A5011238311- Cystic Fibrosis Research Advances
- Bacterial biofilms and quorum sensing
- Gut microbiota and health
- Tracheal and airway disorders
- Antibiotic Resistance in Bacteria
- Neonatal Respiratory Health Research
- Pediatric health and respiratory diseases
- Pneumonia and Respiratory Infections
- Respiratory viral infections research
- Child Nutrition and Feeding Issues
- Bacterial Genetics and Biotechnology
- Antimicrobial Resistance in Staphylococcus
- Dysphagia Assessment and Management
- Inhalation and Respiratory Drug Delivery
- Mycobacterium research and diagnosis
- Clostridium difficile and Clostridium perfringens research
- Vibrio bacteria research studies
- Cerebrospinal fluid and hydrocephalus
- Nematode management and characterization studies
- Congenital Diaphragmatic Hernia Studies
- Bacteriophages and microbial interactions
- Bacterial Infections and Vaccines
- Immune Response and Inflammation
- Pneumocystis jirovecii pneumonia detection and treatment
- interferon and immune responses
University of Washington
2016-2025
Seattle Children's Hospital
2016-2025
Seattle University
2005-2023
SleepMed
2023
Pulmonary Associates
2017-2022
Washington University in St. Louis
2021
University of British Columbia
2021
Southern California University for Professional Studies
2021
University of Southern California
2021
Infectious Disease Research Institute
2016
In many human infections, hosts and pathogens coexist for years or decades. Important examples include HIV, herpes viruses, tuberculosis, leprosy, malaria. With the exception of intensively studied viral infections such as HIV/AIDs, little is known about extent to which clonal expansion that occurs during long-term infection by involves important genetic adaptations. We report here a detailed, whole-genome analysis one infection, cystic fibrosis (CF) patient opportunistic bacterial pathogen...
Patients with cystic fibrosis periodically experience pulmonary exacerbations. Previous studies have noted that some patients' lung function (FEV(1)) does not improve treatment.To determine the proportion of patients treated for a exacerbation recover to spirometric baseline, and identify factors associated failure baseline.Cohort study using Cystic Fibrosis Foundation Patient Registry from 2003-2006. We randomly selected one intravenous antibiotics per patient compared best FEV(1) in 3...
Opportunistic infections are often polymicrobial. Two of the most important bacterial opportunistic pathogens humans, Pseudomonas aeruginosa and Staphylococcus aureus, frequently coisolated from catheters, endotracheal tubes, skin, eyes, respiratory tract, including airways people with cystic fibrosis (CF). Here, we show that suppression S. aureus respiration by a P. exoproduct, 4-hydroxy-2-heptylquinoline-N-oxide (HQNO), protects during coculture killing commonly used aminoglycoside...
Rationale: Previous work indicates that ivacaftor improves cystic fibrosis transmembrane conductance regulator (CFTR) activity and lung function in people with G551D-CFTR mutations but does not reduce density of bacteria or markers inflammation the airway. These findings raise possibility infection may progress independently CFTR once disease is established.Objectives: To better understand relationship between activity, airway microbiology inflammation, subjects chronic infections.Methods:...
Summary The opportunistic pathogen Pseudomonas aeruginosa undergoes genetic change during chronic airway infection of cystic fibrosis (CF) patients. One common is a mutation inactivating lasR , which encodes transcriptional regulator that responds to homoserine lactone signal activate expression acute virulence factors. Colonies mutants visibly accumulated the iridescent intercellular 4‐hydroxy‐2‐heptylquinoline. Using this colony phenotype, we identified P. emerged in CF patient early...
The bacterial second messenger cyclic diguanosine monophosphate (c-di-GMP) regulates cellular motility and the synthesis of organelles molecules that promote adhesion to a variety biological nonbiological surfaces. These properties likely require tight spatial temporal regulation c-di-GMP concentration. We have developed genetically encoded fluorescence resonance energy transfer (FRET)-based biosensors monitor concentrations within single cells by microscopy. Fluctuations were visualized in...
Chronic Pseudomonas aeruginosa infections cause significant morbidity in patients with cystic fibrosis (CF). Over years to decades, P. adapts genetically as it establishes chronic lung infections. Nonsynonymous mutations lasR, the quorum-sensing (QS) master regulator, are common CF. In laboratory strains of aeruginosa, LasR activates transcription dozens genes, including that for another QS RhlR. Despite frequency which lasR coding variants have been reported occur CF isolates, little is...
