High-level antibiotic tolerance of a clinically-isolated Enterococcus faecalis strain.

Appl Environ Microbiol. 2020 Oct 23;:

Authors: Gu H, Roy S, Zheng X, Gao T, Ma H, Soultan Z, Fortner C, Nangia S, Ren D

Abstract
Bacteria can survive antibiotic treatment both by acquiring antibiotic resistance genes, and through mechanisms of tolerance that are based on phenotypic changes and the formation of metabolically inactive cells. Here, we report an Enterococcus faecalis strain (E. faecalis UM001B) isolated from a cystic fibrosis patient that has no increase in resistance but extremely high-level tolerance to ampicillin, vancomycin, and tetracycline. Specifically, the percentage of cells that survive 3.5-h antibiotic treatment (at 100 μg ⋅mL-1) is 25.4 ± 4.3% and 51.9 ± 4.0% for ampicillin and tetracycline, respectively; and vancomycin does not exhibit any significant killing. Consistent with the change in antibiotic susceptibility, UM001B is found to have reduced penetration of ampicillin and vancomycin, and accumulation of tetracycline compared to the reference strain ATCC29212. Based on whole-genome sequencing (WGS), four amino acid variants are identified in one of the tetracycline efflux pump repressors (TetRs) compared to ATCC29212. Results of molecular simulations and experimental assays reveal that these mutations can lead to a higher level of tetracycline efflux activity. Consistently, replicating these mutations in Escherichia coli MG1655 increases its tolerance to tetracycline. Overall, these findings provide new insights into the development of multidrug tolerance in E. faecalis, which can help future studies to better control enterococcal infections.IMPORTANCE. Enterococcus faecalis represents a major group of pathogens causing nosocomial infections that are resistant to multiple classes of antibiotics. An important challenge associated with E. faecalis infection is the emergence of multidrug tolerant strains, which have normal minimum inhibitory concentrations (MICs) but do not respond to antibiotic treatment. Here, we report a strain of E. faecalis isolated from a cystic fibrosis patient that demonstrates high-level tolerance to ampicillin, vancomycin, and tetracycline. Whole-genome sequencing reveals critical variants in one of the tetracycline efflux pump repressors, consistent with the increased tolerance of E. faecalis UM001B to tetracycline. These findings provide new information about bacterial antibiotic tolerance and may help develop more effective therapeutics.

PMID: 33097497 [PubMed - as supplied by publisher]

The NHS virtual gym boosting fitness and social connections for cystic fibrosis patients.

BMJ. 2020 Oct 23;371:m4063

Authors: Wilkinson E

PMID: 33097480 [PubMed - as supplied by publisher]

Identification of AAV serotypes for lung gene therapy in human embryonic stem cell-derived lung organoids.

Stem Cell Res Ther. 2020 Oct 23;11(1):448

Authors: Meyer-Berg H, Zhou Yang L, Pilar de Lucas M, Zambrano A, Hyde SC, Gill DR

Abstract
Gene therapy is being investigated for a range of serious lung diseases, such as cystic fibrosis and emphysema. Recombinant adeno-associated virus (rAAV) is a well-established, safe, viral vector for gene delivery with multiple naturally occurring and artificial serotypes available displaying alternate cell, tissue, and species-specific tropisms. Efficient AAV serotypes for the transduction of the conducting airways have been identified for several species; however, efficient serotypes for human lung parenchyma have not yet been identified. Here, we screened the ability of multiple AAV serotypes to transduce lung bud organoids (LBOs)-a model of human lung parenchyma generated from human embryonic stem cells. Microinjection of LBOs allowed us to model transduction from the luminal surface, similar to dosing via vector inhalation. We identified the naturally occurring rAAV2 and rAAV6 serotypes, along with synthetic rAAV6 variants, as having tropism for the human lung parenchyma. Positive staining of LBOs for surfactant proteins B and C confirmed distal lung identity and suggested the suitability of these vectors for the transduction of alveolar type II cells. Our findings establish LBOs as a new model for pulmonary gene therapy and stress the relevance of LBOs as a viral infection model of the lung parenchyma as relevant in SARS-CoV-2 research.

PMID: 33097094 [PubMed - as supplied by publisher]

18 new pubmed citations were retrieved for your search. Click on the search hyperlink below to display the complete search results:

"Cystic Fibrosis"

These pubmed results were generated on 2020/10/24

PubMed comprises more than millions of citations for biomedical literature from MEDLINE, life science journals, and online books. Citations may include links to full-text content from PubMed Central and publisher web sites.

