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Mycobacterium tuberculosis

Anne Küntzel, Peter Oertel, Sina Fischer, Andreas Bergmann, Phillip Trefz, Jochen Schubert, Wolfram Miekisch, Petra Reinhold, Heike Köhler
BACKGROUND: Species of Mycobacteriaceae cause serious zoonotic diseases in mammals, for example tuberculosis in humans, dogs, parrots, and elephants (caused by Mycobacterium tuberculosis) and in ruminants and humans (caused by M. bovis and M. caprae). Pulmonary diseases, lymphadenitis, skin diseases, and disseminated diseases can be caused by non-tuberculous mycobacteria (NTM). Diagnosis and differentiation among Mycobacterium species are currently done by culture isolation. The established diagnostic protocols comprise several steps that allow species identification...
2018: PloS One
Malcolm Spain, Joseph K-H Wong, Gayathri Nagalingam, James M Batten, Elinor Hortle, Stefan Oehlers, Xiao Fan Jiang, Hasini E Murage, Jack T Orford, Patrick Crisologo, James A Triccas, Peter J Rutledge, Matthew H Todd
We recently reported the discovery of non-toxic cyclam-derived compounds that are active against drug-resistant Mycobacterium tuberculosis. In this paper we report exploration of the structure-activity relationship for this class of compounds, identifying several simpler compounds with comparable activity. The most promising compound identified, possessing significantly improved water solubility, displayed high levels of bacterial clearance in an in vivo zebrafish embryo model, suggesting this compound series has promise for in vivo treatment of tuberculosis...
March 20, 2018: Journal of Medicinal Chemistry
Caixia Hou, Tapan Biswas, Oleg Tsodikov
Bacterial primase DnaG is an essential nucleic acid polymerase that generates primers for replication of chromosomal DNA. The mechanism of DnaG remains unclear, due to the paucity of structural information on DnaG in complexes with other replisome components. Here we report the first crystal structures of noncovalent DnaG-DNA complexes, obtained with the RNA polymerase domain of Mycobacterium tuberculosis DnaG and various DNA ligands. One structure, obtained with ds DNA, reveals interactions with DnaG as it slides on ds DNA and suggests how DnaG binds template for primer synthesis...
March 20, 2018: Biochemistry
Kerri M Malone, Kévin Rue-Albrecht, David A Magee, Kevin Conlon, Olga T Schubert, Nicolas C Nalpas, John A Browne, Alicia Smyth, Eamonn Gormley, Ruedi Aebersold, David E MacHugh, Stephen V Gordon
Members of the Mycobacterium tuberculosis complex (MTBC) are the causative agents of tuberculosis in a range of mammals, including humans. A key feature of MTBC pathogens is their high degree of genetic identity yet distinct host tropism. Notably, while Mycobacterium bovis is highly virulent and pathogenic for cattle, the human pathogen M. tuberculosis is attenuated in cattle. Previous research also suggests that host preference amongst MTBC members has a basis in host innate immune responses. To explore MTBC host tropism, we present in-depth profiling of the MTBC reference strains M...
March 20, 2018: Microbial Genomics
Gurkamaljit Kaur, Bharati Pandey, Arbind Kumar, Naina Garewal, Abhinav Grover, Jagdeep Kaur
The lipolytic protein LipU was conserved in mycobacterium sp. including M. tuberculosis (MTB LipU) and M. leprae (MLP LipU). The MTB LipU was identified in extracellular fraction and was reported to be essential for the survival of mycobacterium. Therefore to address the problem of drug resistance in pathogen, LipU was selected as a drug target and the viability of finding out some FDA approved drugs as LipU inhibitors in both the cases was explored. Three dimensional (3D) model structures of MTB LipU and MLP LipU were generated and stabilized through molecular dynamics (MD)...
March 20, 2018: Journal of Biomolecular Structure & Dynamics
Basant Kumar, Vijai Dutta Upadhyaya, Sandeep Kumar Rahul, Laxmi Kant Bharti, Ram Nawal Rao, Sheo Kumar
Background: To analyse our experience with acute presentations of abdominal tuberculosis (TB) in children for early diagnosis and management. Materials and Methods: From December 2010 to April 2016, available electronic and operation theatre (OT) records of 17 patients with confirmed diagnosis of abdominal TB were analysed retrospectively. Parameters reviewed were age, sex, presentations, diagnostic investigations, surgery/intervention performed, final outcome and follow-up...
