- Tuberculosis Research and Epidemiology
- Mycobacterium research and diagnosis
- Quinazolinone synthesis and applications
- Immune Cell Function and Interaction
- Cytokine Signaling Pathways and Interactions
- Immune Response and Inflammation
- Infectious Diseases and Mycology
- Immunodeficiency and Autoimmune Disorders
- Diagnosis and treatment of tuberculosis
- Infectious Diseases and Tuberculosis
- Phenothiazines and Benzothiazines Synthesis and Activities
- Antibiotic Resistance in Bacteria
- Immune responses and vaccinations
- Cancer therapeutics and mechanisms
- SARS-CoV-2 and COVID-19 Research
- Monoclonal and Polyclonal Antibodies Research
- T-cell and B-cell Immunology
- Pneumocystis jirovecii pneumonia detection and treatment
- COVID-19 Clinical Research Studies
- Antibiotics Pharmacokinetics and Efficacy
- Pneumonia and Respiratory Infections
- Whipple's Disease and Interleukins
- Pharmacological Effects of Natural Compounds
- Bacterial Genetics and Biotechnology
- Microwave-Assisted Synthesis and Applications
Colorado State University
2014-2023
Urology Team
2020
Hospital de Egas Moniz
1998-2005
Instituto de Medicina Tropical
2004-2005
Universidade Nova de Lisboa
2001-2005
Nova Medical (United States)
2004
University of Lisbon
2004
University of London
1998-2001
London School of Hygiene & Tropical Medicine
1998-2001
Global spread of aggressive mycobacteria Many mycobacteria, in addition to those causing leprosy and tuberculosis, are capable infecting humans. Some can be particularly dangerous patients suffering from immunosuppression or chronic disease, such as cystic fibrosis (CF). Bryant et al. observed clusters near-identical isolates drug-resistant Mycobacterium abscessus reporting CF clinics. The similarity the suggests transmission between patients, rather than environmental acquisition. Although...
Azithromycin is a potent macrolide antibiotic with poorly understood antiinflammatory properties. Long-term use of azithromycin in patients chronic inflammatory lung diseases, such as cystic fibrosis (CF), results improved outcomes. Paradoxically, recent study reported that CF associated increased infection nontuberculous mycobacteria (NTM). Here, we confirm long-term by adults the development NTM, particularly multi-drug-resistant species Mycobacterium abscessus, and identify an underlying...
A vaccine with a four-protein fusion peptide from Mycobacterium tuberculosis effectively boosts the current childhood TB and protects against drug-resistant TB.
Jump starting pathogen evolution Mycobacteria are mostly environmental saprotrophs, but during human history, some have become our pathogens. In the past 50 years or so, intractable and virulent infections of Mycobacterium abscessus emerged in people with cystic fibrosis. Bryant et al. investigated how these mycobacteria evolved into pathogens so quickly (see Perspective by Brugha Spencer). Chronic lung offer plenty evolutionary scope for emergence clones after horizontal gene transfer...
The HN878 strain of Mycobacterium tuberculosis is regarded as "hypervirulent" due to its rapid growth and reduced survival infected mice when compared with other clinical isolates. This property has been ascribed an early increase in type I IFNs a failure generate TH1-mediated immunity, induced by response unusual cell wall phenolic glycolipid expressed the isolate. We show, however, that although IFN does play inhibitory role, this was most apparent during chronic disease stage common all...
ABSTRACT The phenothiazines chlorpromazine (CPZ) and thioridazine (TZ) have equal in vitro activities against antibiotic-sensitive -resistant Mycobacterium tuberculosis. These compounds not been used as anti- M. tuberculosis agents because their take place at concentrations which are beyond those that clinically achievable. In addition, chronic administration of CPZ produces frequent severe side effects. Because has shown to enhance the killing intracellular medium relevant, we investigated...
ABSTRACT Over the last 10 years, Mycobacterium abscessus group strains have emerged as important human pathogens, which are associated with significantly higher fatality rates than any other rapidly growing mycobacteria. These opportunistic pathogens widespread in environment and can cause a wide range of clinical diseases, including skin, soft tissue, central nervous system, disseminated infections; by far, most difficult to treat is pulmonary form. Infections M. often multidrug-resistant...
Expression of eight transporter genes Escherichia coli K-12 and its DeltaacrAB mutant prior to after induction both strains tetracycline resistance reversal induced were analyzed by quantitative reverse transcriptase PCR. All overexpressed with acrF being 80-fold more expressed in the tetracycline-induced strain.
