A5051498825- Mycobacterium research and diagnosis
- Tuberculosis Research and Epidemiology
- Bacterial biofilms and quorum sensing
- RNA and protein synthesis mechanisms
- Bacterial Genetics and Biotechnology
- RNA modifications and cancer
- Antibiotic Resistance in Bacteria
- Bacteriophages and microbial interactions
- Infectious Diseases and Tuberculosis
- Microbial Natural Products and Biosynthesis
- Pneumocystis jirovecii pneumonia detection and treatment
- Avian ecology and behavior
- Biochemical and Molecular Research
- Neutrophil, Myeloperoxidase and Oxidative Mechanisms
- Computational Drug Discovery Methods
- Cancer Research and Treatments
- Antimicrobial agents and applications
- Trace Elements in Health
- Microbial infections and disease research
- Heat shock proteins research
- Glycosylation and Glycoproteins Research
- Neonatal and fetal brain pathology
- Nanoparticles: synthesis and applications
- Advanced Neuroimaging Techniques and Applications
- Machine Learning in Materials Science
New York State Department of Health
2015-2024
Wadsworth Center
2015-2024
University at Albany, State University of New York
2017-2024
University of Pittsburgh
2008-2023
United States Department of State
2018
Indian Institute of Science Bangalore
2005
Centre for Cellular and Molecular Biology
2000-2001
Summary Successful treatment of human tuberculosis requires 6–9 months' therapy with multiple antibiotics. Incomplete clearance tubercle bacilli frequently results in disease relapse, presumably as a result reactivation persistent drug‐tolerant Mycobacterium cells, although the nature and location these persisters are not known. In other pathogens, antibiotic tolerance is often associated formation biofilms – organized communities surface‐attached cells but physiologically genetically...
Summary Many species of mycobacteria form structured biofilm communities at liquid–air interfaces and on solid surfaces. Full development Mycobacterium smegmatis biofilms requires addition supplemental iron above 1 μM ferrous sulphate, although is not needed for planktonic growth. Microarray analysis the M. transcriptome shows that iron‐responsive genes – especially those involved in siderophore synthesis uptake are strongly induced during formation reflecting a response to deprivation, even...
Mycobacterial species, like other microbes, spontaneously form multicellular drug-tolerant biofilms when grown in vitro detergent-free liquid media. The structure of Mycobacterium tuberculosis is formed through genetically programmed pathways and built upon a large abundance novel extracellular free mycolic acids (FM), although the mechanism FM synthesis remained unclear. Here we show that smegmatis produced enzymatic release from constitutively present mycolyl derivatives. One precursors...
ABSTRACT The chronic nature of tuberculosis (TB), its requirement long duration treatment, ability to evade immune intervention, and propensity relapse after drug treatment is discontinued are reminiscent other chronic, biofilm-associated bacterial diseases. Historically, Mycobacterium was grown as a pellicle, biofilm-like structure, at the liquid-air interface in variety synthetic media. Notably, most widely administered human vaccine, BCG, pellicle for vaccine production. However,...
Infections caused by biofilms are abundant and highly persistent, displaying phenotypic resistance to high concentrations of antimicrobials modulating host immune systems. Tuberculosis (TB), Mycobacterium tuberculosis, shares these qualities with biofilm infections. To identify genetic determinants formation in M. we performed a small-scale transposon screen using an vitro pellicle assay. We identified five tuberculosis mutants that were reproducibly attenuated for production relative the...
Significance Mycobacteria as well other bacteria remodel their ribosomes in response to zinc depletion by replacing zinc-binding ribosomal proteins with zinc-free paralogues, releasing for metabolic processes. In this study, we show that the remodeled ribosome acquires a structurally stable but functionally inactive and aminoglycoside-resistant state zinc-starved Mycobacterium smegmatis . Conversely, M. cells are growth arrested zinc-rich conditions have unstable reduced survival. We further...
Mycobacterium tuberculosis, the etiologic agent of human has an extraordinary ability to survive against environmental stresses including antibiotics. Although stress tolerance M. tuberculosis is one likely contributors 6-month long chemotherapy (1), molecular mechanisms underlying this characteristic phenotype pathogen remain unclear. Many microbial species have evolved in stressful environments by self-assembling highly organized, surface attached, and matrix encapsulated structures called...
Mycobacterium tuberculosis (Mtb) endures a combination of metal scarcity and toxicity throughout the human infection cycle, contributing to complex clinical manifestations. Pathogens counteract this paradoxical dysmetallostasis by producing specialized trafficking systems. Capture extracellular siderophores is widely accepted mode iron acquisition, Mtb iron-chelating siderophores, mycobactin, have been known since 1965. Currently, it not whether produces zinc scavenging molecules. Here, we...
Mycobacterium tuberculosis spontaneously grows at the air-medium interface, forming pellicle biofilms, which harbor more drug-tolerant persisters than planktonic cultures. The underlying basis for increased in M. biofilms is unknown. Using a transposon sequencing (Tn-seq) approach, we show here that multiple genes are necessary fitness of cells within but not cultures, also implicated tolerance bacilli to diverse set stressors and antibiotics. Thus, development appears be associated with an...
ABSTRACT Almost one-third of the world population today harbors tubercle bacillus asymptomatically. It is postulated that morphology and staining pattern long-term persistors are different from those actively growing culture. Interestingly, it has been found starved in vitro mycobacteria similar to obtained lung lesions. In order delineate biochemical characteristics mycobacteria, Mycobacteria smegmatis was grown 0.2% glucose as a sole carbon source along with an enriched culture 2% glucose....
Summary Most mycobacterial species spontaneously form biofilms, inducing unique growth physiologies and reducing drug sensitivity. Biofilm progresses through three genetically programmed stages: substratum attachment, intercellular aggregation architecture maturation. Growth of Mycobacterium smegmatis biofilms requires multiple factors including a chaperonin (GroEL1) nucleoid‐associated protein (Lsr2), although how their activities are linked remains unclear. Here it is shown that Lsr2...
The mycobacterial outer membrane, or mycomembrane, is essential for the viability and virulence of Mycobacterium tuberculosis related pathogens. mycomembrane a dynamic structure, whose chemical composition biophysical properties can change during stress to give an advantage bacterium. However, mechanisms that govern remodeling their significance pathogenesis are still not well characterized. Recent studies have shown trehalose dimycolate (TDM), major glycolipid broken down by...
Intrinsic and acquired antibiotic resistance in Mycobacterium abscessus presents challenges infection control, new therapeutic strategies are needed. Bacteriophage therapy shows promise, but variabilities M. phage susceptibility limits its broader utility. We show here that a mycobacteriophage-encoded lysin B (LysB) efficiently rapidly kills both smooth- rough-colony morphotype strains reduces the pulmonary bacterial load mice. LysB aerosolization plausible treatment for infections.
Significance We previously reported that hibernation of 70S ribosomes in mycobacteria is induced as a response to zinc starvation. Because limitation also induces ribosome remodeling, our findings raise questions about the conditions for remodeling and hibernation. Here, we show two processes are at different concentrations caseinolytic protease system plays crucial role zinc-dependent inhibition during remodeling. The offer insights into molecular pathway underlying transition from...