Biodistribution and elimination pathways of PEGylated recombinant human deoxyribonuclease I after pulmonary delivery in mice.

J Control Release. 2020 Oct 19;:

Authors: Mahri S, Rondon A, Wilms T, Bosquillon C, Vanbever R

Abstract
Conjugation of recombinant human deoxyribonuclease I (rhDNase) to polyethylene glycol (PEG) of 20 to 40 kDa was previously shown to prolong the residence time of rhDNase in the lungs of mice after pulmonary delivery while preserving its full enzymatic activity. This work aimed to study the fate of native and PEGylated rhDNase in the lungs and to elucidate their biodistribution and elimination pathways after intratracheal instillation in mice. In vivo fluorescence imaging revealed that PEG30 kDa-conjugated rhDNase (PEG30-rhDNase) was retained in mouse lungs for a significantly longer period of time than native rhDNase (12 days vs 5 days). Confocal microscopy confirmed the presence of PEGylated rhDNase in lung airspaces for at least 7 days. In contrast, the unconjugated rhDNase was cleared from the lung lumina within 24 h and was only found in the lung parenchyma and alveolar macrophages thereafter. Systemic absorption of intact rhDNase and PEG30-rhDNase was observed. However, this was significantly lower for the latter. Catabolism, primarily in the lungs and secondarily systemically followed by renal excretion of byproducts were the predominant elimination pathways for both native and PEGylated rhDNase. Catabolism was nevertheless more extensive for the native protein. On the other hand, mucociliary clearance appeared to play a less prominent role in the clearance of those proteins after pulmonary delivery. The prolonged presence of PEGylated rhDNase in lung airspaces appears ideal for its mucolytic action in cystic fibrosis patients.

PMID: 33091532 [PubMed - as supplied by publisher]

LocusFocus: Web-based colocalization for the annotation and functional follow-up of GWAS.

PLoS Comput Biol. 2020 Oct 22;16(10):e1008336

Authors: Panjwani N, Wang F, Mastromatteo S, Bao A, Wang C, He G, Gong J, Rommens JM, Sun L, Strug LJ

Abstract
Genome-wide association studies (GWAS) have primarily identified trait-associated loci in the non-coding genome. Colocalization analyses of SNP associations from GWAS with expression quantitative trait loci (eQTL) evidence enable the generation of hypotheses about responsible mechanism, genes and tissues of origin to guide functional characterization. Here, we present a web-based colocalization browsing and testing tool named LocusFocus (https://locusfocus.research.sickkids.ca). LocusFocus formally tests colocalization using our established Simple Sum method to identify the most relevant genes and tissues for a particular GWAS locus in the presence of high linkage disequilibrium and/or allelic heterogeneity. We demonstrate the utility of LocusFocus, following up of a genome-wide significant locus from a GWAS of meconium ileus (an intestinal obstruction in cystic fibrosis). Using LocusFocus for colocalization analysis with eQTL data suggests variation in ATP12A gene expression in the pancreas rather than intestine is responsible for the GWAS locus. LocusFocus has no operating system dependencies and may be installed in a local web server. LocusFocus is available under the MIT license, with full documentation and source code accessible on GitHub at https://github.com/naim-panjwani/LocusFocus.

PMID: 33090994 [PubMed - as supplied by publisher]

Dyschromic Nails, Exertional Dyspnea, and Lower Extremity Edema.

JAMA. 2020 Oct 22;:

Authors: Chatterjee S, Dasenbrook EC

PMID: 33090179 [PubMed - as supplied by publisher]

Lipidome Alterations Induced by Cystic Fibrosis, CFTR Mutation, and Lung Function.

