Pseudomonas aeruginosa senses and responds to epithelial potassium flux via Kdp operon to promote biofilm.

Mucosa-associated biofilms are associated with many human disease states, but the host mechanisms promoting biofilm remain unclear. In chronic respiratory diseases like cystic fibrosis (CF), Pseudomonas aeruginosa establishes chronic infection through biofilm formation. P.

Persistence and evolution of following initiation of highly effective modulator therapy in cystic fibrosis.

Unlabelled: Today, more than 90% of people with cystic fibrosis (pwCF) are eligible for the highly effective cystic fibrosis transmembrane conductance regulator (CFTR) modulator therapy called elexacaftor/tezacaftor/ivacaftor (ETI) and its use is widespread. Given the drastic respiratory symptom improvement experienced by many post-ETI, clinical studies are already underway to reduce the number of respiratory therapies, including antibiotic regimens, that pwCF historically relied on to combat lung disease progression. Early studies suggest that bacterial burden in the lungs is reduced post-ETI, yet it is unknown how chronic populations are impacted by ETI.

Effects of highly effective modulator therapy on the dynamics of the respiratory mucosal environment and inflammatory response in cystic fibrosis.

Background: While the widespread initiation of elexacaftor/tezacaftor/ivacaftor (ETI) has led to dramatic clinical improvements among persons with cystic fibrosis (pwCF), little is known about how ETI affects the respiratory mucosal inflammatory and physiochemical environment, or how these changes relate to lung function.

Methods: We performed a prospective, longitudinal study of adults with CF and chronic rhinosinusitis (CF-CRS) followed at our CF center (n = 18). Endoscopic upper respiratory tract (paranasal sinus) aspirates from multiple visit dates, both pre- and post-ETI initiation, were collected and tested for cytokines, metals, pH, and lactate levels.

Elexacaftor-tezacaftor-ivacaftor decreases pseudomonas abundance in the sinonasal microbiome in cystic fibrosis.

Background: Chronic rhinosinusitis (CRS) is common in individuals with cystic fibrosis (CF) and is marked by chronic inflammation and episodes of infection that negatively impact quality of life. Several studies have shown that elexacaftor-tezacaftor-ivacaftor (ETI) improves symptoms and examination findings in CF-CRS. The current study determines the effect of ETI on the sinonasal microbiota in CF.

Bacterial respiratory inhibition triggers dispersal of biofilms.

grows as a biofilm under many environmental conditions, and the bacterium can disperse from biofilms via highly regulated, dynamic processes. However, physiologic triggers of biofilm dispersal remain poorly understood. Based on prior literature describing dispersal triggered by forms of starvation, we tested bacterial respiratory inhibitors for biofilm dispersal in two models resembling chronic airway infections.

Iron bioavailability regulates Pseudomonas aeruginosa interspecies interactions through type VI secretion expression.

The cystic fibrosis (CF) respiratory tract harbors pathogenic bacteria that cause life-threatening chronic infections. Of these, Pseudomonas aeruginosa becomes increasingly dominant with age and is associated with worsening lung function and declining microbial diversity. We aimed to understand why P.

Elexacaftor-Tezacaftor- Ivacaftor improves sinonasal outcomes in cystic fibrosis.

Background: Many individuals with cystic fibrosis (CF) have chronic rhinosinusitis resulting in nasal obstruction, sinus infections, and repeated surgeries. Elexacaftor-tezacaftor-ivacaftor is a highly effective modulator therapy approved for individuals aged 6 years or older with CF who have at least one F508del allele or other responsive mutation. The current study tests the hypothesis that ELX/TEZ/IVA improves sinonasal disease in CF.

Successful treatment of refractory hypertension with bilateral nephrectomy in a patient with chronic kidney disease stage 3.

We present a case of life-threatening refractory hypertension (rHTN) in a patient with stage 3b chronic kidney disease that was unresponsive to open surgical renal denervation (RDN) but responded to bilateral nephrectomy (BLN). Both RDN and BLN reduce the increased sympathetic activation in rHTN. However, RDN has yet to show reductions in blood pressure adequate for the average patient with rHTN, and BLN has thus far been reserved for patients with preexisting end-stage kidney disease (ESKD).

Adaptation and genomic erosion in fragmented Pseudomonas aeruginosa populations in the sinuses of people with cystic fibrosis.

Pseudomonas aeruginosa notoriously adapts to the airways of people with cystic fibrosis (CF), yet how infection-site biogeography and associated evolutionary processes vary as lifelong infections progress remains unclear. Here we test the hypothesis that early adaptations promoting aggregation influence evolutionary-genetic trajectories by examining longitudinal P. aeruginosa from the sinuses of six adults with CF.

Antimicrobial Synergism Toward by Gallium(III) and Inorganic Nitrite.

