Distinct Responses of Cystic Fibrosis Epithelial Cells to SARS-CoV-2 and Influenza A Virus.

The COVID-19 pandemic has underscored the impact of viral infections on individuals with cystic fibrosis (CF). Initial observations suggested lower COVID-19 rates among CF populations; however, subsequent clinical data have presented a more complex scenario. This study aimed to investigate how bronchial epithelial cells from CF and non-CF individuals, including various CF transmembrane conductance regulator (CFTR) mutations, respond to infection with SARS-CoV-2 variants and SARS-CoV.

Improving the Predictive Value of Preclinical Mouse Models of Pseudomonas aeruginosa Respiratory Infection to Evaluate Antibiotic Efficacy.

Disease-specific animal models and treatment regimens are essential to optimize anti-Pseudomonas drug testing. Mouse models of acute and chronic P. aeruginosa infections provide valuable resources that mimic the initial and progressive bronchopulmonary infection typically observed in a wide range of patients - in hospital settings, with cystic fibrosis or chronic obstructive pulmonary disease.

Mutual Effects of Single and Combined CFTR Modulators and Bacterial Infection in Cystic Fibrosis.

Cystic fibrosis transmembrane conductance regulator (CFTR) modulators improve clinical outcomes with varied efficacies in patients with CF. However, the mutual effects of CFTR modulators and bacterial adaptation, together with antibiotic regimens, can influence clinical outcomes. We evaluated the effects of ivacaftor (IVA), lumacaftor (LUM), tezacaftor, elexacaftor, and a three-modulator combination of elexacaftor, tezacaftor, and ivacaftor (ETI), alone or combined with antibiotics, on sequential CF isolates.

Elastase Contributes to the Establishment of Chronic Lung Colonization and Modulates the Immune Response in a Murine Model.

Chronic infection by in cystic fibrosis (CF) patients is a major contributor to progressive lung damage and is poorly treated by available antibiotic therapy. An alternative approach to the development of additional antibiotic treatments is to identify complementary therapies which target bacterial virulence factors necessary for the establishment and/or maintenance of the chronic infection. The elastase (LasB) has been suggested as an attractive anti-virulence target due to its extracellular location, its harmful degradative effects on host tissues and the immune system, and the potential to inhibit its activity using small molecule inhibitors.

Genome-Based Approach Delivers Vaccine Candidates Against .

High incidence, severity and increasing antibiotic resistance characterize infections, highlighting the need for new therapeutic options. Vaccination strategies to prevent or limit infections represent a rational approach to positively impact the clinical outcome of risk patients; nevertheless this bacterium remains a challenging vaccine target. To identify novel vaccine candidates, we started from the genome sequence analysis of the reference strain PAO1 exploring the reverse vaccinology approach integrated with additional bioinformatic tools.

Efficacy of the Novel Antibiotic POL7001 in Preclinical Models of Pseudomonas aeruginosa Pneumonia.

The clinical development of antibiotics with a new mode of action combined with efficient pulmonary drug delivery is a priority against untreatable Pseudomonas aeruginosa lung infections. POL7001 is a macrocycle antibiotic belonging to the novel class of protein epitope mimetic (PEM) molecules with selective and potent activity against P. aeruginosa We investigated ventilator-associated pneumonia (VAP) and cystic fibrosis (CF) as indications of the clinical potential of POL7001 to treat P.

Comparative genomics and biological characterization of sequential Pseudomonas aeruginosa isolates from persistent airways infection.

Background: Pseudomonas aeruginosa establishes life-long chronic airway infections in cystic fibrosis (CF) patients. As the disease progresses, P. aeruginosa pathoadaptive variants are distinguished from the initially acquired strain.

Antibiotic pressure compensates the biological cost associated with Pseudomonas aeruginosa hypermutable phenotypes in vitro and in a murine model of chronic airways infection.

Objectives: Hypermutable strains of Pseudomonas aeruginosa frequently emerge during chronic airways infection in cystic fibrosis (CF) patients. While the increased accumulation of mutations by hypermutable strains determines a biological cost for the colonization of secondary environments, the mutator phenotypes might confer a selective advantage under antibiotic treatment in a CF airways environment.

Methods: To test this hypothesis, the reference strain PAO1 and clonal pairs of CF clinical hypermutable and wild-type P.

Neural stem cell gene therapy ameliorates pathology and function in a mouse model of globoid cell leukodystrophy.

Murine neural stem cells (mNSCs), either naive or genetically modified to express supranormal levels of β-galactocerebrosidase (GALC), were transplanted into the brain of Twitcher mice, a murine model of globoid cell leukodystrophy, a severe sphingolipidosis. Cells engrafted long-term into the host cytoarchitecture, producing functional GALC. Levels of enzyme activity in brain and spinal cord tissues were enhanced when GALC-overexpressing NSC were used.