Evaluating the effects of ivacaftor exposure on small colony variant development and antibiotic tolerance.

Background: Ivacaftor exhibits anti-staphylococcal properties but does not clear from the lungs of people with cystic fibrosis (pwCF). We assessed whether exposure to therapeutic concentrations of ivacaftor could allow to form small colony variants (SCVs), a phenotype commonly associated with bacterial persistence.

Methods: Humanized G551D-CFTR (hG551D) rats were treated with ivacaftor for 7 days.

Temperature influences commensal-pathogen dynamics in a nasal epithelial cell co-culture model.

Chronic rhinosinusitis (CRS) is an inflammatory disease of the paranasal sinuses, and microbial dysbiosis associated with CRS is thought to be a key driver of host inflammation that contributes to disease progression. is a common upper respiratory tract (URT) pathobiont associated with higher carriage rates in CRS populations, where -secreted toxins can be identified in CRS tissues. Although many genera of bacteria colonize the URT, few account for the majority of sequencing reads.

Fibroblast Growth Factor 23 Signaling Does Not Increase Inflammation from Infection in the Cystic Fibrosis Bronchial Epithelium.

: Chronic inflammation due to (PA) infection in people with cystic fibrosis (CF) remains a concerning issue in the wake of modulator therapy initiation. Given the perpetuating cycle of colonization, infection, chronic inflammation, and recurrent injury to the lung, there are increases in the risk for mortality in the CF population. We have previously shown that fibroblast growth factor (FGF) 23 can exaggerate transforming growth factor (TGF) beta-mediated bronchial inflammation in CF.

A novel in vitro model to study prolonged Pseudomonas aeruginosa infection in the cystic fibrosis bronchial epithelium.

Pseudomonas aeruginosa (PA) is known to chronically infect airways of people with cystic fibrosis (CF) by early adulthood. PA infections can lead to increased airway inflammation and lung tissue damage, ultimately contributing to decreased lung function and quality of life. Existing models of PA infection in vitro commonly utilize 1-6-hour time courses.

secreted cytotoxins are competition sensing signals for .

Coinfection with two notorious opportunistic pathogens, the Gram-negative and Gram-positive , dominates chronic pulmonary infections. While coinfection is associated with poor patient outcomes, the interspecies interactions responsible for such decline remain unknown. Here, we dissected molecular mechanisms of interspecies sensing between and .

Acute Infection with a Tobramycin-Induced Small Colony Variant of Staphylococcus aureus Causes Increased Inflammation in the Cystic Fibrosis Rat Lung.

Cystic fibrosis (CF) disease is characterized by lifelong infections with pathogens such as Staphylococcus aureus, leading to eventual respiratory failure. Small colony variants (SCVs) of S. aureus have been linked to worse clinical outcomes for people with CF.

A genome-wide association study of severe asthma exacerbations in Latino children and adolescents.

Severe asthma exacerbations are a major cause of school absences and healthcare costs in children, particularly those in high-risk racial/ethnic groups.To identify susceptibility genes for severe asthma exacerbations in Latino children and adolescents, we conducted a meta-analysis of genome-wide association studies (GWAS) in 4010 Latino youth with asthma in four independent cohorts, including 1693 Puerto Ricans, 1019 Costa Ricans, 640 Mexicans, 256 Brazilians and 402 members of other Latino subgroups. We then conducted methylation quantitative trait locus, expression quantitative trait locus and expression quantitative trait methylation analyses to assess whether the top single nucleotide polymorphism (SNP) in the meta-analysis is linked to DNA methylation and gene expression in nasal (airway) epithelium in separate cohorts of Puerto Rican and Dutch children and adolescents.

Viral-Bacterial Co-infections in the Cystic Fibrosis Respiratory Tract.

A majority of the morbidity and mortality associated with the genetic disease Cystic Fibrosis (CF) is due to lung disease resulting from chronic respiratory infections. The CF airways become chronically colonized with bacteria in childhood, and over time commensal lung microbes are displaced by bacterial pathogens, leading to a decrease in microbial diversity that correlates with declining patient health. Infection with the pathogen is a major predictor of morbidity and mortality in CF, with CF individuals often becoming chronically colonized with in early adulthood and thereafter having an increased risk of hospitalization.

