Role of glycans and glycoproteins in disease development by Mycobacterium tuberculosis.

School of Biotechnology, KIIT University, Bhubaneswar, Orissa, India.
Critical Reviews in Microbiology (Impact Factor: 6.09). 02/2012; 38(3):250-66. DOI: 10.3109/1040841X.2011.653550
Source: PubMed

ABSTRACT Glycoproteins play a critical role in host-pathogen interactions, antigenicity, and virulence determination, and are therefore, considered as potential drug targets. The cell wall of Mycobacterium tuberculosis (Mtb), the causative agent of tuberculosis (TB), dominantly contains sugars and lipids. Despite the efforts taken by the World Health Organization to reduce the incidence rate, the prevalence of TB is increasing in certain regions. This is mainly attributed to the emergence of multidrug-resistant bacteria. Factors that contribute to Mtb virulence and antigenicity remain elusive. However, several studies have shown that sugars and lipids are mainly responsible for Mtb pathogenesis and resistance to numerous drugs. This review gives insight into the role of glycoproteins in mycobacterium pathogenesis, disease development, and its implications in drug development.


Available from: Lakshmanan Jagannathan, Jun 15, 2015
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Artemisia nilagirica (Asteraceae) and Murraya koenigii (Rutaceae) are widely distributed in eastern region of India. Leaves of Artemisia nilagirica plant are used to treat cold and cough by the local tribal population in east India. Murraya koenigii is an edible plant previously reported to have an antibacterial activity. Pathogenic strains of mycobacteria are resistant to most of the conventional antibiotics. Therefore, it is imperative to identify novel antimycobacterial molecules to treat mycobacterial infection. In this study, ethanol, petroleum ether and water extracts of Artemisia nilagirica and Murraya koenigii were tested for antibacterial activity against Mycobacterium smegmatis and Mycobacterium bovis BCG in synergy with first line anti-tuberculosis (TB) drugs, and for cytotoxic activities on mouse macrophage RAW264.7 cells. Antibacterial activity was determined by colony forming unit (CFU) assay. Intracellular survival assay was performed by infecting RAW264.7 cells with M. smegmatis before and after treatment with plant extracts. Cytotoxity was checked by MTT [3-(4,5-Dimethylthiazol-2-yl)-2,5-Diphenyltetrazolium Bromide] assay. Genotoxicity was studied by DAPI staining and COMET assay using mouse macrophage RAW264.7 cell line. Cell apoptosis was checked by Annexin-V/FITC dual staining method. Reactive oxygen species and nitric oxide production was checked by DCFH staining and Griess reagent, respectively. Ethanol extracts of A. nilagirica (IC50 300 mug/ml) and M. koenigii (IC50 400 mug/ml) were found to be more effective against Mycobacterium smegmatis as compared to petroleum ether and water extracts. M. koenigii extract showed maximum activity against M. bovis BCG in combination with a first line anti-TB drug rifampicin. M. koenigii leaf extract also exerted more cytototoxic (IC50 20 mug/ml), genotoxic and apoptosis in mouse macrophage RAW 264.7 cell line. Treatment of mouse macrophages with A. nilagirica extract increased intracellular killing of M. smegmatis by inducing production of reactive oxygen species and nitric oxide. Ethanol extracts of A. nilagirica and M. koenigii were found to be more effective against mycobacteria. As compared to A. nilagirica, M. koenigii ethanol extract exhibited significant synergistic antibacterial activity against M. smegmatis and M. bovis BCG in combination with anti-tuberculosis drug rifampicin, and also showed increased cytotoxicity, DNA damage and apoptosis in mouse macrophages.
    BMC Complementary and Alternative Medicine 03/2014; 14(1):87. DOI:10.1186/1472-6882-14-87 · 1.88 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Tuberculosis (TB), an infectious disease caused by the pathogen Mycobacterium tuberculosis (Mtb), kills about 1.5 million people every year worldwide. An increase in the prevalence of drug-resistant strains of Mtb in the last few decades now necessitates the development of novel drugs that combat infections by both drug-sensitive and resistant Mtb. Moreover, as Mtb can persist in host cells by modulating their immune responses, it is essential that anti-TB agents be able to penetrate macrophages and kill the pathogen intracellularly without harming the host cells. In this context, antimicrobial peptides (AMPs) and proteins are being harnessed as anti-infective agents for the treatment of various diseases. Due to their direct and rapid bactericidal activity it is unlikely that pathogens acquire resistance against AMPs. Several short and potent AMP derivatives have been prepared by peptide engineering, and several of them are currently evaluated in clinical trials. The present review summarizes the role of endogenously expressed AMPs and proteins in the treatment of tuberculosis infections. In addition, mechanisms of direct anti-mycobacterial activity, manipulation of host immune responses, and future prospects of AMPs as therapeutic agents are discussed.
    Tuberculosis (Edinburgh, Scotland) 07/2014; 94(4). DOI:10.1016/ · 3.50 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Identification of reliable biomarkers for detection and staging of cancer and monitoring the outcome of anticancer therapy has been considered to be of high importance. We aimed to estimate the levels of serum glycoproteins, protein bound-hexose, protein bound hexosamine, protein bound fucose, protein bound sialic acid and protein bound carbohydrate in 32 ovarian cancer patients and compared them with the levels that found in 25 normal subjects. As compared to the normal subjects, all the four fractions of glycoproteins level were significantly elevated in ovarian cancer patients (p < 0.05). Chemotherapy in these patients significantly decreased the levels of serum glycoproteins (p < 0.05). Thus, high levels of serum glycoproteins in ovarian cancer patients could be due to abnormal protein glycosylation indicating malignant transformation of the cells.
    Indian Journal of Clinical Biochemistry 07/2014; 29(3). DOI:10.1007/s12291-013-0380-6