- Mycobacterium research and diagnosis
- Tuberculosis Research and Epidemiology
- Cystic Fibrosis Research Advances
- Infectious Diseases and Mycology
- Neutrophil, Myeloperoxidase and Oxidative Mechanisms
- Neonatal Respiratory Health Research
- Blood Pressure and Hypertension Studies
- Bacterial biofilms and quorum sensing
- Inhalation and Respiratory Drug Delivery
- Helicobacter pylori-related gastroenterology studies
- Gut microbiota and health
- Respiratory viral infections research
- Coral and Marine Ecosystems Studies
- Gastrointestinal Bleeding Diagnosis and Treatment
- Cardiac, Anesthesia and Surgical Outcomes
- Bacteriophages and microbial interactions
- Antibiotic Resistance in Bacteria
- Immune Response and Inflammation
- Blood properties and coagulation
- Advanced Nanomaterials in Catalysis
- Antimicrobial Peptides and Activities
- Marine and coastal plant biology
- Burkholderia infections and melioidosis
- Mental Health and Patient Involvement
- Advanced Chemical Sensor Technologies
National Jewish Health
2016-2025
University of Colorado Denver
2016-2025
University of Guayaquil
2020-2024
SUNY Downstate Health Sciences University
2024
State University of New York
2024
Kean University
2024
University of Limpopo
2018
Population Health Research Institute
2018
Hamilton Health Sciences
2018
McMaster University
2018
Two mycobacteriophages were administered intravenously to a male with treatment-refractory Mycobacterium abscessus pulmonary infection and severe cystic fibrosis lung disease. The phages engineered enhance their capacity lyse M. selected specifically as the most effective against subject's bacterial isolate. In setting of compassionate use, evidence phage-induced lysis was observed using molecular metabolic assays combined clinical assessments. isolates pre post-phage treatment demonstrated...
The inability of neutrophils to eradicate Pseudomonas aeruginosa within the cystic fibrosis (CF) airway eventually results in chronic infection by bacteria nearly 80 percent patients. Phagocytic killing P. CF is impaired due decreased transmembrane conductance regulator (CFTR) function and virulence factors acquired bacteria. Recently, neutrophil extracellular traps (NETs), structures composed chromatin complexed with granule contents, were identified as an alternative mechanism pathogen...
There is an urgent need to improve methods used screen antituberculosis drugs. An in vitro assay was developed test drug treatment strategies that specifically target drug-tolerant Mycobacterium tuberculosis. The H37Rv strain of M. tuberculosis survived antimicrobial as attached microbial communities when maintained tissue culture media (RPMI-1640) with or without lysed human peripheral blood leukocytes. When cultured planktonically the presence Tween-80, bacilli failed form reach...
Mycobacterium abscessus is a rapidly growing mycobacterium increasingly detected in the neutrophil-rich environment of inflamed tissues, including cystic fibrosis airway. Studies immune reaction to M. have focused primarily on macrophages and epithelial cells, but little known regarding neutrophil response despite predominantly neutrophillic inflammation typical these infections. In current study, human neutrophils released less superoxide anion than Staphylococcus aureus, pathogen that...
Rationale: Healthcare-associated transmission of nontuberculous mycobacteria (NTM) among people with cystic fibrosis (pwCF) has been investigated at CF centers worldwide, conflicting conclusions. We the Colorado Adult Program. Objectives: To systematically investigate healthcare-associated and/or acquisition NTM to determine similarity respiratory and environmental isolates, compare home residence watershed mapping pwCF having genetically similar isolates. Methods: Whole-genome sequencing...
Pseudomonas aeruginosa is a major pathogen in cystic fibrosis (CF) lung disease. Children with CF are routinely exposed to P. from the natural environment, and by adulthood, 80% of patients chronically infected. airway exhibits unique biofilm-like structure, where it grows small clusters or aggregates bacteria association abundant polymers neutrophil-derived components F-actin DNA, among other components. These differ substantially size appearance compared surface-attached vitro biofilm...
Pulmonary infections with Mycobacterium abscessus (M. abscessus) are increasingly prevalent in patients lung diseases such as cystic fibrosis. M. exists two morphotypes, smooth and rough, but the impact of morphotype on virulence is unclear. We developed an immune competent mouse model pulmonary infection tested differences host inflammatory response between morphotypes abscessus. Smooth rough were isolated from same American Type Culture Collection strain. Wild type fibrosis mice...
Rationale: Outbreaks of nontuberculous mycobacteria (NTM) among people with cystic fibrosis (pwCF) have been reported at CF centers conflicting conclusions. The occurrence NTM the UVMC (University Vermont Medical Center) adult program was investigated. Objectives: Use HALT (Healthcare-associated Links in Transmission NTM) toolkit to investigate healthcare-associated transmission and/or acquisition pwCF having genetically similar isolates. Methods: Whole genome sequencing isolates from 23...
Background Routine screening for nontuberculous mycobacterial (NTM) lung disease is dependent on sputum cultures. This particularly challenging in the cystic fibrosis (CF) population due to reduced production and low culture sensitivity. Biomarkers of infection that do not rely may lead earlier diagnosis, but validation trials require a unique prospective design. Purpose The rationale this trial investigate utility urine lipoarabinomannan (LAM) as test identify people with CF new positive...