J Proteome Res. 2020 Oct 22;:

Authors: Zardini Buzatto A, Abdel Jabar M, Nizami I, Dasouki M, Li L, Abdel Rahman AM

Abstract
Cystic fibrosis is a genetic pathology characterized by abnormal accumulation of mucus in the respiratory, gastrointestinal, and reproductive tracts, caused by mutations in the CFTR gene. Although the classical presentation of the condition is well known, there is still a need for a better characterization of metabolic alterations related to cystic fibrosis and different genotypic mutations. We employed untargeted, comprehensive lipidomics of blood serum samples to investigate alterations in the lipid metabolism related to the pathology, mutation classes, and lung function decline. Six unique biomarker candidates were able to independently differentiate diseased individuals from healthy controls with excellent performance. Cystic fibrosis patients showed dyslipidemia for most lipid subclasses, with significantly elevated odd-chain and polyunsaturated fatty acyl lipids. Phosphatidic acids and diacylglycerols were particularly affected by different genotypic mutation classes. We selected a biomarker panel composed of four lipids, including two ceramides, one sphingomyelin, and one fatty acid, which correctly classified all validation samples from classes III and IV. A biomarker panel of five oxidized lipids was further selected to differentiate patients with reduced lung function, measured as predicted FEV1%. Our results indicate that cystic fibrosis is deeply related to lipid metabolism and provide new clues for the investigation of the disease mechanisms and therapeutic targets.

PMID: 33089695 [PubMed - as supplied by publisher]

Early-onset autoimmunity associated with SOCS1 haploinsufficiency.

Nat Commun. 2020 Oct 21;11(1):5341

Authors: Hadjadj J, Castro CN, Tusseau M, Stolzenberg MC, Mazerolles F, Aladjidi N, Armstrong M, Ashrafian H, Cutcutache I, Ebetsberger-Dachs G, Elliott KS, Durieu I, Fabien N, Fusaro M, Heeg M, Schmitt Y, Bras M, Knight JC, Lega JC, Lesca G, Mathieu AL, Moreews M, Moreira B, Nosbaum A, Page M, Picard C, Ronan Leahy T, Rouvet I, Ryan E, Sanlaville D, Schwarz K, Skelton A, Viallard JF, Viel S, Villard M, Callebaut I, Picard C, Walzer T, Ehl S, Fischer A, Neven B, Belot A, Rieux-Laucat F

Abstract
Autoimmunity can occur when a checkpoint of self-tolerance fails. The study of familial autoimmune diseases can reveal pathophysiological mechanisms involved in more common autoimmune diseases. Here, by whole-exome/genome sequencing we identify heterozygous, autosomal-dominant, germline loss-of-function mutations in the SOCS1 gene in ten patients from five unrelated families with early onset autoimmune manifestations. The intracellular protein SOCS1 is known to downregulate cytokine signaling by inhibiting the JAK-STAT pathway. Accordingly, patient-derived lymphocytes exhibit increased STAT activation in vitro in response to interferon-γ, IL-2 and IL-4 that is reverted by the JAK1/JAK2 inhibitor ruxolitinib. This effect is associated with a series of in vitro and in vivo immune abnormalities consistent with lymphocyte hyperactivity. Hence, SOCS1 haploinsufficiency causes a dominantly inherited predisposition to early onset autoimmune diseases related to cytokine hypersensitivity of immune cells.

PMID: 33087723 [PubMed - in process]

Protein kinase CK2 and ion channels (Review).

Biomed Rep. 2020 Dec;13(6):55

Authors: Montenarh M, Götz C

Abstract
Protein kinase CK2 appears as a tetramer or higher molecular weight oligomer composed of catalytic CK2α, CK2α' subunits and non-catalytic regulatory CK2β subunits or as individual subunits. It is implicated in a variety of different regulatory processes, such as Akt signalling, splicing and DNA repair within eukaryotic cells. The present review evaluates the influence of CK2 on ion channels in the plasma membrane. CK2 phosphorylates platform proteins such as calmodulin and ankyrin G, which bind to channel proteins for a physiological transport to and positioning into the membrane. In addition, CK2 directly phosphorylates a variety of channel proteins directly to regulate opening and closing of the channels. Thus, modulation of CK2 activities by specific inhibitors, by siRNA technology or by CRISPR/Cas technology has an influence on intracellular ion concentrations and thereby on cellular signalling. The physiological regulation of the intracellular ion concentration is important for cell survival and correct intracellular signalling. Disturbance of this regulation results in a variety of different diseases including epilepsy, heart failure, cystic fibrosis and diabetes. Therefore, these effects should be considered when using CK2 inhibition as a treatment option for cancer.

PMID: 33082952 [PubMed]

Single Cell Analysis of Drug Susceptibility of Mycobacterium Abscessus During Macrophage Infection.

