A5014160174- Tuberculosis Research and Epidemiology
- Mycobacterium research and diagnosis
- Infectious Diseases and Tuberculosis
- Antibiotic Resistance in Bacteria
- Vector-Borne Animal Diseases
- Immune responses and vaccinations
- Immune Response and Inflammation
- Immune Cell Function and Interaction
- Veterinary Oncology Research
- Pneumocystis jirovecii pneumonia detection and treatment
- COVID-19 Clinical Research Studies
- SARS-CoV-2 and COVID-19 Research
- Immunodeficiency and Autoimmune Disorders
- Animal Disease Management and Epidemiology
- Bacterial Infections and Vaccines
- Neuroinflammation and Neurodegeneration Mechanisms
- Infectious Diseases and Mycology
- Quinazolinone synthesis and applications
- vaccines and immunoinformatics approaches
- Diabetes and associated disorders
- Oral and Maxillofacial Pathology
- HIV Research and Treatment
- Advanced Glycation End Products research
- Pneumonia and Respiratory Infections
- Mosquito-borne diseases and control
Colorado State University
2016-2025
Protein Metrics (United States)
2024
Infectious Disease Research Institute
2022
University of Colorado Colorado Springs
2017
Abstract There is urgent need for new drug regimens that more rapidly cure tuberculosis (TB). Existing TB drugs and vary in treatment-shortening activity, but the molecular basis of these differences unclear, no existing assay directly quantifies ability a or regimen to shorten treatment. Here, we show historically classified as sterilizing non-sterilizing have distinct impacts on fundamental aspect Mycobacterium physiology: ribosomal RNA (rRNA) synthesis. In culture, mice, human studies,...
Multiple drug discovery initiatives for tuberculosis are currently ongoing to identify and develop new potent drugs with novel targets in order shorten treatment duration. One of the classes a mode action is DprE1 inhibitors targeting an essential process cell wall synthesis Mycobacterium tuberculosis. In this investigation, three clinical trials, TBA-7371, PBTZ169, OPC-167832, were evaluated side-by-side as single agents C3HeB/FeJ mouse model presenting caseous necrotic pulmonary lesions...
Tuberculosis lung lesions are complex and harbor heterogeneous microenvironments that influence antibiotic effectiveness. Major strides have been made recently in understanding drug pharmacokinetics pulmonary lesions, but the bacterial phenotypes arise under these conditions their contribution to tolerance poorly understood. A pharmacodynamic marker called RS ratio® quantifies ongoing rRNA synthesis based on abundance of newly synthesized precursor relative mature structural rRNA....
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...
Impaired glucose tolerance and type 2 diabetes were induced in guinea pigs to model the emerging comorbidity of Mycobacterium tuberculosis infection diabetic patients. Type mellitus was by low-dose streptozotocin rendered intolerant first feeding a high-fat, high-carbohydrate diet before M. exposure. resulted severe rapidly progressive (TB) with shortened survival interval, more pulmonary extrapulmonary pathology, higher bacterial burden compared glucose-intolerant nondiabetic controls....
Of the non-tuberculous mycobacteria, Mycobacterium abscessus is particularly refractory to antimicrobial therapy and new agents with activity against these pathogens are urgently needed. The screening of candidate M. requires a relevant reproducible animal model chronic infection. Granulocyte-macrophage colony-stimulating factor knockout (GM-CSF KO) mice were used develop pulmonary infection that can be for preclinical efficacy testing drugs. GM-CSF KO infected clinical isolate via...
Type 2 diabetes is a leading cause of morbidity and mortality among non-communicable diseases additional animal models that more closely replicate the pathogenesis human type are needed. The goal this study was to develop model in guinea pigs which diet-induced glucose intolerance precedes β cell cytotoxicity, two processes critical development diabetes. Guinea developed impaired tolerance after eight weeks feeding high fat, carbohydrate diet, as determined by oral challenge. Diet-induced...
Understanding the distribution patterns of antibiotics at site infection is paramount to selecting adequate drug regimens and developing new antibiotics. Tuberculosis (TB) lung lesions are made various immune cell types, some which harbor persistent forms pathogen, Mycobacterium tuberculosis. By combining high resolution MALDI MSI with histology staining quantitative image analysis in rabbits active TB, we have mapped a fluoroquinolone resolution, identified immune-pathological factors...
Mycobacterium tuberculosis HN878 represents a virulent clinical strain from the W-Beijing family, which has been tested in small animal models order to study its virulence and induction of host immune responses following infection. This isolate causes death extensive lung pathology infected C57BL/6 mice, whereas lab-adapted strains, such as M. H37Rv, do not. The use this clinically relevant increases possibilities assessing long-lived efficacy vaccines relatively inexpensive model. model...
A search for alternative Mycobacterium abscessus treatments led to our interest in the two-component regulator DosRS, which, tuberculosis , is required bacterium establish a state of nonreplicating, drug-tolerant persistence response variety host stresses. We show here that genetic disruption dosRS impairs adaptation M. hypoxia, resulting decreased bacterial survival after oxygen depletion, reduced tolerance number antibiotics vitro and vivo, inhibition biofilm formation. determined three...
