scholarly journals Chronic Staphylococcus aureus lung infection correlates with proteogenomic and metabolic adaptations leading to an increased intracellular persistence

2018 ◽  
Author(s):  
Xin Tan ◽  
Mathieu Coureuil ◽  
Elodie Ramond ◽  
Daniel Euphrasie ◽  
Marion Dupuis ◽  
...  
Keyword(s):  
Cystic Fibrosis ◽  
Staphylococcus Aureus ◽  
Molecular Mechanisms ◽  
Expression Profiles ◽  
Lung Infection ◽  
Genetic Modifications ◽  
Protein Expression Profiles ◽  
First Time ◽  
Chronic Lung Infection

AbstractBackgroundChronic lung infection of cystic fibrosis (CF) patients by Staphylococcus aureus is a well-established epidemiological fact. Indeed, S. aureus is the most commonly identified pathogen in the lungs of CF patients. Strikingly the molecular mechanisms underlying S. aureus persistency are not understood.MethodsWe selected pairs of sequential S. aureus isolates from 3 patients with CF and from one patient with non-CF chronic lung disease. We used a combination of genomic, proteomic and metabolomic approaches with functional assays for in-depth characterization of S. aureus long-term persistence.ResultsFor the first time, we show that late S. aureus isolates from CF patients have an increased ability for intracellular survival in CFBE-F508del cells compared to ancestral early isolates. Importantly, the increased ability to persist intracellularly was confirmed for S. aureus isolates within the own patient F508del epithelial cells. An increased ability to form biofilm was also demonstrated.Furthermore, we identified the underlying genetic modifications inducing altered protein expression profiles and notable metabolic changes. These modifications affect several metabolic pathways and virulence regulators that could constitute therapeutic targets.ConclusionsOur results strongly suggest that the intracellular environment might constitute an important niche of persistence and relapse necessitating adapted antibiotic treatments.SummaryS. aureus persists for years in the lungs of patients with cystic fibrosis despite antibiotic therapies. We demonstrate that S. aureus adaptation leads to increased intracellular persistence suggesting a key role for intracellular niche during S. aureus chronic lung infection.

scholarly journals Chronic Staphylococcus aureus Lung Infection Correlates With Proteogenomic and Metabolic Adaptations Leading to an Increased Intracellular Persistence

2019 ◽  
Vol 69 (11) ◽  
pp. 1937-1945 ◽  
Author(s):  
Xin Tan ◽  
Mathieu Coureuil ◽  
Elodie Ramond ◽  
Daniel Euphrasie ◽  
Marion Dupuis ◽  
...  
Keyword(s):  
Staphylococcus Aureus ◽  
Expression Profiles ◽  
Lung Infection ◽  
Bronchial Epithelial ◽  
Metabolic Adaptations ◽  
Genetic Modifications ◽  
Protein Expression Profiles ◽  
Chronic Lung Infection

Abstract Background Chronic lung infection in cystic fibrosis (CF) patients by Staphylococcus aureus is a well-established epidemiological fact. Indeed, S. aureus is the most commonly identified pathogen in the lungs of CF patients. Improving our understanding of the mechanisms associated with the persistence of S. aureus is therefore an important issue. Methods We selected pairs of sequential S. aureus isolates from 3 patients with CF and from 1 patient with non-CF chronic lung disease. We used a combination of genomic, proteomic, and metabolomic approaches with functional assays for in-depth characterization of S. aureus long-term persistence. Results In this study, we show that late S. aureus isolates from CF patients have an increased ability for intracellular survival in CF bronchial epithelial-F508del cells compared to ancestral early isolates. Importantly, the increased ability to persist intracellularly was confirmed for S. aureus isolates within the own-patient F508del epithelial cells. An increased ability to form biofilm was also demonstrated. Furthermore, we identified the underlying genetic modifications that induce altered protein expression profiles and notable metabolic changes. These modifications affect several metabolic pathways and virulence regulators that could constitute therapeutic targets. Conclusions Our results strongly suggest that the intracellular environment might constitute an important niche of persistence and relapse necessitating adapted antibiotic treatments.