The ubiquitous involvement of key iron-containing metalloenzymes in metabolism is reflected in the dependence of virtually all bacteria on iron for growth and, thereby, potentially provides multiple biomolecular targets for antimicrobial killing. We hypothesized that nitrosative stress, which induces damage to iron metalloproteins, would sensitize bacteria to the ferric iron mimic gallium(III) (Ga), potentially providing a novel therapeutic combination. Using both laboratory and clinical isolates of , we herein demonstrate that Ga and sodium nitrite synergistically inhibit bacterial growth under both aerobic and anaerobic conditions.

Dispersal of Epithelium-Associated Pseudomonas aeruginosa Biofilms.

grows in highly antibiotic-tolerant biofilms during chronic airway infections. Dispersal of bacteria from biofilms may restore antibiotic susceptibility or improve host clearance. We describe models to study biofilm dispersal in the nutritionally complex environment of the human airway.

Clinical predictors of cystic fibrosis chronic rhinosinusitis severity.

Background: Chronic rhinosinusitis (CRS) is a significant manifestation of cystic fibrosis (CF) with wide-ranging symptom and disease severity. The goal of the study was to determine clinical variables that correlate with outcome measures of disease severity.

Methods: A prospective, longitudinal, observational study of 33 adults with symptomatic CRS treated in a CF-focused otolaryngology clinic was performed.

NADH Dehydrogenases in Growth and Virulence.

is an opportunistic human pathogen with a complex respiratory chain. The bacterium is predicted to express three NADH:ubiquinone oxidoreductases (NDH-1, NDH-2 and Nqr). We created deletions strains of the predicted NADH:ubiquinone oxidoreductases alone, and in combination to determine the respective roles of the NADH dehydrogenases in growth and virulence.

Guillain-Barré syndrome hyponatremia: is it SIADH or pseudohyponatremia?

Approximately 5% of hospitalized patients with Guillain-Barré syndrome (GBS) experience SIADH; but pseudohyponatremia has also been reported in patients treated with IVIG. We present a case of a 51-year-old male with GBS who developed acute hyponatremia the day after initiation of IVIG; his sodium levels began to improve within 24 h of completion of IVIG. Differentiating between pseudohyponatremia caused by the IVIG treatment and SIADH caused by GBS was the key to successfully treating this patient.

Associations between heat exposure, vigilance, and balance performance in summer tree fruit harvesters.

Background: We sought to evaluate potential mediators of the relationship between heat exposure and traumatic injuries in outdoor agricultural workers.

Methods: Linear mixed models were used to estimate associations between maximum work-shift Wet Bulb Globe Temperature (WBGT) and post-shift vigilance (reaction time) and postural sway (total path length) in a cross-sectional sample of 46 Washington State tree fruit harvesters in August-September 2015.

Results: The mean (SD) WBGT was 27.

Sodium Nitrite Inhibits Killing of Pseudomonas aeruginosa Biofilms by Ciprofloxacin.

Sodium nitrite inhibits bacterial respiration and is in development as an antimicrobial for chronic bacterial infections associated with cystic fibrosis. The goal of the current study was to investigate the interaction between nitrite and ciprofloxacin. Using liquid culture killing assays and a biotic biofilm model, we observed that nitrite induces tolerance of ciprofloxacin.

Sodium nitrite blocks the activity of aminoglycosides against Pseudomonas aeruginosa biofilms.

Sodium nitrite has broad antimicrobial activity at pH 6.5, including the ability to prevent biofilm growth by Pseudomonas aeruginosa on the surfaces of airway epithelial cells. Because of its antimicrobial activity, nitrite is being investigated as an inhaled agent for chronic P.

Nitrite modulates bacterial antibiotic susceptibility and biofilm formation in association with airway epithelial cells.

Pseudomonas aeruginosa is the major pathogenic bacteria in cystic fibrosis and other forms of bronchiectasis. Growth in antibiotic-resistant biofilms contributes to the virulence of this organism. Sodium nitrite has antimicrobial properties and has been tolerated as a nebulized compound at high concentrations in human subjects with pulmonary hypertension; however, its effects have not been evaluated on biotic biofilms or in combination with other clinically useful antibiotics.

beta-Catenin is not necessary for maintenance or repair of the bronchiolar epithelium.

Signaling by Wnt/beta-catenin regulates self-renewal of tissue stem cells in the gut and, when activated in the embryonic bronchiolar epithelium, leads to stem cell expansion. We have used transgenic and cell type-specific knockout strategies to determine roles for beta-catenin-regulated gene expression in normal maintenance and repair of the bronchiolar epithelium. Analysis of TOPGal transgene activity detected beta-catenin signaling in the steady-state and repairing bronchiolar epithelium.