Antibiotics (Basel). 2020 Oct 17;9(10):

Authors: Brzostek J, Fatin A, Chua WH, Tan HY, Dick T, Gascoigne NRJ

Abstract
Mycobacterium abscessus is an emerging health risk to immunocompromised individuals and to people with pre-existing pulmonary conditions. As M. abscessus possesses multiple mechanisms of drug resistance, treatments of M. abscessus are of poor efficacy. Therefore, there is an urgent need for new therapeutic strategies targeting M. abscessus. We describe an experimental system for screening of compounds for their antimicrobial activity against intracellular M. abscessus using flow cytometry and imaging flow cytometry. The assay allows simultaneous analysis of multiple parameters, such as proportion of infected host cells, bacterial load per host cell from the infected population, and host cell viability. We verified the suitability of this method using two antibiotics with known activity against M. abscessus: clarithromycin and amikacin. Our analysis revealed a high degree of infection heterogeneity, which correlated with host cell size. A higher proportion of the larger host cells is infected with M. abscessus as compared to smaller host cells, and infected larger cells have higher intracellular bacterial burden than infected smaller cells. Clarithromycin treatment has a more pronounced effect on smaller host cells than on bigger host cells, suggesting that heterogeneity within the host cell population has an effect on antibiotic susceptibility of intracellular bacteria.

PMID: 33080864 [PubMed]

Evaluation of both exonic and intronic variants for effects on RNA splicing allows for accurate assessment of the effectiveness of precision therapies.

PLoS Genet. 2020 Oct 21;16(10):e1009100

Authors: Joynt AT, Evans TA, Pellicore MJ, Davis-Marcisak EF, Aksit MA, Eastman AC, Patel SU, Paul KC, Osorio DL, Bowling AD, Cotton CU, Raraigh KS, West NE, Merlo CA, Cutting GR, Sharma N

Abstract
Elucidating the functional consequence of molecular defects underlying genetic diseases enables appropriate design of therapeutic options. Treatment of cystic fibrosis (CF) is an exemplar of this paradigm as the development of CFTR modulator therapies has allowed for targeted and effective treatment of individuals harboring specific genetic variants. However, the mechanism of these drugs limits effectiveness to particular classes of variants that allow production of CFTR protein. Thus, assessment of the molecular mechanism of individual variants is imperative for proper assignment of these precision therapies. This is particularly important when considering variants that affect pre-mRNA splicing, thus limiting success of the existing protein-targeted therapies. Variants affecting splicing can occur throughout exons and introns and the complexity of the process of splicing lends itself to a variety of outcomes, both at the RNA and protein levels, further complicating assessment of disease liability and modulator response. To investigate the scope of this challenge, we evaluated splicing and downstream effects of 52 naturally occurring CFTR variants (exonic = 15, intronic = 37). Expression of constructs containing select CFTR intronic sequences and complete CFTR exonic sequences in cell line models allowed for assessment of RNA and protein-level effects on an allele by allele basis. Characterization of primary nasal epithelial cells obtained from individuals harboring splice variants corroborated in vitro data. Notably, we identified exonic variants that result in complete missplicing and thus a lack of modulator response (e.g. c.2908G>A, c.523A>G), as well as intronic variants that respond to modulators due to the presence of residual normally spliced transcript (e.g. c.4242+2T>C, c.3717+40A>G). Overall, our data reveals diverse molecular outcomes amongst both exonic and intronic variants emphasizing the need to delineate RNA, protein, and functional effects of each variant in order to accurately assign precision therapies.

PMID: 33085659 [PubMed - as supplied by publisher]

Membrane-bound mucins of the airway mucosal surfaces are densely decorated with keratan sulfate: revisiting their role in the Lung's innate defense.

Glycobiology. 2020 Sep 21;:

Authors: Carpenter J, Kesimer M

Abstract
Understanding the basic elements of the airway mucosal surfaces and how they form a functional barrier is essential in understanding disease initiation, progression, pathogenesis and ultimately treating chronic lung diseases. Using primary airway epithelial cell cultures, atomic force microscopy (AFM), multiangle light scattering, and quartz crystal micro balance with dissipation monitoring (QCMD) techniques, here we report that the membrane bound mucins (MBMs) found in the periciliary layer (PCL) of the airway surface are densely decorated with keratan sulfate (KS). AFM and immunoblotting show that the KS sidechains can be removed enzymatically with keratanase II (KII) treatment and the antibody accessibility for B2729 (MUC1), MUCH4 (MUC4), OC125 (MUC16) was substantially enhanced. Light scattering analysis confirmed that KII treatment removed ~ 40% of the mass from the mucin fractions. Surface binding experiments indicated that MBMs were able to pack into a tighter conformation following KS removal, suggesting that negatively charged KS sidechains play a role in mucin-mucin repulsion and contribute to "space filling" in the PCL. We also observed that soluble filtrate from the common airway pathogen Pseudomonas aeruginosa is capable of stripping KS from MBMs. Together, our findings indicate that KS glycosylation of MBMs may play an important role in the integrity of the airway mucosal barrier and its compromise in disease.

