A5083614231- Tuberculosis Research and Epidemiology
- Mycobacterium research and diagnosis
- Biochemical and Molecular Research
- Bacterial Genetics and Biotechnology
- Antibiotic Resistance in Bacteria
- Bacteriophages and microbial interactions
- Enzyme Structure and Function
- Microbial Natural Products and Biosynthesis
- Glycosylation and Glycoproteins Research
- Cancer therapeutics and mechanisms
- Enzyme Production and Characterization
- Genomics and Phylogenetic Studies
- RNA and protein synthesis mechanisms
- Infectious Disease Case Reports and Treatments
- Bacterial biofilms and quorum sensing
- Microbial Metabolic Engineering and Bioproduction
- Antimicrobial Resistance in Staphylococcus
- Microbial Metabolites in Food Biotechnology
- Carbohydrate Chemistry and Synthesis
- Nanoparticles: synthesis and applications
- Infectious Diseases and Tuberculosis
- Steroid Chemistry and Biochemistry
- Metallic Glasses and Amorphous Alloys
- Antimicrobial agents and applications
- Pneumocystis jirovecii pneumonia detection and treatment
Northumbria University
2015-2024
University of Birmingham
2002-2020
Applied Sciences (United States)
2008
Christ University
2005
Seiko Holdings (Japan)
2004
Newcastle University
1998-2002
University of Newcastle Australia
2001
University of Hull
1996-2000
Thioamide drugs, ethionamide (ETH) and prothionamide (PTH), are clinically effective in the treatment of Mycobacterium tuberculosis, M. leprae, avium complex infections. Although generally considered second-line drugs for their use has increased considerably as number multidrug resistant extensively drug tuberculosis cases continues to rise. Despite widespread thioamide treat leprosy, precise mechanisms action remain unknown. Using a cell-based activation method, we now have definitive...
ABSTRACT Many of the current antimycobacterial agents require some form cellular activation unmasking reactive groups, which in turn will bind to their specific targets. Therefore, understanding mechanisms antimycobacterials not only helps decipher drug resistance but may also facilitate development alternative strategies or analogues that do such processes. Herein, through use genetically defined strains Mycobacterium bovis BCG we provide evidence EthA, previously shown activate...
The Corynebacterianeae such as Corynebacterium glutamicum and Mycobacterium tuberculosis possess several unique structurally diverse lipids, including the genus-specific mycolic acids. Although function of a number genes involved in fatty acid biosynthesis is known, information relevant to initial steps within these biosynthetic pathways relatively sparse. Interestingly, genomes high accD genes, whose gene products resemble beta-subunit acetyl-CoA carboxylase Escherichia coli, providing...
The cell wall of <i>Mycobacterium tuberculosis</i> and related genera is unique among prokaryotes, consisting a covalently bound complex mycolic acids,d-arabinan d-galactan, which linked to peptidoglycan via special linkage unit Rha<i>p</i>-(1→3)-GlcNAc-P. Information concerning the biosynthesis this entire polymer now emerging with promise new drug targets against tuberculosis. Accordingly, we have developed galactosyltransferase assay that utilizes disaccharide neoglycolipid acceptors...
BackgroundMycolic acids are a complex mixture of branched, long-chain fatty acids, representing key components the highly hydrophobic mycobacterial cell wall. Pathogenic mycobacteria carry mycolic acid sub-types that contain cyclopropane rings. Double bonds at specific sites on precursors modified by action synthases (CMASs). The latter belong to family S-adenosyl-methionine-dependent methyl transferases, which several have been well studied in Mycobacterium tuberculosis, namely, MmaA1...
The suborder Corynebacterianeae comprises bacteria like Mycobacterium tuberculosis and Corynebacterium glutamicum, these contain in addition to the linear fatty acids, unique alpha-branched beta-hydroxy called mycolic acids. Whereas acetyl-coenzyme A (CoA) carboxylase activity is required provide malonyl-CoA for acid synthesis, a new type of apparently additionally present bacteria. It activates alpha-carbon by carboxylation, thus enabling its decarboxylative condensation with second afford...