In this study, we investigated the ability of four clinical isolates Mycobacterium tuberculosis representing a range virulence for their capacity to grow in bone marrow-derived macrophages. The rate growth each macrophages reflected known virulence, but most virulent strongly induced production cytokine tumor necrosis factor alpha. A key difference, however, was degree cell cytotoxicity observed with more strains after several days culture. Staining monolayers DNA fragmentation indicative...
Abstract Chronic lung disease as a result of Mycobacterium abscessus is an emerging infection in the United States. We characterized immune responses mice and guinea pigs infected with M. abscessus. C57BL/6 leptin-deficient ob/ob challenged low-dose aerosol (LDA) did not develop infection. However, when high-dose (HDA), developed established pulmonary response consisting early influx IFN-γ+ CD4+ T cells; this preceded successful clearance both strains mice, although mycobacterial elimination...
Cigarette smoke (CS) exposure is an epidemiological risk factor for tuberculosis, although the biological basis has not been elucidated.We exposed C57BL/6 mice to CS 14 weeks and examined their ability control aerosol infection of Mycobacterium tuberculosis Erdman.CS-exposed had more M. isolated from lungs spleens after 30 d, compared with mice. The CS-exposed worse lung lesions less splenic macrophages dendritic cells (DCs) producing interleukin12 tumor necrosis α (TNF-α). There were...
Abstract Pulmonary tuberculosis in guinea pigs is an extremely useful model for drug and vaccine testing due to the fact that its pathological disease process similar present humans. Progress this field has been hindered because tools necessary undertake a complete immunological analysis of pig cellular immune response against Mycobacterium have lacking. In study, we combined new flow cytometric gating strategy with immunohistochemistry track T cells, B MIL4 Ab, which detects both...
The bacterium Mycobacterium tuberculosis remains one of the world's most successful pathogens, a situation that is aggravated by fact existing vaccine, bovis BCG, not effective in adults. As with any purpose giving BCG vaccination to establish long-lived state memory immunity, but whether this successfully completely established still unclear. It generally accepted T cells can be divided into central and effector populations function phenotype; however, majority data supporting division have...
Nuclear factor-kappa B (NFκB) is a ubiquitous transcription factor that mediates pro-inflammatory responses required for host control of many microbial pathogens; on the other hand, NFκB has been implicated in pathogenesis inflammatory and infectious diseases. Mice with genetic disruption p50 subunit are more likely to succumb Mycobacterium tuberculosis (MTB). However, role defense humans not fully understood. We sought examine activation immune response human macrophages MTB. Targeted...
ABSTRACT The Beijing family of Mycobacterium tuberculosis strains is part lineage 2 (also known as the East Asian lineage). In clinical studies, we have observed that isolates from sublineage RD207 were more readily transmitted among humans. To investigate basis for this difference, tested representative with characteristic spoligotype four five sublineages in guinea pig model and subjected these to comparative whole-genome sequencing. results studies showed all capable growing causing lung...
BackgroundTuberculosis is one of the world's leading killers, stealing 1.4 million lives and causing 8.7 new relapsed infections in 2011. The only vaccine against tuberculosis BCG which demonstrates variable efficacy adults worldwide. Human infection with Mycobacterium results influx inflammatory cells to lung an attempt wall off bacilli by forming a granuloma. Gr1intCD11b+ are called myeloid-derived suppressor (MDSC) play major role regulation inflammation many pathological conditions....
The nontuberculous mycobacteria are a large group of acid-fast bacteria that very widely distributed in the environment. While Mycobacterium avium was once regarded as innocuous, its high frequency cause disseminated disease HIV-positive individuals illustrated potential pathogen. Much more recently, there is growing evidence incidence M. and related species increasing immunocompetent individuals. same has been observed for abscessus infections, which difficult to treat; accordingly, this...
Mycobacterium abscessus is a fast-growing, multidrug-resistant organism that has emerged as clinically significant pathogen in cystic fibrosis (CF) patients. The intrinsic resistance of M. to most commonly available antibiotics seriously restricts chemotherapeutic options. Herein, we report the potent activity series indolecarboxamides against abscessus. lead compounds, 6 and 12, exhibited strong vitro wide panel isolates infected macrophages. High levels appear be associated with an A309P...