A5035093422- Cystic Fibrosis Research Advances
- Bacterial biofilms and quorum sensing
- Antibiotic Resistance in Bacteria
- Asthma and respiratory diseases
- Inhalation and Respiratory Drug Delivery
- Pediatric health and respiratory diseases
- Neonatal Respiratory Health Research
- Antimicrobial Peptides and Activities
- Immune responses and vaccinations
- Respiratory viral infections research
- Gut microbiota and health
- Mycobacterium research and diagnosis
- Glutathione Transferases and Polymorphisms
- Pneumonia and Respiratory Infections
- Vibrio bacteria research studies
- Bacterial Genetics and Biotechnology
- Bacteriophages and microbial interactions
- Pharmaceutical and Antibiotic Environmental Impacts
- Immune Response and Inflammation
- Immunodeficiency and Autoimmune Disorders
- Tracheal and airway disorders
- Pneumocystis jirovecii pneumonia detection and treatment
- Microbial infections and disease research
- Interstitial Lung Diseases and Idiopathic Pulmonary Fibrosis
- Helicobacter pylori-related gastroenterology studies
Istituti di Ricovero e Cura a Carattere Scientifico
2015-2024
Istituto di Ricovero e Cura a Carattere Scientifico San Raffaele
2015-2024
Vita-Salute San Raffaele University
2015-2024
University College Dublin
2023
IRCCS Ospedale San Raffaele
2008-2023
Children's Health Ireland at Crumlin
2023
University of Liverpool
2015-2019
Ospedale Maggiore
2018
San Raffaele University of Rome
2018
Cystic Fibrosis Research Foundation
2006-2017
Background Chronic airway inflammation is the main driver of pathogenesis in respiratory diseases such as severe asthma, chronic obstructive pulmonary disease, cystic fibrosis (CF) and bronchiectasis. While role common pathogens widely recognised, influence other microbiota members still poorly understood. Methods We hypothesised that lung contains bacteria with immunomodulatory activity which modulate net levels immune activation by key pathogens. Therefore, we assessed effect several...
Cystic fibrosis (CF) airways disease represents an example of polymicrobial infection whereby different bacterial species can interact and influence each other. In CF patients Staphylococcus aureus is often the initial pathogen colonizing lungs during childhood, while Pseudomonas aeruginosa predominant isolated in adolescents adults. During chronic infection, P. undergoes adaptation to cope with antimicrobial therapy, host response co-infecting pathogens. However, S. co-exist same niche...
The opportunistic pathogen Pseudomonas aeruginosa is able to thrive in diverse ecological niches and cause serious human infection. P. environmental strains are producing various virulence factors that required for establishing acute infections several host organisms; however, the phenotypic variants favour long-term persistence cystic fibrosis (CF) airways. Whether strains, which have adapted CF-niche, lost their competitive fitness other environment remains be investigated. In this paper,...
Pseudomonas aeruginosa can establish life-long airways chronic infection in patients with cystic fibrosis (CF) pathogenic variants distinguished from initially acquired strain. Here, we analysed chemical and biological activity of P. Pathogen-Associated Molecular Patterns (PAMPs) clonal strains, including mucoid non-mucoid phenotypes, isolated during a period up to 7.5 years CF patient. Chemical structure by MS spectrometry defined lipopolysaccharide (LPS) lipid A peptidoglycan (PGN)...
ABSTRACT Azithromycin (AZM) ameliorates lung function in cystic fibrosis (CF) patients. This macrolide has been suggested to have anti-inflammatory properties as well other effects potentially relevant for therapy of CF. In this study, we utilized three CF (IB3-1, 16HBE14o- AS3, and 2CFSMEo-) two isogenic non-CF (C38 S1) airway epithelial cell lines investigate whether AZM could reduce tumor necrosis factor alpha (TNF-α) mRNA protein levels by real-time quantitative PCR analysis an...
Abstract Repeated cycles of infections, caused mainly by Pseudomonas aeruginosa, combined with a robust host immune response and tissue injury, determine the course outcome cystic fibrosis (CF) lung disease. As disease progresses, P. aeruginosa adapts to modifying dramatically its phenotype; however, it remains unclear whether how bacterial adaptive variants their persistence influence pathogenesis development. Using in vitro murine models infection, we showed that CF-adaptive shaped innate...
Mitochondrial therapy offers an alternative strategy for attenuation of hyperinflammation in cystic fibrosis lung disease.
CFTR modulators have been developed to correct and/or enhance activity in patients with specific cystic fibrosis (CF) genotypes. However, it is of great importance identify potential off-targets these novel therapies understand how they affect lung physiology CF.
Summary P seudomonas aeruginosa is a multi‐host opportunistic pathogen causing wide range of diseases because the armoury virulence factors it produces, and difficult to eradicate its intrinsic resistance antibiotics. Using an integrated whole‐genome approach, we searched for . genes with relevance. We constructed random library 57 360 Tn5 mutants in PAO1 ‐ L screened vitro those showing pleiotropic effects phenotypes (reduced swarming, exo‐protease pyocyanin production). A set these were...
