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Introduction: Cystic fibrosis (CF) is caused by defective Cystic Fibrosis Transmembrane Conductance Regulator (CFTR) proteins. CFTR controls chloride (Cl - ) and bicarbonate (HCO 3 - ) transport into the Airway Surface Liquid (ASL). We investigated the impact of F508del-CFTR correction on HCO 3 - secretion by studying transepithelial HCO 3 - fluxes. Methods: HCO 3 - secretion was measured by pH-stat technique in primary human respiratory epithelial cells from healthy subjects (WT) and people with CF (pwCF) carrying at least one F508del variant. Its changes after CFTR modulation by the triple combination VX445/661/770 and in the context of TNF-α+IL-17 induced inflammation were correlated to ASL pH and transcriptional levels of CFTR and other HCO 3 - transporters of airway epithelia such as SLC26A4 (Pendrin), SLC26A9 and NBCe1. Results: CFTR-mediated HCO 3 - secretion was not detected in F508del primary human respiratory epithelial cells. It was rescued up to ∼ 80% of the WT level by VX-445/661/770. In contrast, TNF-α+IL-17 normalized transepithelial HCO 3 - transport and increased ASL pH. This was related to an increase in SLC26A4 and CFTR transcript levels. VX-445/661/770 induced an increase in pH only in the context of inflammation. Effects on HCO 3 - transport were not different between F508del homozygous and F508del compound heterozygous CF airway epithelia. Conclusion: Our studies show that correction of F508del-CFTR HCO 3 - is not sufficient to buffer acidic ASL and inflammation is a key regulator of HCO 3 - secretion in CF airways. Prediction of the response to CFTR modulators by theratyping should take into account airway inflammation., Competing Interests: IS-G reports support for the present manuscript from Vaincre la Mucoviscidose and Mucoviscidose ABCF2. IS-G also reports, outside the submitted work, grants from Agence Nationale pour la Recherche, Assistance Publique– Hôpitaux de Paris and Vertex Innovation Award, and consulting fees and travel support from Vertex therapeutics. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Zajac, Lepissier, Dréano, Chevalier, Hatton, Kelly-Aubert, Guidone, Planelles, Edelman, Girodon, Hinzpeter, Crambert, Pranke, Galietta and Sermet-Gaudelus.)

The valorization of poultry byproducts, like feathers (processed to feather meal), in animal feed could contribute to the presence of veterinary drugs, including antibiotics. An animal study was carried out to study the fate of sulfadiazine, trimethoprim, and oxytetracycline in feathers, plasma, and droppings of broiler chickens. Cage and floor housing, different from current farm practices, were studied. Samples were analyzed by liquid chromatography-tandem mass spectrometry (LC-MS/MS). A longer presence of antibiotics was observed in feathers compared to plasma, with sulfadiazine being present the most. The internal presence (via blood) and the external presence (via droppings) of antibiotics in/on feathers were shown. Analysis of Escherichia coli populations, from droppings and feathers, highlighted that resistant bacteria could be transferred from droppings to feathers in floor-housed animals. The overall results suggest that feathers are a potential reservoir of antimicrobial residues and could contribute to the selection of antibiotic-resistant bacteria in the environment, animals, and humans.

Poultry feathers are nowadays partially re-introduced into the animal food chain and the environment. They are valorised by their transformation into feather meal in order to be used as fertilisers in agriculture but also in animal feed (in particular, pet food and fish feed). However, unlike food producing animals for humans, feathers from poultry animals are not subject to a ban or regulatory limits on the presence of antibiotic residue after veterinary treatment. Feathers could therefore be a potential reservoir of antibiotic residues, unintentionally exposing the environment and animals through food, which might contribute to the emergence of antibiotic resistance. To this end, a multi-class liquid chromatographic method coupled with tandem mass spectrometry (LC-MS/MS) was developed for the detection and determination of residues of 30 antibiotics from eight groups of antibacterial (quinolones, lincosamides, macrolides, penicillins, phenicols, tetracyclines, sulphonamides and diaminopyrimidines) in feathers. The extraction of the analytes from the feathers was carried out by the salting out technique. The separation of the analytes employed a Kinetex C18 column. Quantification was made using internal standards. All analytes have been validated according to the performance criteria of Decision 2002/657/EC. Trueness of the method ranged from to 93% to 111% for all analytes and intermediate precision were to 1.2-18.8%. The limits of quantification (LOQ) were from 13 to 150 µg kg -1 depending on the analytes. The method is suitable for the monitoring and quantification of antibiotic residues in feathers over the range 13-600 µg kg -1 depending on the compound.