ArticlePloS one2017
Cysteamine-mediated clearance of antibiotic-resistant pathogens in human cystic fibrosis macrophages.
Article in PloS one, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers, 1 of them a synthesis that pooled it.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
22 citing papers in PubMed, 1 synthesis or guideline pooled it, 33 citations in OpenAlex.
- Guidelines for the use and interpretation of assays for monitoring autophagy (4th edition)Autophagy · 2021Guideline
- Oral cysteamine as an adjunct treatment in cystic fibrosis pulmonary exacerbations: An exploratory randomized clinical trial.PloS one · 2020Trial
- ENaC contributes to macrophage dysfunction in cystic fibrosis.American journal of physiology. Lung cellular and molecular physiology · 2025Article
- Cystic fibrosis macrophage function and clinical outcomes after elexacaftor/tezacaftor/ivacaftor.The European respiratory journal · 2023Article
- The STING/TBK1/IRF3/IFN type I pathway is defective in cystic fibrosis.Frontiers in immunology · 2023Article
- Emerging Concepts in Defective Macrophage Phagocytosis in Cystic Fibrosis.International journal of molecular sciences · 2022Review
- Inhibition of XPO1 Sensitizes Small Cell Lung Cancer to First- and Second-Line Chemotherapy.Cancer research · 2022Article
- Sweat metabolomics before and after intravenous antibiotics for pulmonary exacerbation in people with cystic fibrosis.Respiratory medicine · 2022Article
- Neutrophil Elastase Triggers the Release of Macrophage Extracellular Traps: Relevance to Cystic Fibrosis.American journal of respiratory cell and molecular biology · 2022Article
- Prognosis-Based Early Intervention Strategies to Resolve Exacerbation and Progressive Lung Function Decline in Cystic Fibrosis.Journal of personalized medicine · 2021Article
- A SNARE protein Syntaxin 17 captures CFTR to potentiate autophagosomal clearance under stress.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2021Article
- Cysteamine Inhibits Glycine Utilisation and Disrupts Virulence inFrontiers in cellular and infection microbiology · 2021Article
- (R)-Roscovitine and CFTR modulators enhance killing of multi-drug resistant Burkholderia cenocepacia by cystic fibrosis macrophages.Scientific reports · 2020Article
- Metabolomics profiling of tobacco exposure in children with cystic fibrosis.Journal of cystic fibrosis : official journal of the European Cystic Fibrosis Society · 2020Article
- Review
- Consequences of CRISPR-Cas9-Mediated CFTR Knockout in Human Macrophages.Frontiers in immunology · 2020Article
- Adapting Proteostasis and Autophagy for Controlling the Pathogenesis of Cystic Fibrosis Lung Disease.Frontiers in pharmacology · 2019Review
- Transglutaminases in Monocytes and Macrophages.Medical sciences (Basel, Switzerland) · 2018Review
- Cystic fibrosis transmembrane conductance regulator (CFTR) modulators have differential effects on cystic fibrosis macrophage function.Scientific reports · 2018Article
- Dietary cysteamine hydrochloride protects against oxidation, inflammation, and mucosal barrier disruption of broiler chickens challenged with Clostridium perfringens.Journal of animal science · 2018Article
Corrections and comments
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Authors and funding
9 authors at 2 institutions in 1 country.
Funding
Abstract
Members of the Burkholderia cepacia complex are virulent, multi-drug resistant pathogens that survive and replicate intracellularly in patients with cystic fibrosis (CF). We have discovered that B. cenocepacia cannot be cleared from CF macrophages due to defective autophagy, causing continued systemic inflammation and infection. Defective autophagy in CF is mediated through constitutive reactive oxygen species (ROS) activation of transglutaminase-2 (TG2), which causes the sequestration (accumulation) of essential autophagy initiating proteins. Cysteamine is a TG2 inhibitor and proteostasis regulator with the potential to restore autophagy. Therefore, we sought to examine the impact of cysteamine on CF macrophage autophagy and bacterial killing. Human peripheral blood monocyte-derived macrophages (MDMs) and alveolar macrophages were isolated from CF and non-CF donors. Macrophages were infected with clinical isolates of relevant CF pathogens. Cysteamine caused direct bacterial growth killing of live B. cenocepacia, B. multivorans, P. aeruginosa and MRSA in the absence of cells. Additionally, B. cenocepacia, B. multivorans, and P. aeruginosa invasion were significantly decreased in CF MDMs treated with cysteamine. Finally, cysteamine decreased TG2, p62, and beclin-1 accumulation in CF, leading to increased Burkholderia uptake into autophagosomes, increased macrophage CFTR expression, and decreased ROS and IL-1β production. Cysteamine has direct anti-bacterial growth killing and improves human CF macrophage autophagy resulting in increased macrophage-mediated bacterial clearance, decreased inflammation, and reduced constitutive ROS production. Thus, cysteamine may be an effective adjunct to antibiotic regimens in CF.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.