Lung infection by Burkholderia species, in particular cenocepacia, accelerates tissue damage and increases post-lung transplant mortality cystic fibrosis patients. Host-microbe interplay largely depends on interactions between pathogen-specific molecules innate immune receptors such as Toll-like receptor 4 (TLR4), which recognizes the lipid A moiety of bacterial lipopolysaccharide (LPS). The human TLR4·myeloid differentiation factor 2 (MD-2) LPS complex is strongly activated hexa-acylated...
Abstract Resistance and tolerance mechanisms participate to the interplay between host pathogens. IL-17-mediated response has been shown be crucial for resistance respiratory infections, whereas its role in during chronic airway colonization is still unclear. Here, we investigated whether modulates of airways infection by P. aeruginosa . First, found that IL-17A levels were sustained mice at both early advanced stages confirmed these observations human samples from cystic fibrosis patients...
The opportunistic pathogen Pseudomonas aeruginosa can establish life-long chronic infections in the airways of cystic fibrosis (CF) patients. Persistent lifestyle is established with P. patho-adaptive variants, which are clonal initially-acquired strains. Several reports indicated that adapts by loss-of-function mutations enhance fitness CF and sustain its expansion during infection. To validate this model adaptation to identify novel genes involved microevolution, we designed a approach...
The clinical development of antibiotics with a new mode action combined efficient pulmonary drug delivery is priority against untreatable Pseudomonas aeruginosa lung infections. POL7001 macrocycle antibiotic belonging to the novel class protein epitope mimetic (PEM) molecules selective and potent activity P. We investigated ventilator-associated pneumonia (VAP) cystic fibrosis (CF) as indications potential treat MICs comparators were measured for reference strains. therapeutic efficacy given...
Staphylococcus aureus and Pseudomonas aeruginosa are key bacterial pathogens of the respiratory tract in patients with cystic fibrosis (CF). Although P. chronic bronchial infection is associated a poorer prognosis, consequences S. colonization on CF outcomes controversial.In this paper, murine models resembling traits human airways disease have been revisited using an schedule that mimics sequence events pulmonary patients. First, mice were infected aureus, embedded agar beads; was followed...
Chronic infection by Pseudomonas aeruginosa in cystic fibrosis (CF) patients is a major contributor to progressive lung damage and poorly treated available antibiotic therapy. An alternative approach the development of additional treatments identify complementary therapies which target bacterial virulence factors necessary for establishment and/or maintenance chronic infection. The P. elastase (LasB) has been suggested as an attractive anti-virulence due its extracellular location, harmful...
Pseudomonas aeruginosa is a common cause of healthcare-associated infections including pneumonia, bloodstream, urinary tract, and surgical site infections. The clinical outcome P. may be extremely variable among individuals at risk patients affected by cystic fibrosis. However, factors for infection remain largely unknown. To identify track the host influencing lung infections, inbred immunocompetent mouse strains were screened in pneumonia model system. A/J, BALB/cJ, BALB/cAnNCrl,...
Antibiotic discovery and preclinical testing are needed to combat the Pseudomonas aeruginosa health threat. Most frequently, antibiotic efficacy is tested in models of acute respiratory infection, with chronic pneumonia remaining largely unexplored. This approach generates serious concerns about evaluation treatment for chronically infected patients, highlights need animal that mimic course human disease. In this study, marketed antibacterial drugs tobramycin (TOB) colistin (COL) was murine...
Nontypeable Haemophilus influenzae (NTHi) is commonly isolated from airways of patients suffering chronic respiratory diseases, such as COPD or cystic fibrosis (CF). However, to what extent NTHi long-term infection contributes the lung inflammatory burden during airway disease still controversial. Here, we exploited human samples a small cohort CF and found that chronically infected with had significantly higher levels interleukin (IL)-8 CXCL1 than those who were not infected. To better...
Pseudomonas aeruginosa is an opportunistic pathogen and causes a wide range of acute chronic infections. P. infections are kept in check by effective immune surveillance the healthy host, while any imbalance or defect normal response can manifest disease. Invasive infection immunocompromised patients mediated potent extracellular cell bound bacterial virulence factors. Life‐threatening cystic fibrosis maintained pathogenic variants that contribute to evade detection clearance system. Here,...
Pulmonary infections caused by Mycobacterium abscessus (MA) have increased over recent decades, affecting individuals with underlying pathologies such as chronic obstructive pulmonary disease, bronchiectasis and, especially, cystic fibrosis. The lack of a representative and standardized model infection in mice has limited steps forward the field MA infection. To overcome this challenge, we refined method agar beads to establish immunocompetent mice. We evaluated bacterial count, lung...