Chronic infection and concomitant airway inflammation is the leading cause of morbidity mortality for people living with cystic fibrosis (CF). Although chronic in CF undeniably polymicrobial, involving a lung microbiota, surveillance control approaches remain underpinned by classical aerobic culture-based microbiology. How to use microbiomics direct clinical management infections remains crucial challenge. A pivotal step towards leveraging microbiome care understand ecology identify...
The second messenger signaling molecule cyclic diguanylate monophosphate (c-di-GMP) drives the transition between planktonic and biofilm growth in many bacterial species. Pseudomonas aeruginosa has two surface sensing systems that produce c-di-GMP response to adherence. Current thinking field is once cells attach a surface, they uniformly respond by producing c-di-GMP. Here, we describe how Wsp system generates heterogeneity sensing, resulting physiologically distinct subpopulations of...
BACKGROUND. Lung infections are among the most consequential manifestations of cystic fibrosis (CF) and associated with reduced lung function shortened survival. Drugs called CFTR modulators improve activity dysfunctional transmembrane conductance regulator (CFTR) channels, which is physiological defect causing CF. However, it unclear how improved affects CF infections.
The cystic fibrosis (CF) modulator drug, elexacaftor/tezacaftor/ivacaftor (ETI), proved highly effective in controlled clinical trials for individuals with at least one F508del allele, which occurs 85% of people CF.
Background. Cystic fibrosis (CF) lung disease is associated with diverse bacteria chronically infecting the airways. Slow-growing, antibiotic-resistant mutants of Staphylococcus aureus known as small-colony variants (SCVs) have been isolated from respiratory secretions European adults and children CF using specific but infrequently used culture techniques. SCVs can be selected either by exposure to antibiotics or growth another pathogen, Pseudomonas aeruginosa. We sought determine...
Invasive methods requiring general anaesthesia are needed to sample the lung microbiota in young children who do not expectorate. This poses substantial challenges longitudinal study of paediatric airway microbiota. Non-invasive upper sampling is an alternative method for monitoring microbiota; however, there limited data describing relationship such results with children. In this study, we compared and lower determine whether non-invasive procedures provide a reliable measure either or...
<h3>Background</h3> Culture-independent analysis of the respiratory secretions people with cystic fibrosis (CF) has identified many bacterial species not previously detected using culture in this context. However, little is known about their clinical significance or persistence CF airways. <h3>Methods</h3> The authors characterised viable communities sputum collected from 14 patients at monthly intervals over 1 year a molecular community profiling technique—terminal restriction fragment...
Microbes are subjected to selective pressures during chronic infections of host tissues. Pseudomonas aeruginosa isolates with inactivating mutations in the transcriptional regulator LasR frequently selected within airways people cystic fibrosis (CF), and infection these has been associated poorer lung function outcomes. The mechanisms underlying selection for lasR mutation unknown but have postulated involve abundance specific nutrients CF airway secretions. We characterized mutant P....
Metagenomic sequencing is a promising approach for identifying and characterizing organisms their functional characteristics in complex, polymicrobial infections, such as airway infections people with cystic fibrosis. These analyses are often hampered, however, by overwhelming quantities of human DNA, yielding only small proportion microbial reads analysis. In addition, many abundant microbes respiratory samples can produce large extracellular bacterial DNA originating either from biofilms...
Abstract Rationale Lung function (FEV 1 ) generally improves during treatment of pulmonary exacerbations in patients with cystic fibrosis (CF). However, it is unclear how often return to previous baseline FEV achieved. Objectives (1) To determine the proportion pediatric CF treated for a exacerbation who fail recover and (2) identify factors associated this failure. Methods We performed case–control analysis from single center admitted their first 2001–2006. Patients were considered have...
Cystic fibrosis (CF) results in inflammation, malabsorption of fats and other nutrients, obstruction the gastrointestinal (GI) tract, yet mechanisms linking these disease manifestations to microbiome composition remain largely unexplored. Here we used metagenomic analysis systematically characterize fecal microbiomes children with without CF, demonstrating marked CF-associated taxonomic dysbiosis functional imbalance. We further showed that shifts were especially pronounced young CF...