PMID: 33083824 [PubMed - as supplied by publisher]

Micron Scale Spatial Measurement of the O2 Gradient Surrounding a Bacterial Biofilm in Real Time.

mBio. 2020 Oct 20;11(5):

Authors: Klementiev AD, Jin Z, Whiteley M

Abstract
Bacteria alter their local chemical environment through both consumption and the production of a variety of molecules, ultimately shaping the local ecology. Molecular oxygen (O2) is a key metabolite that affects the physiology and behavior of virtually all bacteria, and its consumption often results in O2 gradients within sessile bacterial communities (biofilms). O2 plays a critical role in several bacterial phenotypes, including antibiotic tolerance; however, our understanding of O2 levels within and surrounding biofilms has been hampered by the difficulties in measuring O2 levels in real-time for extended durations and at the micron scale. Here, we developed electrochemical methodology based on scanning electrochemical microscopy to quantify the O2 gradients present above a Pseudomonas aeruginosa biofilm. These results reveal that a biofilm produces a hypoxic zone that extends hundreds of microns from the biofilm surface within minutes and that the biofilm consumes O2 at a maximum rate. Treating the biofilm with levels of the antibiotic ciprofloxacin that kill 99% of the bacteria did not affect the O2 gradient, indicating that the biofilm is highly resilient to antimicrobial treatment in regard to O2 consumption.IMPORTANCE O2 is a fundamental environmental metabolite that affects all life on earth. While toxic to many microbes and obligately required by others, those that have appropriate physiological responses survive and can even benefit from various levels of O2, particularly in biofilm communities. Although most studies have focused on measuring O2 within biofilms, little is known about O2 gradients surrounding biofilms. Here, we developed electrochemical methodology based on scanning electrochemical microscopy to measure the O2 gradients surrounding biofilms in real time on the micron scale. Our results reveal that P. aeruginosa biofilms produce a hypoxic zone that can extend hundreds of microns from the biofilm surface and that this gradient remains even after the addition of antibiotic concentrations that eradicated 99% of viable cells. Our results provide a high resolution of the O2 gradients produced by P. aeruginosa biofilms and reveal sustained O2 consumption in the presence of antibiotics.

PMID: 33082251 [PubMed - in process]

The evolution of virulence in Pseudomonas aeruginosa during chronic wound infection.

Proc Biol Sci. 2020 Oct 28;287(1937):20202272

Authors: Vanderwoude J, Fleming D, Azimi S, Trivedi U, Rumbaugh KP, Diggle SP

Abstract
Opportunistic pathogens are associated with a number of chronic human infections, yet the evolution of virulence in these organisms during chronic infection remains poorly understood. Here, we tested the evolution of virulence in the human opportunistic pathogen Pseudomonas aeruginosa in a murine chronic wound model using a two-part serial passage and sepsis experiment, and found that virulence evolved in different directions in each line of evolution. We also assessed P. aeruginosa adaptation to a chronic wound after 42 days of evolution and found that morphological diversity in our evolved populations was limited compared with that previously described in cystic fibrosis (CF) infections. Using whole-genome sequencing, we found that genes previously implicated in P. aeruginosa pathogenesis (lasR, pilR, fleQ, rpoN and pvcA) contained mutations during the course of evolution in wounds, with selection occurring in parallel across all lines of evolution. Our findings highlight that: (i) P. aeruginosa heterogeneity may be less extensive in chronic wounds than in CF lungs; (ii) genes involved in P. aeruginosa pathogenesis acquire mutations during chronic wound infection; (iii) similar genetic adaptations are employed by P. aeruginosa across multiple infection environments; and (iv) current models of virulence may not adequately explain the diverging evolutionary trajectories observed in an opportunistic pathogen during chronic wound infection.

PMID: 33081616 [PubMed - in process]

Which score is better in association with exercise capacity and health status in non-cystic fibrosis bronchiectasis patients?