July 2017: African Journal of Paediatric Surgery: AJPS
Feng Su, Xin Chen, Xin Liu, Guanghui Liu, Yong Zhang
Bovine tuberculosis is a disease caused by Mycobacterium bovis (M. bovis) that leads to great economic losses in cattle production. The discovery of a reasonable bioagent to reduce M. bovis infection risk and environment contamination becomes significant and urgent. Previous study reported that human β-defensin-3 (HBD3) participated in Mycobacterial immunity and was recognized as a suitable candidate reagent. However, its minimal inhibitory concentration to M. bovis is not yet reported. In this study, we first purified HBD3 protein by recombinant-DNA technology and prokaryotic expression system...
March 20, 2018: AMB Express
Rachel E Bosserman, Cristal Reyna Thompson, Kathleen R Nicholson, Patricia A Champion
Mycobacterium marinum is a non-tuberculous pathogen of poikilothermic fish and an opportunistic human pathogen. Like tuberculous mycobacteria, the M. marinum M strain requires the ESX-1 (ESAT-6 System 1) secretion system for virulence in host cells. EsxB and EsxA, two major virulence factors exported by the ESX-1 system, are encoded by the esxBA genes within the ESX-1 locus. Deletion of the esxBA genes abrogates ESX-1 export and attenuates M. marinum in ex vivo and in vivo models of infection. Interestingly, there are several duplications of the esxB and esxA genes ( esxB_1, esxB_2, esxA_1 , esxA_2, and esxA_3 ) in the M...
March 19, 2018: Journal of Bacteriology
Tian Shen, Xingjian Cao, Junwei Shi, Yu Yu, Yihua Zhu, Delin Gu
BACKGROUND: Monocytes play a crucial role in immune response against Mycobacterium tuberculosis infection. The purpose of this current study was to investigate the morphology present on monocytes in peripheral blood from patients with active pulmonary tuberculosis (APTB) and the laboratory performance of the changes for discriminating cases from normal healthy subjects (NHS). METHOD: A total of 71 peripheral blood samples from patients with APTB, and 65 samples from NHS were analyzed...
March 16, 2018: Clinica Chimica Acta; International Journal of Clinical Chemistry
Xue-Juan Bai, Hong-Min Li, You-Rong Yang, Jun-Xian Zhang, Yan Liang, Xue-Qiong Wu
Relapse of pulmonary tuberculosis (PTB) is associated with a failure of the host immune system to control the invading Mycobacterium tuberculosis. Severe immunodeficiency or immune disorders may be the main reason for TB recurrence. This study aimed to quantify serum inflammatory cytokine and soluble adhesion molecule levels in Re-treated smear-positive PTB patients before and after re-anti-TB drug therapy. Serum samples were collected from 30 healthy controls and 215 Treated active PTB patients at baseline and 2, 4, and 6 months post-re-treatment...
March 16, 2018: Cytokine
Anneliese S Ashhurst, Thaigarajan Parumasivam, John Gar Yan Chan, Leon C W Lin, Manuela Flórido, Nicholas P West, Hak-Kim Chan, Warwick J Britton
Tuberculosis places a staggering burden on human health globally. The new World Health Organisation End-TB Strategy has highlighted the urgent need for more effective TB vaccines to improve control of the disease. Protein-based subunit vaccines offer potential as safe and effective generators of protective immunity, and the use of particulate vaccine formulation and delivery by the pulmonary route may enhance local immunogenicity. In this study, novel particulate subunit vaccines were developed utilising biodegradable poly(lactic-co-glycolic acid) (PLGA) slow-release particles as carriers for the Mycobacterium tuberculosis lipoprotein MPT83, together with the adjuvants trehalose-dibehenate (TDB) or Monophosphoryl lipid A (MPL)...
2018: PloS One
Liming Wang, Herman S Overkleeft, Gijsbert A van der Marel, Jeroen D C Codée
The development of a general glycosylation method that allows for the stereoselective construction of glycosidic linkages is a tremendous challenge. Because of the differences in steric and electronic properties of the building blocks used the outcome of a glycosylation reaction can greatly vary when switching form one glycosyl donor-acceptor pair to another. We here report a strategy to install cis-glucosidic linkages in a fully stereoselective fashion that is under direct control of the reagents used to activate a singly type of donor building block...
March 19, 2018: Journal of the American Chemical Society
Riti Sharan, Hee-Jeong Yang, Preeti Sule, Jeffrey D Cirillo
Reporter enzyme fluorescence (REF) utilizes substrates that are specific for enzymes present in target organisms of interest for imaging or detection by fluorescence or bioluminescence. We utilize BlaC, an enzyme expressed constitutively by all M. tuberculosis strains. REF allows rapid quantification of bacteria in lungs of infected mice. The same group of mice can be imaged at many time points, greatly reducing costs, enumerating bacteria more quickly, allowing novel observations in host-pathogen interactions, and increasing statistical power, since more animals per group are readily maintained...