Unorthodox long-term aerosolized ampicillin use for methicillin-susceptible Staphylococcus aureus lung infection in a cystic fibrosis patient

2009 ◽  
Vol 44 (5) ◽  
pp. 512-515 ◽  
Author(s):  
Luis Máiz ◽  
Adelaida Lamas ◽  
Ana Fernández-Olmos ◽  
Lucrecia Suárez ◽  
Rafael Cantón
Keyword(s):  
Cystic Fibrosis ◽  
Staphylococcus Aureus ◽  
Cystic Fibrosis Patient ◽  
Lung Infection

scholarly journals Epidemiological significance of genome variations in Pseudomonas aeruginosa causing chronic lung infection in patients with cystic fibrosis

2019 ◽  
Vol 21 (4) ◽  
pp. 340-351
Author(s):  
I.A. Shaginyan ◽  
L.R. Avetisyan ◽  
Marina Yu. Chernukha ◽  
E.A. Siyanova ◽  
E.M. Burmistrov ◽  
...  
Keyword(s):  
Cystic Fibrosis ◽  
Web Application ◽  
Molecular Mechanisms ◽  
Lung Infection ◽  
Population Heterogeneity ◽  
Control Measures ◽  
Diffusion Method ◽  
Pathogen Variability ◽  
Epidemiological Significance ◽  
Chronic Lung Infection

Objective. To present the data on the main mechanism of molecular variation in P. aeruginosa causing chronic lung infection in patients with cystic fibrosis. Materials and Methods. A total of 1800 throat swabs and sputum samples from cystic fibrosis patients were included in the study over the 10-year period. P. aeruginosa isolates were primarily identified by the biochemical method using the API 20NE test strips (bioMerieux, France). Antimicrobial susceptibility testing was performed by disc diffusion method. Genotyping was conducted by RAPD-PCR and MLST. Whole genome sequencing of three typical P. aeruginosa isolates was performed on an Ion PGM Torrent platform with Ion Sequencing Kit and 316v1 chips (Life Technologies Thermo Fisher, US) according to the manufacturer’s protocol. The RAST web application was used for initial annotation. Results. There were three main variants of the pathogen variability found: population heterogeneity, pathogen microevolution, and replacement by another genotype of the same species. The variation of the pathogen’s genome is due to the acquisition of mobile genetic elements (plasmids), mutations in the chromosomal genes responsible for antibiotic resistance, bacterial viability and survival during persistence in a host, and changes in the prophage regions of the pathogen. Conclusions. Epidemiological significance of the molecular mechanisms of pathogen variation is primarily due to the ability of strains to form epidemiologically significant clone. This requires control measures aimed to limit emergence and distribution of such clones to be developed.

scholarly journals Transcriptome-wide gene expression plasticity in Stipa grandis in response to grazing intensity differences

2020 ◽  
Author(s):  
Zhenhua Dang ◽  
Yuanyuan Jia ◽  
Yunyun Tian ◽  
Jiabin Li ◽  
Yanan Zhang ◽  
...  
Keyword(s):  
Gene Expression ◽  
Metabolic Pathways ◽  
Molecular Mechanisms ◽  
Expression Profiles ◽  
Gene Expression Profiles ◽  
Grazing Intensity ◽  
Glycolate Oxidase ◽  
Bisphosphate Carboxylase ◽  
Grazing Intensities

Organisms have evolved effective and distinct adaptive strategies to survive. Stipa grandis is one of the widespread dominant species on the typical steppe of the Inner Mongolian Plateau, and is regarded as a suitable species for studying the effects of grazing in this region. Although phenotypic (morphological and physiological) variations in S. grandis in response to long-term grazing have been identified, the molecular mechanisms underlying adaptations and plastic responses remain largely unknown. Accordingly, we performed a transcriptomic analysis to investigate changes in gene expression of S. grandis under four different grazing intensities. A total of 2,357 differentially expressed genes (DEGs) were identified among the tested grazing intensities, suggesting long-term grazing resulted in gene expression plasticity that affected diverse biological processes and metabolic pathways in S. grandis. DEGs were identified that indicated modulation of Calvin–Benson cycle and photorespiration metabolic pathways. The key gene´expression profiles encoding various proteins (e.g., Ribulose-1,5-bisphosphate carboxylase/oxygenase, fructose-1,6-bisphosphate aldolase, glycolate oxidase etc.) involved in these pathways suggest that they may synergistically respond to grazing to increase the resilience and stress tolerance of S. grandis. Our findings provide scientific clues for improving grassland use and protection, and identify important questions to address in future transcriptome studies.

Chronic Lung Infection Caused by Trichosporon mycotoxinivorans and Trichosporon mucoides in an Immunocompetent Cystic Fibrosis Patient

2016 ◽  
Vol 52 (7) ◽  
pp. 400 ◽  
Author(s):  
Francisco de Borja Martínez Muñiz ◽  
María Martínez Redondo ◽  
Concepción Prados Sánchez ◽  
Julio García Rodríguez
Keyword(s):  
Cystic Fibrosis ◽  
Cystic Fibrosis Patient ◽  
Lung Infection ◽  
Chronic Lung Infection

scholarly journals Influence of Acetylsalicylic Acid Use on Risk and Outcome of Community-Acquired Staphylococcus aureus Bacteremia: A Population-Based Study