Mycobacterium abscessus is a nontuberculous mycobacterium emerging as significant pathogen in individuals with chronic lung diseases, including cystic fibrosis and obstructive pulmonary disease. Current therapeutics have poor efficacy. Strategies of bacterial control based on host defenses are appealing; however, antimycobacterial immunity remains poorly understood further complicated by the appearance smooth rough morphotypes, which elicit distinct responses. We investigated role serum...
Bacteriophages (phages) are viruses that selectively infect bacteria and have been utilized to treat Mycobacterium abscessus (Mab) with varying success. The POSTSTAMP study is an ongoing, multi-site phage therapy protocol for treatment-refractory pulmonary Mab disease in people cystic fibrosis (pwCF). Participants (n = 10) prospectively assessed while utilizing FDA investigational new drug (IND) approval compassionate use. >6 years old, able produce sputum, treated guideline-based antibiotic...
Mycobacterium abscessus is a rapidly growing nontuberculous mycobacterium (NTM) increasingly reported in soft tissue infections and chronic lung diseases, including cystic fibrosis. The environmental source of M. has not been definitively identified, but NTM have detected soil water. To determine the potential soil-derived as an infectious source, we explored association, growth, survival with defined mineral particulates, kaolin, halloysite, silicone dioxide, house dust possible fomites....
Acute pulmonary exacerbations accelerate decline in cystic fibrosis (CF). There is a critical need for better predictors of treatment response.To test whether expression panel leucocyte genes directly measured from whole blood predicts reductions sputum bacterial density.A previously validated 10-gene peripheral mononuclear cell (PBMC) signature was prospectively tested PBMC and RNA isolated adult subjects with CF at the beginning end an acute exacerbation. Gene simultaneously quantified...
Mycobacterium abscessus, a rapidly growing nontuberculous mycobacterium, are increasingly present in soft tissue infections and chronic lung diseases, including cystic fibrosis, characterized by growth neutrophil-rich environments. M. abscessus is observed as two distinct smooth rough morphotypes. The environmental morphotype initiates infection has relatively limited ability to activate neutrophils. increased virulence immunogenicity. However, the neutrophil response not been explored....
Acute Respiratory Distress Syndrome (ARDS) severity may be influenced by heterogeneity of neutrophil activation. Interferon-stimulated genes (ISG) are a broad gene family induced Type I interferons, often as response to viral infections, which evokes extensive immunomodulation. We tested the hypothesis that over- or under-expression immunomodulatory ISG neutrophils is associated with worse clinical outcomes in patients ARDS. Genome-wide transcriptional profiles circulating isolated from...
BackgroundIndividuals with Cystic fibrosis (CF) are the most vulnerable population for pulmonary infection nontuberculous mycobacteria (NTM). Screening, diagnosis, and assessment of treatment response currently depend on traditional culture techniques, but sputum analysis NTM in CF is challenging, associated a low sensitivity. The cell wall lipoarabinomannan (LAM), lipoglycan found all mycobacterial species, has been validated as biomarker urine active Mycobacterium tuberculosis...
Mycobacterium abscessus, a rapidly growing nontuberculous mycobacterium, is increasingly prevalent in chronic lung disease, including cystic fibrosis, and infections are characterized by neutrophil-dominated environments. However, mechanisms of immune control poorly understood. Azithromycin, macrolide antibiotic with immunomodulatory effects, used to treat M. abscessus infections. Recently, inhibition macrophage bactericidal autophagy was described for azithromycin, which could be...
Background Healthcare-associated transmission of nontuberculous mycobacteria (NTM) among people with cystic fibrosis (pwCF) has been reported and is increasing concern. No standardized epidemiologic investigation tool published for healthcare-associated NTM outbreak investigations. This report describes the design an ongoing observational study to standardize approach pwCF. Methods a parallel multi-site pwCF within single Center who have respiratory isolates identified as being...
Abstract Pulmonary infections caused by mycobacteria cause significant mortality and morbidity in the human population. Diagnosing mycobacterial is challenging. An infection can lead to active disease or remain indolent with little clinical consequence. In patients pulmonary nontuberculosis (PNTM) identification of diagnosis take months years. Our previous studies showed potential diagnostic power volatile molecules exhaled breath samples detect M. tuberculosis infection. Herein, we...
Nontuberculous mycobacteria (NTM) infections are increasingly prevalent in chronic lung diseases, including cystic fibrosis (CF). Mycobacterium abscessus is of particular concern due to relatively greater virulence and intrinsic antimicrobial resistance. Airway culture identification, the standard method for detecting pulmonary infection, hindered by low sensitivity, long times, reliance on sputum production or lavage. A culture-independent test NTM infection could complement, replace,...
Nontuberculous mycobacteria (NTM), including Mycobacterium avium, are clinically important pathogens in cystic fibrosis (CF). The innate immune response to M. avium remains incompletely understood. We evaluated the role of complement opsonization neutrophil-mediated killing avium. Killing assays were performed using neutrophils from healthy donors (HDs) and persons with CF (pwCF). Clinical isolates opsonized plasma HDs or pwCF, which was intact heat-treated inactivate complement. HD had...