Turk J Med Sci. 2020 Oct 21;:

Authors: Varol Y, DoĞan Şahİn H, Aksel N, Çirak AK

Abstract
BACKGROUND/AIM: Two different scoring systems were developed to determine the severity of bronchiectasis: 1. FACED scoring 2. Bronchiectasis Severity Index (BSI). In this study, we aim to compare these two scoring systems according to the 6-minute walking distance and disease-specific health status questionnaire in patients with non-cystic fibrosis bronchiectasis (NCFB).
MATERIALS AND METHODS: Smoking history, emergency and hospital admissions, body mass index were obtained from NCFB patients admitted to our hospitals? pulmonary rehabilitation unit between 2013 and 2018. Detailed pulmonary function tests were performed to all participants. Dyspnea perceptions were determined according to mMRC dyspnea scale. 6 minutes? walk test was used to determine exercise capacity. Saint George Respiratory Questionnaire (SGRQ) was applied to determine health status. Both FACED and BSI scores were calculated for all participants.
RESULTS: There were a total of 183 participants, 153 of whom were men. A significant and strong correlation was found between FACED and BSI scores. As the severity of bronchiectasis increased, walking distance was significantly decreased and health status was significantly worsened by both FACED and BSI scoring. A statistically significant but weak negative correlation was found between FACED score and walking distance. There was a significant negative correlation between BSI and walking distance and a stronger negative correlation than FACED. Similarly, there was a significant negative correlation between health status and both FACED and BSI, but this correlation was stronger in the BSI score.
CONCLUSION: Although both FACED and BSI scores were negatively correlated with walking distance and health status in patients with NCFB, BSI was more associated.

PMID: 33081435 [PubMed - as supplied by publisher]

22 new pubmed citations were retrieved for your search. Click on the search hyperlink below to display the complete search results:

"Cystic Fibrosis"

These pubmed results were generated on 2020/10/21

PubMed comprises more than millions of citations for biomedical literature from MEDLINE, life science journals, and online books. Citations may include links to full-text content from PubMed Central and publisher web sites.

43 new pubmed citations were retrieved for your search. Click on the search hyperlink below to display the complete search results:

"Cystic Fibrosis"

These pubmed results were generated on 2020/10/21

PubMed comprises more than millions of citations for biomedical literature from MEDLINE, life science journals, and online books. Citations may include links to full-text content from PubMed Central and publisher web sites.

45 new pubmed citations were retrieved for your search. Click on the search hyperlink below to display the complete search results:

"Cystic Fibrosis"

These pubmed results were generated on 2020/10/19

PubMed comprises more than millions of citations for biomedical literature from MEDLINE, life science journals, and online books. Citations may include links to full-text content from PubMed Central and publisher web sites.

Mucin secretion in cystic fibrosis - a systematic review.

Dig Dis. 2020 Oct 13;:

Authors: Niv Y, Ho SB, Rokkas T

Abstract
Background Mucus protects the epithelium against invaders and toxic materials. Sticky and thick mucus is characteristic of CF. Objective The aim of this systematic review is to characterize the specific mucins secreted in the lung and intestinal tract of CF patients. Methods A systematic literature search was conducted up to 31.12.2019. The following terms were used: "cystic fibrosis" AND "mucin". Case control studies comparing mucin expression in CF patients to healthy controls were included. Results We found 741 eligible studies, 694 studies rejected because they were performed in animals and not in full text, and 32 studies were excluded being editorials, duplications, review articles, meta-analysis, or not in English. Fifteen studies were eligible for our study, including 150 CF patients compared to 82 healthy controls all fulfilled the inclusion criteria. The main mucin types expressed in the sinus sub-mucosal glands, sputum, trachea-bronchial surface epithelium and lung sub -mucosal glands were MUC5AC and MUC5B. Increase in the number of sinusoidal sub-mucosal glands and expression of MUC5B was found in CF patients, but no such difference from healthy controls was found for the number of goblet cells in the surface epithelium nor in the expression of MUC5AC. The opposite was found in the trachea-bronchial surface epithelium and in the lungs. Conclusions Increased expression of MUC5AC in the surface epithelium and of MUC5B in the sub-epithelial glands may be the result of higher secretion rate of mucin into the lumen of the respiratory tract, causing mucus plaque, infection and inflammation.

PMID: 33049746 [PubMed - as supplied by publisher]