CFTR, the Odd ABC Transporter Responsible for Cystic Fibrosis

Speaker Jue Chen, Ph.D., of The Rockefeller University, studies ATP-binding cassette (ABC) transporters, a diverse group of membrane proteins integral to almost every biological process. In prokaryotes, these proteins are critical for survival. In humans, ABC transporters make up one of the largest gene families, and more than a dozen genetic diseases have been traced to ABC transporter defects. ABC transporters are also central to multidrug resistance in many pathogenic bacteria and in tumor cells.For more information go tohttps://oir.nih.gov/walsAir date: 4/28/2021 3:00:00 PM
Source: Videocast - All Events - Category: General Medicine Tags: Upcoming Events Source Type: video

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In this study, we investigated if apoptotic body-like liposomes (ABLs) loaded with phosphatidylinositol 5-phosphate (PI5P), known to regulate actin dynamics and vesicular trafficking, could restore phagocytic machinery while limiting inflammatory response in in vitro and in vivo models of MDR P. aeruginosa infection. Our results show that the in vitro treatment with ABL carrying PI5P (ABL/PI5P) enhances bacterial uptake, ROS production, phagosome acidification, and intracellular bacterial killing in human monocyte-derived macrophages (MDMs) with pharmacologically inhibited cystic fibrosis transmembrane conductance regulato...
Source: Frontiers in Immunology - Category: Allergy & Immunology Source Type: research
In this study, the in vitro activities of various ceragenins against Achromobacter-species biofilms were investigated comparatively with a conventional antibiotic (meropenem). Biofilm-formation inhibition and biofilm-adhesion inhibition were investigated on five strong biofilm-producing strains. The lowest MIC50 result was obtained with CSA-13. All of the tested CSAs showed significant biofilm inhibitory activity in the manner of a time- and concentration-dependent effect. To the best of our knowledge, this is the first article to evaluate the antibacterial and antibiofilm activities of tested CSAs against Achromobact...
Source: Journal of Chemotherapy - Category: Cancer & Oncology Tags: J Chemother Source Type: research
Conclusions: This cohort of children with CF reveals that colonizing P. aeruginosa strains predominantly display resistance to several first-line antibiotics, although most isolates were susceptible to meropenem and tobramycin; 42.9% of isolates showed a phenotype consistent with adaptation to chronic lung infection.
Source: The Pediatric Infectious Disease Journal - Category: Infectious Diseases Tags: Original Studies Source Type: research
Chronic macrolides in cystic fibrosis (CF) are recommended in the CF Foundation care guidelines, particularly for individuals harboring Pseudomonas aeruginosa [1]. However, macrolide monotherapy may pose risks for development of drug-resistant bacteria, especially in nontuberculous mycobacteria (NTM) [2]. In CF, NTM infections –most frequently caused by Mycobacterium avium complex (MAC)–are increasing in prevalence [3] and have been associated with accelerated lung function decline [4]. Despite multidrug therapy, clinical outcomes for MAC in CF are often poor [4], and in non-CF patients, macrolide-resistant MAC...
Source: Journal of Cystic Fibrosis - Category: Respiratory Medicine Authors: Source Type: research
Stenotrophomonas maltophilia,Burkholderia cepacia complex,Elizabethkingia spp.,Chryseobacterium spp.,Achromobacter spp., andAlcaligenes spp. are less ‐common non–lactose‐fermenting bacteria that have emerged as important opportunistic pathogens. Patients at the highest risk for these infections include the immunocompromised, those with cystic fibrosis, and the critically ill. These opportunistic pathogens are frequently drug resistant throu gh the expression of β‐lactamases, multidrug efflux pumps, aminoglycoside‐modifying enzymes, and target site alterations discussed in detail throughout this review. A...
Source: Pharmacotherapy: The Journal of Human Pharmacology and Drug Therapy - Category: Drugs & Pharmacology Authors: Tags: Review Of Therapeutics Source Type: research
With the increase of infections due to multidrug resistant bacterial pathogens and the shortage of antimicrobial molecules with novel targets, interest in bacteriophages as a therapeutic option has regained much attraction. Before the launch of future clinical trials, in vitro studies are required to better evaluate the efficacies and potential pitfalls of such therapies. Here we studied in an ex vivo human airway epithelial cell line model the efficacy of phage and ciprofloxacin alone and in combination to treat infection by Pseudomonas aeruginosa. The Calu-3 cell line and the isogenic CFTR knock down cell line (cftr-) in...
Source: Frontiers in Microbiology - Category: Microbiology Source Type: research
The opportunistic pathogen Pseudomonas aeruginosa is responsible for much of the morbidity and mortality associated with cystic fibrosis (CF), a condition that predisposes patients to chronic lung infections. P. aeruginosa lung infections are difficult to treat because P. aeruginosa adapts to the CF lung, can develop multidrug resistance, and can form biofilms. Despite the clinical significance of P. aeruginosa, modeling P. aeruginosa infections in CF has been challenging. Here, we characterize Scnn1b-transgenic (Tg) BALB/c mice as P. aeruginosa lung infection models. Scnn1b-Tg mice overexpress the epithelial Na+ channel (...
Source: Infection and Immunity - Category: Infectious Diseases Authors: Tags: Bacterial Infections Source Type: research
Abstract Achromobacter is a genus of non-fermenting Gram negative bacteria under order Burkholderiales Although primarily isolated from respiratory tract of people with cystic fibrosis, Achromobacter spp. can cause a broad range of infections in hosts with other underlying conditions. Their rare occurrence and ever-changing taxonomy hinder defining their clinical features, risk factors for acquisition and adverse outcomes, and optimal treatment. Achromobacter spp. are intrinsically resistant to several antibiotics (e.g. most cephalosporins, aztreonam and aminoglycosides), and are increasingly acquiring resistance ...
Source: Antimicrobial Agents and Chemotherapy - Category: Microbiology Authors: Tags: Antimicrob Agents Chemother Source Type: research
Conclusions: This study enriches the understanding of MDR Achromobacter spp. epidemiology, confirms prevalence and chronic colonization of A. xylosoxidans in CF lungs. It presents in vitro data to support the efficacy of new combinations for use in the treatment of chronic Achromobacter infections. PMID: 32816722 [PubMed - as supplied by publisher]
Source: Antimicrobial Agents and Chemotherapy - Category: Microbiology Authors: Tags: Antimicrob Agents Chemother Source Type: research
Stenotrophomonas maltophilia,Burkholderia cepacia complex,Elizabethkingia spp.,Chryseobacterium spp.,Achromobacter spp., andAlcaligenes spp. are less ‐common non–lactose‐fermenting bacteria that have emerged as important opportunistic pathogens. Patients at the highest risk for these infections include the immunocompromised, those with cystic fibrosis, and the critically ill. These opportunistic pathogens are frequently drug resistant throu gh the expression of β‐lactamases, multidrug efflux pumps, aminoglycoside‐modifying enzymes, and target site alterations discussed in detail throughout this review. A...
Source: Pharmacotherapy: The Journal of Human Pharmacology and Drug Therapy - Category: Drugs & Pharmacology Authors: Tags: Review Of Therapeutics Source Type: research
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