Directed evolution of the resistance enzyme Cfr under antibiotic selection identifies increased Cfr expression and stability as strategies to boost resistance and reveals that Cfr modification of the ribosome confers resistance by sterically occluding binding of antibiotics.
Shikai Hu, Jacquelyn O Russell ... Satdarshan P Monga
Ductular reaction often observed in chronic liver pathologies such as in cystic fibrosis could be due to disruption of a novel complex of β-catenin-NF-κB and CFTR in cholangiocytes, which leads to persistent nuclear translocation of p65 and NF-κB activation.
Tannic acid acts as an ‘antidote’ against the negative effects of a bacterial enzyme, which can both aggravate cystic fibrosis and enable the anthrax bacteria to evade the immune responses elicited by a typical live vaccine.
Márton A Simon, Iordan Iordanov ... László Csanády
Functional studies on CFTR anion channels harboring combinations of catalytic site mutations in the active ATPase site reveal the true stability of the prehydrolytic open-pore state as well as nucleotide-binding domain interface features that are unique to human CFTR.
Ramanath Narayana Hegde, Seetharaman Parashuraman ... Alberto Luini
Analysis of the mechanism of action of cystic fibrosis corrector drugs reveals signalling pathways potently controlling the proteostasis of the main disease-relevant CFTR mutant.
Aqueous solubility of cystic fibrosis drug ivacaftor is ~200-fold lower, whereas the potency of its stimulatory effect on the CFTR channel is >100-fold higher, than reported, and is fully reversible.
ADGRG2, an orphan GPCR, when coupled to CFTR via a regional Gq signaling on the apical membrane, acts to regulate efferent duct fluid reabsorption making it essential for male fertility.
Coupling of CFTR pore opening to nucleotide binding domain dimerization does not depend on ATP binding, but is an inherent property of the channel protein and likely other ABC transporters.
Heledd H Jarosz-Griffiths, Thomas Scambler ... Daniel Peckham
CFTR modulators have potent innate anti-inflammatory properties that can be measured in clinic, both ex vivo and in vitro, which can be used to predict treatment efficacy.