ABSTRACT BTZ-043, a suicide inhibitor of the Mycobacterium tuberculosis cell wall synthesis decaprenylphosphoryl-beta- D -ribose 2′ epimerase, is under clinical development as potential new anti-tuberculosis agent. BTZ-043 potent and bactericidal in vitro but has limited activity against non-growing bacilli rabbit caseum. To better understand its behavior vivo , was evaluated for efficacy spatial drug distribution single agent C3HeB/FeJ mouse model presenting with caseous necrotic pulmonary...
Canine primary lung tumors typically appear radiographically as a well-circumscribed solitary mass in the periphery of caudal lobe. Consolidated and diffuse forms have also been described. Nineteen dogs with computed tomographic (CT) images thorax histological diagnosis tumor (17 carcinomas two sarcomas) were evaluated retrospectively to characterize CT findings. All bronchocentric origin internal air bronchograms. The bronchi narrowed, displaced, often obstructed by tumor. Eighteen 19 (95%)...
Hyperglycemia, the diagnostic feature of diabetes also occurs in non-diabetics associated with chronic inflammation and systemic insulin resistance. Since increased risk active TB diabetics has been linked to severity duration hyperglycemia, we investigated what effect diet-induced hyperglycemia had on Mycobacterium tuberculosis (Mtb) infection non-diabetic guinea pigs. Post-prandial was induced pigs normal chow by feeding a 40% sucrose solution daily or water as carrier control. Sucrose...
The expression of phenotypic drug resistance or tolerance serves as a strategy for Mycobacterium tuberculosis to survive in vivo antimicrobial treatment; however, the mechanisms are poorly understood. Progress toward more depth understanding and discovery new therapeutic strategies designed specifically treat drug-tolerant M. hampered by lack appropriate vitro assays. A library 2-aminoimidazole-based small molecules combined with antituberculosis isoniazid was screened against expressing...
Nontuberculous mycobacterial pulmonary disease (NTM-PD) is a potentially fatal infectious requiring long treatment duration with multiple antibiotics and against which there no reliable cure. Among the factors that have hampered development of adequate drug regimens lack an animal model reproduces NTM lung pathology required for studying antibiotic penetration efficacy. Given documented similarities between tuberculosis immunopathology in patients, we first determined rabbit active key...
Like other tuberculous and nontuberculous mycobacterial pathogens of human lung such as Mycobacterium tuberculosis M. abscessus, avium is likely exposed to a variety stressors during infection, including hypoxic conditions inside activated macrophages in the avascular necrotic regions granulomas. How survives stress establish chronic infection currently not well understood. Using RNA-sequencing, we here show that grown under progressive microaerophilic activates more than 4-fold subset 16...
Deer mice are the principal reservoir hosts of Sin Nombre virus, etiologic agent most hantavirus cardiopulmonary syndrome cases in North America. Infection deer results persistence without conspicuous pathology, and most, if not all, infected remain for life, with periods viral shedding. The kinetics load, histopathology, virus distribution, immune gene expression were examined. Viral antigen was detected as early 5 days postinfection peaked on day 15 lungs, hearts, kidneys, livers. RNA...
To date, most new vaccines against Mycobacterium tuberculosis, including recombinant versions of the current BCG vaccine, have usually been screened laboratory strains H37Rv or Erdman. In this study we took advantage our recent work in characterizing an increasingly large panel newly emerging clinical isolates [from United States from Western Cape region South Africa], to determine what extent would protect these [mostly high virulence] strains. We show here that both Pasteur and Aeras-422...
In the 1970s, inclusion of pyrazinamide (PZA) in drug regimen tuberculosis (TB) patients for first 2 mo achieved a drastic reduction therapy duration. Until now, however, mechanisms underlying PZA’s unique contribution to efficacy have remained controversial, and animal data vary across species. To understand how PZA kills bacterial populations present critical lung lesion compartments, we characterized rabbit model active TB, showing striking similarities types fates nonhuman primate models...
Although previous studies have shown that vitamin A deficiency is associated with incident tuberculosis (TB) disease, the direction of association has not been established. We investigated impact on TB disease progression.
The control of bacterial growth is key to the prevention and treatment tuberculosis (TB). Granulomas represent independent foci host immune response that present heterogeneous capacity for growth. At whole tissue level, B cells CD4 or CD8 T have an established role in protection against TB. Immune interact within each granuloma response, but impact composition on replication remains unknown. Here we investigate associations between cell composition, including cell, CD4, cells, state...
Abstract The nontuberculous mycobacteria (NTM) Mycobacterium avium is a clinically significant pathogen that can cause wide range of maladies, including tuberculosis-like pulmonary disease. An immunocompromised host status, either genetically or acutely acquired, presents large risk for progressive NTM infections. Due to this quietly emerging health threat, we evaluated the ability recombinant fusion protein ID91 combined with GLA-SE [ g lucopyranosyl l ipid djuvant, toll like receptor 4...