Malonyl coenzyme A (CoA)-acyl carrier protein (ACP) transacylase (MCAT) is an essential enzyme in the biosynthesis of fatty acids all bacteria, including<i>Mycobacterium tuberculosis</i>. MCAT catalyzes transacylation malonate from malonyl-CoA to activated holo-ACP, generate malonyl-ACP, which elongation substrate acid biosynthesis. To clarify roles mycobacterial acyl (AcpM) and mycolic biosynthesis, we have cloned, expressed, purified <i>acpM</i> and<i>mtfabD</i> (malonyl-CoA:AcpM...
Mycolic acids consist of long-chain α-alkyl-β-hydroxy fatty that are produced by successive rounds elongation catalysed a type II acid synthase (FAS-II). A key feature in the process is condensation two-carbon unit from malonyl-acyl-carrier protein (ACP) to growing acyl-ACP chain β-ketoacyl-ACP (Kas). In present study, we provide evidence kasA Mycobacterium tuberculosis encodes an enzyme elongates vivo meromycolate chain, both smegmatis and chelonae. We demonstrate KasA belongs FAS-II...
Summary Lipooligosaccharides (LOSs) are antigenic glycolipids that present in some species of Mycobacterium including the Canetti strain M. tuberculosis . The core LOS structures from several mycobacterial organisms have been established, but biosynthetic pathways LOSs remain unknown. In this study, we describe two transposon insertion mutants marinum exhibit altered colony morphology. Cell wall analysis reveals MRS1271 mutant is defective synthesis LOS‐II, whereas MRS1178 accumulates an...
The low level of available iron in vivo is a major obstacle for microbial pathogens and stimulus the expression virulence genes. In this study, Mycobacterium tuberculosis H37Rv was grown aerobically presence limited availability chemostat culture to determine physiological response organism iron-limitation. A previously unidentified wax ester accumulated under iron-limited growth, changes abundance triacylglycerol menaquinone were also observed between iron-replete cultures. DNA microarray...
Flavonoids comprise a large group of bioactive polyphenolic plant secondary metabolites. Several these possess potent in vivo activity against Escherichia coli and Plasmodium falciparum, targeting enzymes involved fatty acid biosynthesis, such as enoyl-ACP-reductase, beta-ketoacyl-ACP reductase beta-hydroxyacyl-ACP dehydratase. Herein, we report that butein, isoliquirtigenin, 2,2',4'-trihydroxychalcone fisetin inhibit the growth Mycobacterium bovis BCG. Furthermore, vitro inhibition...
ABSTRACT Micrococcus luteus (NCTC2665, “Fleming strain”) has one of the smallest genomes free-living actinobacteria sequenced to date, comprising a single circular chromosome 2,501,097 bp (G+C content, 73%) predicted encode 2,403 proteins. The genome shows extensive synteny with that closely related organism, Kocuria rhizophila , from which it was taxonomically separated relatively recently. Despite its small size, harbors 73 insertion sequence (IS) elements, almost all are elements found in...
Aims: The antigen 85 complex (Ag85) from Mycobacterium tuberculosis consists of three abundantly secreted proteins (FbpA, FbpB and FbpC2) which play a key role in the pathogenesis also exhibit cell wall mycolyltransferase activity. A related protein with similarity to Ag85 was recently annotated M. genome as FbpC1. An investigation carried out determine whether FbpC1 may possess activity, characteristic feature complex. Methods Results: Heterologous expression FbpA, FbpC2 performed...
Mycobacterium tuberculosis PimB has been demonstrated to catalyze the addition of a mannose residue from GDP-mannose monoacylated phosphatidyl-myo-inositol mannoside (Ac(1)PIM(1)) generate Ac(1)PIM(2). Herein, we describe disruption its probable orthologue Cg-pimB and chemical analysis glycolipids lipoglycans isolated wild type Corynebacterium glutamicum C. glutamicum::pimB mutant. Following careful analysis, two related glycolipids, Gl-A Gl-X, were found in parent strain, but Gl-X was...
Isoniazid (INH) remains one of the key drugs used to control tuberculosis, with enoyl-AcpM reductase InhA being primary target. However, based on observation that INH-treated Mycobacterium tuberculosis overproduces KasA, an enzyme involved in biosynthesis mycolic acids, and induces formation a covalent complex consisting AcpM, INH, it has been proposed KasA represents target INH. relevance this INH action obscure. This study was aimed at clarifying role relation activity. By using anti-KasA...