scholarly journals Antimicrobial susceptibility and genotypification of Pseudomonas aeruginosa from cystic fibrosis patients and other diseases in Cartagena (Colombia)

2014 ◽  
Vol 30 (2) ◽  
pp. 104-120
Author(s):  
Javier Baena ◽  
◽  
Claudio Gomez ◽  
Doris Gomez ◽  
◽  
...  
Keyword(s):  
Cystic Fibrosis ◽  
Pseudomonas Aeruginosa ◽  
Antimicrobial Susceptibility

scholarly journals Heterogeneous Antimicrobial Susceptibility Characteristics inPseudomonas aeruginosaIsolates from Cystic Fibrosis Patients

mSphere ◽  
2018 ◽  
Vol 3 (2) ◽  
Author(s):  
Xuan Qin ◽  
Chuan Zhou ◽  
Danielle M. Zerr ◽  
Amanda Adler ◽  
Amin Addetia ◽  
...  
Keyword(s):  
Cystic Fibrosis ◽  
Pseudomonas Aeruginosa ◽  
Antimicrobial Susceptibility ◽  
Antimicrobial Agents ◽  
Genomic Sequence ◽  
Sequence Data ◽  
Parental Origin ◽  
Adaptive Mutations ◽  
Wide Range ◽  
Susceptibility Patterns

ABSTRACTClinical isolates ofPseudomonas aeruginosafrom patients with cystic fibrosis (CF) are known to differ from those associated with non-CF hosts by colony morphology, drug susceptibility patterns, and genomic hypermutability.Pseudomonas aeruginosaisolates from CF patients have long been recognized for their overall reduced rate of antimicrobial susceptibility, but their intraclonal MIC heterogeneity has long been overlooked. Using two distinct cohorts of clinical strains (n= 224 from 56 CF patients,n= 130 from 68 non-CF patients) isolated in 2013, we demonstrated profound Etest MIC heterogeneity in CFP. aeruginosaisolates in comparison to non-CFP. aeruginosaisolates. On the basis of whole-genome sequencing of 19 CFP. aeruginosaisolates from 9 patients with heterogeneous MICs, the core genome phylogenetic tree confirmed the within-patient CFP. aeruginosaclonal lineage along with considerable coding sequence variability. No extrachromosomal DNA elements or previously characterized antibiotic resistance mutations could account for the wide divergence in antimicrobial MICs betweenP. aeruginosacoisolates, though many heterogeneous mutations in efflux and porin genes and their regulators were present. A unique OprD sequence was conserved among the majority of isolates of CFP. aeruginosaanalyzed, suggesting a pseudomonal response to selective pressure that is common to the isolates. Genomic sequence data also suggested that CF pseudomonal hypermutability was not entirely due to mutations inmutL,mutS, anduvr. We conclude that the net effect of hundreds of adaptive mutations, both shared between clonally related isolate pairs and unshared, accounts for their highly heterogeneous MIC variances. We hypothesize that this heterogeneity is indicative of the pseudomonal syntrophic-like lifestyle under conditions of being “locked” inside a host focal airway environment for prolonged periods.IMPORTANCEPatients with cystic fibrosis endure “chronic focal infections” with a variety of microorganisms. One microorganism,Pseudomonas aeruginosa, adapts to the host and develops resistance to a wide range of antimicrobials. Interestingly, as the infection progresses, multiple isogenic strains ofP. aeruginosaemerge and coexist within the airways of these patients. Despite a common parental origin, the multiple strains ofP. aeruginosadevelop vastly different susceptibility patterns to actively used antimicrobial agents—a phenomenon we define as “heterogeneous MICs.” By sequencing pairs ofP. aeruginosaisolates displaying heterogeneous MICs, we observed widespread isogenic gene lesions in drug transporters, DNA mismatch repair machinery, and many other structural or cellular functions. Coupled with the heterogeneous MICs, these genetic lesions demonstrated a symbiotic response to host selection and suggested evolution of a multicellular syntrophic bacterial lifestyle. Current laboratory standard interpretive criteria do not address the emergence of heterogeneous growth and susceptibilitiesin vitrowith treatment implications.

scholarly journals Temperate Bacteriophages from ChronicPseudomonas aeruginosaLung Infections Show Disease-Specific Changes in Host Range and Modulate Antimicrobial Susceptibility

mSystems ◽  
2019 ◽  
Vol 4 (4) ◽  
Author(s):  
Mohammad A. Tariq ◽  
Francesca L. C. Everest ◽  
Lauren A. Cowley ◽  
Rosanna Wright ◽  
Giles S. Holt ◽  
...  
Keyword(s):  
Cystic Fibrosis ◽  
Pseudomonas Aeruginosa ◽  
Antimicrobial Susceptibility ◽  
Advanced Disease ◽  
Temperate Phage ◽  
Phage Infection ◽  
Phage Lysate ◽  
Content Type ◽  
Diverse Communities ◽  
Disease Specific

ABSTRACTTemperate bacteriophages are a common feature ofPseudomonas aeruginosagenomes, but their role in chronic lung infections is poorly understood. This study was designed to identify the diverse communities of mobileP. aeruginosaphages by employing novel metagenomic methods, to determine cross infectivity, and to demonstrate the influence of phage infection on antimicrobial susceptibility. Mixed temperate phage populations were chemically mobilized from individualP. aeruginosa, isolated from patients with cystic fibrosis (CF) or bronchiectasis (BR). The infectivity phenotype of each temperate phage lysate was evaluated by performing a cross-infection screen against all bacterial isolates and tested for associations with clinical variables. We utilized metagenomic sequencing data generated for each phage lysate and developed a novel bioinformatic approach allowing resolution of individual temperate phage genomes. Finally, we used a subset of the temperate phages to infectP. aeruginosaPAO1 and tested the resulting lysogens for their susceptibility to antibiotics. Here, we resolved 105 temperate phage genomes from 94 lysates that phylogenetically clustered into 8 groups. We observed disease-specific phage infectivity profiles and found that phages induced from bacteria isolated from more advanced disease infected broader ranges ofP. aeruginosaisolates. Importantly, when infecting PAO1in vitrowith 20 different phages, 8 influenced antimicrobial susceptibility. This study shows thatP. aeruginosaisolated from CF and BR patients harbors diverse communities of inducible phages, with hierarchical infectivity profiles that relate to the progression of the disease. Temperate phage infection altered the antimicrobial susceptibility of PAO1 at subinhibitory concentrations of antibiotics, suggesting they may be precursory to antimicrobial resistance.IMPORTANCEPseudomonas aeruginosais a key opportunistic respiratory pathogen in patients with cystic fibrosis and non-cystic fibrosis bronchiectasis. The genomes of these pathogens are enriched with mobile genetic elements including diverse temperate phages. While the temperate phages of the Liverpool epidemic strain have been shown to be active in the human lung and enhance fitness in a rat lung infection model, little is known about their mobilization more broadly acrossP. aeruginosain chronic respiratory infection. Using a novel metagenomic approach, we identified eight groups of temperate phages that were mobilized from 94 clinicalP. aeruginosaisolates. Temperate phages fromP. aeruginosaisolated from more advanced disease showed high infectivity rates across a wide range ofP. aeruginosagenotypes. Furthermore, we showed that multiple phages altered the susceptibility of PAO1 to antibiotics at subinhibitory concentrations.

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