among successive chronic Pseudomonas aeruginosa from a cystic fibrosis patient.

Lozano Carmen C Azcona-Gutiérrez José Manuel JM Van Bambeke Françoise F Sáenz Yolanda Y

PloS one 20180913 9

<h4>Background/objectives</h4>Different adapted Pseudomonas aeruginosa morphotypes are found during chronic infections. Relevant biological determinants in P. aeruginosa successively isolated from a cystic fibrosis (CF) patient were analyzed in this work to gain insight into P. aeruginosa heterogeneity during chronic infection.<h4>Methods</h4>Seventeen P. aeruginosa isolates collected from a patient over a 3 year period were included, 5 small colony variants (SCV) and 12 mucoids. The following a ...[more]

PMID: 30212579

Similar Datasets

Project description:Pseudomonas aeruginosa is an opportunistic pathogen which is evolving resistance to many currently used antibiotics. While much research has been devoted to the roles of pathogenic P. aeruginosa in cystic fibrosis (CF) patients, less is known of its ecological properties. P. aeruginosa dominates the lungs during chronic infection in CF patients, yet its abundance in some environments is less than that of other diverse groups of pseudomonads. Here, we sought to determine if clinical isolates of P. aeruginosa are vulnerable to environmental pseudomonads that dominate soil and water habitats in one-to-one competitions which may provide a source of inhibitory factors. We isolated a total of 330 pseudomonads from diverse habitats of soil and freshwater ecosystems and competed these strains against one another to determine their capacity for antagonistic activity. Over 900 individual inhibitory events were observed. Extending the analysis to P. aeruginosa isolates revealed that clinical isolates, including ones with increased alginate production, were susceptible to competition by multiple environmental strains. We performed transposon mutagenesis on one isolate and identified an ?14.8-kb locus involved in antagonistic activity. Only two other environmental isolates were observed to carry the locus, suggesting the presence of additional unique compounds or interactions among other isolates involved in outcompeting P. aeruginosa This collection of strains represents a source of compounds that are active against multiple pathogenic strains. With the evolution of resistance of P. aeruginosa to currently used antibiotics, these environmental strains provide opportunities for novel compound discovery against drug-resistant clinical strains.ImportanceWe demonstrate that clinical CF-derived isolates of P. aeruginosa are susceptible to competition in the presence of environmental pseudomonads. We observed that many diverse environmental strains exhibited varied antagonistic profiles against a panel of clinical P. aeruginosa isolates, suggesting the presence of distinct mechanisms of inhibition among these ecological strains. Understanding the properties of these antagonistic events offers the potential for discoveries of antimicrobial compounds or metabolic pathways important to the development of novel treatments for P. aeruginosa infections.

Project description:RationaleThe effectiveness and safety of aztreonam lysine for inhalation (AZLI) in patients with cystic fibrosis (CF) on maintenance treatment for Pseudomonas aeruginosa (PA) airway infection was evaluated in this randomized, double-blind, placebo-controlled study.ObjectivesTo evaluate the safety and efficacy of inhaled aztreonam lysine in controlling PA infection in patients with CF.MethodsAfter randomization and a 28-day course of tobramycin inhalation solution (TIS), patients (n = 211; > or =6 yr; > or =3 TIS courses within previous year; FEV(1) > or = 25% and < or =75% predicted values) were treated with 75 mg AZLI or placebo, twice or three times daily for 28 days, then monitored for 56 days. The primary efficacy endpoint was time to need for additional inhaled or intravenous antipseudomonal antibiotics. Secondary endpoints included changes in respiratory symptoms (CF Questionnaire-Revised [CFQ-R] Respiratory Scale), pulmonary function (FEV(1)), and sputum PA density. Adverse events and minimum inhibitory concentrations of aztreonam for PA were monitored.Measurements and main resultsAZLI treatment increased median time to need for additional antipseudomonal antibiotics for symptoms of pulmonary exacerbation by 21 days, compared with placebo (AZLI, 92 d; placebo, 71 d; P = 0.007). AZLI improved mean CFQ-R respiratory scores (5.01 points, P = 0.02), FEV(1) (6.3%, P = 0.001), and sputum PA density (-0.66 log(10) cfu/g, P = 0.006) compared with placebo; no AZLI dose-response was observed. Adverse events reported for AZLI and placebo were comparable and consistent with CF lung disease. Susceptibility of PA to aztreonam at baseline and end of therapy were similar.ConclusionsAZLI was effective in patients with CF using frequent TIS therapy. AZLI delayed time to need for inhaled or intravenous antipseudomonal antibiotics, improved respiratory symptoms and pulmonary function, and was well tolerated. Clinical trial registered with www.clinicaltrials.gov (NCT 00104520).

Project description:RationalePseudomonas aeruginosa, the predominant cause of chronic airway infections of patients with cystic fibrosis, exhibits extensive phenotypic diversity among isolates within and between sputum samples, but little is known about the underlying genetic diversity.ObjectivesTo characterize the population genetic structure of transmissible P. aeruginosa Liverpool Epidemic Strain in chronic infections of nine patients with cystic fibrosis, and infer evolutionary processes associated with adaptation to the cystic fibrosis lung.MethodsWe performed whole-genome sequencing of P. aeruginosa isolates and pooled populations and used comparative analyses of genome sequences including phylogenetic reconstructions and resolution of population structure from genome-wide allele frequencies.Measurements and main resultsGenome sequences were obtained for 360 isolates from nine patients. Phylogenetic reconstruction of the ancestry of 40 individually sequenced isolates from one patient sputum sample revealed the coexistence of two genetically diverged, recombining lineages exchanging potentially adaptive mutations. Analysis of population samples for eight additional patients indicated coexisting lineages in six cases. Reconstruction of the ancestry of individually sequenced isolates from all patients indicated smaller genetic distances between than within patients in most cases.ConclusionsOur population-level analysis demonstrates that coexistence of distinct lineages of P. aeruginosa Liverpool Epidemic Strain within individuals is common. In several cases, coexisting lineages may have been present in the infecting inoculum or assembled through multiple transmissions. Divergent lineages can share mutations via homologous recombination, potentially aiding adaptation to the airway during chronic infection. The genetic diversity of this transmissible strain within infections, revealed by high-resolution genomics, has implications for patient segregation and therapeutic strategies.

Dataset Information

Great phenotypic and genetic variation among successive chronic Pseudomonas aeruginosa from a cystic fibrosis patient.

Publications

Great phenotypic and genetic variation among successive chronic Pseudomonas aeruginosa from a cystic fibrosis patient.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure