The function of cystic fibrosis transmembrane conductance regulator (CFTR) channels is crucial in human airways. However unfortunately, chronic infection has been shown to impair CFTR proteins in non-CF airway epithelial cells (AEC) and to alter the efficiency of new treatments with CFTR modulators designed to correct the basic CFTR default in AEC from cystic fibrosis (CF) patients carrying the F508del mutation. Our aim was first to compare the effect of laboratory strains, clinical isolates, engineered and natural mutants to determine the role of the LasR quorum sensing system in CFTR impairment, and second, to test the efficiency of a quorum sensing inhibitor to counteract the deleterious impact of both on wt-CFTR and on the rescue of F508del-CFTR by correctors. We first report that exoproducts from either the laboratory PAO1 strain or a clinical ≪Early≫ isolate (from an early stage of infection) altered CFTR expression, localization and function in AEC expressing wt-CFTR. Genetic inactivation of the quorum-sensing LasR in PAO1 (PAO1Δ) or in a natural clinical mutant (≪Late≫ CF-adapted clinical isolate) abolished wt-CFTR impairment. PAO1 exoproducts also dampened F508del-CFTR rescue by VRT-325 or Vx-809 correctors in CF cells, whereas PAO1Δ had no impact. Importantly, treatment of cultures with a quorum sensing inhibitor (HDMF) prevented the negative effect of exoproducts on wt-CFTR and preserved CFTR rescue by correctors in CF AEC. These findings indicate that LasR-interfering strategies could be of benefits to counteract the deleterious effect of in infected patients.
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http://dx.doi.org/10.3389/fcimb.2017.00470 | DOI Listing |
Biotechnol Bioeng
January 2025
Department of Biochemistry, Molecular Biology and Biophysics, University of Minnesota, St. Paul, Minnesota, USA.
N-acyl l-homoserine lactones are signaling molecules used by numerous bacteria in quorum sensing. Some bacteria encode lactonases, which can inactivate these signals. Lactonases were reported to inhibit quorum sensing-dependent phenotypes, including virulence and biofilm.
View Article and Find Full Text PDFSci Rep
January 2025
Hubrecht Institute-KNAW and University Medical Center Utrecht, Utrecht, The Netherlands.
Pseudomonas aeruginosa is a Gram-negative bacterium that is notorious for airway infections in cystic fibrosis (CF) subjects. Bacterial quorum sensing (QS) coordinates virulence factor expression and biofilm formation at population level. Better understanding of QS in the bacterium-host interaction is required.
View Article and Find Full Text PDFInt J Food Microbiol
January 2025
Department of Food Science and Biotechnology, Dongguk University, Goyang 10326, Republic of Korea. Electronic address:
Spent coffee grounds (SCGs) have been explored for use as various bioresources, such as biofuels, and are known to possess biological functions, including antioxidant activity. However, the antibiofilm properties of SCGs against pathogenic bacteria have not been fully investigated. Therefore, this study aimed to highlight the inhibitory effects of SCG extract (SCGE) on biofilm formation in Listeria monocytogenes and investigated the underlying mechanisms.
View Article and Find Full Text PDFmBio
January 2025
State Key Laboratory for Crop Stress Resistance and High-Efficiency Production, Shaanxi Key Laboratory of Agricultural and Environmental Microbiology, College of Life Sciences, Northwest A&F University, Yangling, Shaanxi, China.
As a universal language across the bacterial kingdom, the quorum sensing signal autoinducer-2 (AI-2) can coordinate many bacterial group behaviors. However, unknown AI-2 receptors in bacteria may be more than what has been discovered so far, and there are still many unknown functions for this signal waiting to be explored. Here, we have identified a membrane-bound histidine kinase of the pathogenic bacterium , AsrK, as a receptor that specifically detects AI-2 under low boron conditions.
View Article and Find Full Text PDFCurr Med Chem
January 2025
Department of Electronics & Communication Engineering, Jaypee University of Information Technology, Solan, H.P., India.
A planktonic population of bacteria can form a biofilm by adhesion and colonization. Proteins known as "adhesins" can bind to certain environmental structures, such as sugars, which will cause the bacteria to attach to the substrate. Quorum sensing is used to establish the population is dense enough to form a biofilm.
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