Biofilm Growth on Cystic Fibrosis Airway Epithelial Cells Is Enhanced during Respiratory Syncytial Virus Coinfection.

is a major cause of chronic respiratory infection in patients with cystic fibrosis (CF). We recently showed that exhibits enhanced biofilm formation during respiratory syncytial virus (RSV) coinfection on human CF airway epithelial cells (AECs). The impact of respiratory viruses on other bacterial pathogens during polymicrobial infections in CF remains largely unknown.

Simultaneous Antibiofilm and Antiviral Activities of an Engineered Antimicrobial Peptide during Virus-Bacterium Coinfection.

Antimicrobial-resistant infections are an urgent public health threat, and development of novel antimicrobial therapies has been painstakingly slow. Polymicrobial infections are increasingly recognized as a significant source of severe disease and also contribute to reduced susceptibility to antimicrobials. Chronic infections also are characterized by their ability to resist clearance, which is commonly linked to the development of biofilms that are notorious for antimicrobial resistance.

Development of an in vitro colonization model to investigate Staphylococcus aureus interactions with airway epithelia.

Staphylococcus aureus is a bacterial pathogen responsible for a wide range of diseases and is also a human commensal colonizing the upper respiratory tract. Strains belonging to the clonal complex group CC30 are associated with colonization, although the colonization state itself is not clearly defined. In this work, we developed a co-culture model with S.

Enterococcus faecalis 6-phosphogluconolactonase is required for both commensal and pathogenic interactions with Manduca sexta.

Enterococcus faecalis is a commensal and pathogen of humans and insects. In Manduca sexta, E. faecalis is an infrequent member of the commensal gut community, but its translocation to the hemocoel results in a commensal-to-pathogen switch.

Staphylococcus aureus Nuc2 is a functional, surface-attached extracellular nuclease.

Staphylococcus aureus is a prominent bacterial pathogen that causes a diverse range of acute and chronic infections. Recently, it has been demonstrated that the secreted nuclease (Nuc) enzyme is a virulence factor in multiple models of infection, and in vivo expression of nuc has facilitated the development of an infection imaging approach based on Nuc-activatable probes. Interestingly, S.

Quantification of confocal images of biofilms grown on irregular surfaces.

Bacterial biofilms grow on many types of surfaces, including flat surfaces such as glass and metal and irregular surfaces such as rocks, biological tissues and polymers. While laser scanning confocal microscopy can provide high-resolution images of biofilms grown on any surface, quantification of biofilm-associated bacteria is currently limited to bacteria grown on flat surfaces. This can limit researchers studying irregular surfaces to qualitative analysis or quantification of only the total bacteria in an image.

Staphylococcus aureus nuclease is an SaeRS-dependent virulence factor.

Several prominent bacterial pathogens secrete nuclease (Nuc) enzymes that have an important role in combating the host immune response. Early studies of Staphylococcus aureus Nuc attributed its regulation to the agr quorum-sensing system. However, recent microarray data have indicated that nuc is under the control of the SaeRS two-component system, which is a major regulator of S.

Reduced vancomycin susceptibility in an in vitro catheter-related biofilm model correlates with poor therapeutic outcomes in experimental endocarditis due to methicillin-resistant Staphylococcus aureus.

Staphylococcus aureus is the most common cause of endovascular infections, including catheter sepsis and infective endocarditis (IE). Vancomycin (VAN) is the primary choice for treatment of methicillin-resistant S. aureus (MRSA) infections.

New approaches for treating staphylococcal biofilm infections.

Bacteria of the genus Staphylococcus are a prominent cause of acute and chronic infections. The ability of the staphylococci to establish biofilms has been linked to the persistence of chronic infections, which has drawn considerable interest from researchers over the past decade. Biofilms can be defined as sessile communities of surface-attached cells encased in an extracellular matrix, and treatment of bacteria in this mode of growth is challenging due to the resistance of biofilm structures to both antimicrobials and host defenses.

Nuclease modulates biofilm formation in community-associated methicillin-resistant Staphylococcus aureus.

Community-associated methicillin-resistant Staphylococcus aureus (CA-MRSA) is an emerging contributor to biofilm-related infections. We recently reported that strains lacking sigma factor B (sigB) in the USA300 lineage of CA-MRSA are unable to develop a biofilm. Interestingly, when spent media from a USA300 sigB mutant was incubated with other S.