2019 ◽  
Vol 6 (9) ◽  
Author(s):  
Jesper Smit ◽  
Michael Dalager-Pedersen ◽  
Kasper Adelborg ◽  
Achim J Kaasch ◽  
Reimar W Thomsen ◽  
...  
Keyword(s):  
Staphylococcus Aureus ◽  
Acetylsalicylic Acid ◽  
Population Based ◽  
Socioeconomic Indicators ◽  
Medical Databases ◽  
Staphylococcus Aureus Bacteremia ◽  
Increased Risk ◽  
First Time ◽  
Population Controls

Abstract Objective To investigate the influence of acetylsalicylic acid (ASA) use on risk and outcome of community-acquired Staphylococcus aureus bacteremia (CA-SAB). Method We used population-based medical databases to identify all patients diagnosed in northern Denmark with first-time CA-SAB and matched population controls from 2000–2011. Categories for ASA users included current users (new or long-term users), former users, and nonusers. The analyses were adjusted for comorbidities, comedication use, and socioeconomic indicators. Results We identified 2638 patients with first-time CA-SAB and 26 379 matched population controls. Compared with nonusers, the adjusted odds ratio (aOR) for CA-SAB was 1.00 (95% confidence interval [CI], 0.88–1.13) for current users, 1.00 (95% CI, 0.86–1.16) for former users, 2.04 (95% CI, 1.42–2.94) for new users, and 0.95 (95% CI, 0.84–1.09) for long-term users. Thirty-day cumulative mortality was 28.0% among current users compared with 21.6% among nonusers, yielding an adjusted hazard rate ratio (aHRR) of 1.02 (95% CI, 0.84–1.25). Compared with nonusers, the aHRR was 1.10 (95% CI, 0.87–1.40) for former users, 0.60 (95% CI, 0.29–1.21) for new users, and 1.06 (95% CI, 0.87–1.31) for long-term users. We observed no difference in the risk or outcome of CA-SAB with increasing ASA dose or by presence of diseases commonly treated with ASA. Conclusions Use of ASA did not seem to influence the risk or outcome of CA-SAB. The apparent increased risk among new users may relate to residual confounding from the circumstances underlying ASA treatment initiation. Our finding of no association remained robust with increasing ASA dose and across multiple patient subsets.

scholarly journals True Microbiota Involved in Chronic Lung Infection of Cystic Fibrosis Patients Found by Culturing and 16S rRNA Gene Analysis

2011 ◽  
Vol 49 (12) ◽  
pp. 4352-4355 ◽  
Author(s):  
V. B. Rudkjobing ◽  
T. R. Thomsen ◽  
M. Alhede ◽  
K. N. Kragh ◽  
P. H. Nielsen ◽  
...  
Keyword(s):  
Cystic Fibrosis ◽  
16S Rrna ◽  
16S Rrna Gene ◽  
Lung Infection ◽  
Gene Analysis ◽  
Rrna Gene ◽  
16S Rrna Gene Analysis ◽  
Chronic Lung Infection

scholarly journals Transcriptomic Analysis of mRNA-lncRNA-miRNA Interactions in Hepatocellular Carcinoma

2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Xia Tang ◽  
Delong Feng ◽  
Min Li ◽  
Jinxue Zhou ◽  
Xiaoyuan Li ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Molecular Mechanisms ◽  
Expression Profiles ◽  
Rna Seq ◽  
Pairwise Interactions ◽  
Micro Rnas ◽  
Non Coding Rnas ◽  
First Time

Abstract Fully elucidating the molecular mechanisms of non-coding RNAs (ncRNAs), including micro RNAs (miRNAs) and long non-coding RNAs (lncRNAs), underlying hepatocarcinogenesis is challenging. We characterized the expression profiles of ncRNAs and constructed a regulatory mRNA-lncRNA-miRNA (MLMI) network based on transcriptome sequencing (RNA-seq) of hepatocellular carcinoma (HCC, n = 9) patients. Of the identified miRNAs (n = 203) and lncRNAs (n = 1,090), we found 16 significantly differentially expressed (DE) miRNAs and three DE lncRNAs. The DE RNAs were highly enriched in 21 functional pathways implicated in HCC (p < 0.05), including p53, MAPK, and NAFLD signaling. Potential pairwise interactions between DE ncRNAs and mRNAs were fully characterized using in silico prediction and experimentally-validated evidence. We for the first time constructed a MLMI network of reciprocal interactions for 16 miRNAs, three lncRNAs, and 253 mRNAs in HCC. The predominant role of MEG3 in the MLMI network was validated by its overexpression in vitro that the expression levels of a proportion of MEG3-targeted miRNAs and mRNAs was changed significantly. Our results suggested that the comprehensive MLMI network synergistically modulated carcinogenesis, and the crosstalk of the network provides a new avenue to accurately describe the molecular mechanisms of hepatocarcinogenesis.

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