February 26, 2018: Journal of Visualized Experiments: JoVE
Kirstin Harling, Ernest Adankwah, Alptekin Güler, Anthony Afum-Adjei Awuah, Louis Adu-Amoah, Ertan Mayatepek, Ellis Owusu-Dabo, Norman Nausch, Marc Jacobsen
T-cells critically contribute to protection against Mycobacterium tuberculosis infection, and impaired T-cell responses can lead to disease progression. Pro-inflammatory and immunosuppressive cytokines affect T-cells, and fine-tuned regulation of cytokine signaling via the Jak/STAT signaling pathways is crucial for appropriate T-cell function. Constitutive STAT3 phosphorylation as a consequence of aberrant cytokine signaling has been described to occur in pathognomonic T-cell responses in inflammatory and autoimmune diseases...
March 19, 2018: Cellular & Molecular Immunology
Jale Moradi, Maryam Izad, Mina Tabrizi, Nader Mosavari, Behnaz Esmaeili, Mohammad Mehdi Feizabadi
One third of the world population are latently infected with Mycobacterium tuberculosis and are at the risk of reactivation of tuberculosis (TB). The most effective strategy for control of TB worldwide is the development of a vaccine that inhibits progression of latent TB to active infection. In this study, two optimized constructs consisting of multi-epitopes DNA derived from three latency antigens Rv2029c, Rv2031c, and Rv2627c fused with or without light chain 3 (LC3) are synthetized. The immunogenicity effectiveness of two DNA constructs was evaluated in the mouse model...
March 19, 2018: Acta Microbiologica et Immunologica Hungarica
Shalini, Albertus Viljoen, Laurent Kremer, Vipan Kumar
The success in exploring anti-tubercular potency of nitroimidazole and quinoline, the core moieties of recently approved anti-tubercular drugs instigated us to synthesize a series of alkylated/aminated 2-methyl-5-nitroimidazoles and nitroimidazole-7-chloroquinoline conjugates and to evaluate them for their activities against Mycobacterium tuberculosis as well as for their cytotoxicity towards the J774 murine macrophage cell line. Although the synthesized compounds did not surpass the activity of the standard drug Isoniazid, they have appreciable activities with minimal cytotoxicity...
March 8, 2018: Bioorganic & Medicinal Chemistry Letters
Jana Amlerova, Ibrahim Bitar, Jaroslav Hrabak
Tuberculosis (TB) is considered one of the most serious infectious diseases worldwide. Effective control of tuberculosis infection involves multiple steps, such as reliable detection, treatment, an epidemiological control as a part of case management, and further surveillance and monitoring of TB spread in the human population. Due to the accelerating advances in molecular biology, especially in DNA sequencing, in the past decade, the application of these methods has become crucial for TB evolution studies, differentiation of Mycobacterium tuberculosis genotypes, and their distribution...
March 17, 2018: Folia Microbiologica
Cristian Alfredo Segura-Cerda, Michel de Jesús Aceves-Sánchez, Brenda Marquina-Castillo, Dulce Mata-Espinoza, Jorge Barrios-Payán, Perla Jazmín Vega-Domínguez, César Pedroza-Roldán, Jorge Bravo-Madrigal, Alba Adriana Vallejo-Cardona, Rogelio Hernández-Pando, Mario Alberto Flores-Valdez
Pellicles, a type of biofilm, have gathered a renewed interest in the field of tuberculosis as a structure that mimics some characteristics occurring during M. tuberculosis infection, such as antibiotic recalcitrance and chronicity of infection, and as a source of antigens for humoral response in infected guinea pigs. In other bacteria, it has been well documented that the second messenger c-di-GMP modulates the transition from planktonic cells to biofilm formation. In this work, we used the live vaccine Mycobacterium bovis BCG to determine whether deletion of genes involved in c-di-GMP metabolism would affect interaction with macrophages, capacity to induce immune response in a murine cell line and mice, and how the protein profile was modified when grown as surface pellicles...
March 14, 2018: Vaccine
André Campaniço, Rui Moreira, Francisca Lopes
Tuberculosis (TB) remains a major health problem worldwide. The infectious agent, Mycobacterium tuberculosis, has a unique ability to survive within the host, alternating between active and latent disease states, and escaping the immune system defences. The extended duration of anti-TB regimens and the increasing prevalence of multidrug- (MDR) and extensively drug-resistant (XDR) M. tuberculosis strains have created an urgent need for new antibiotics active against drug-resistant organisms and that can shorten standard therapy...
March 9, 2018: European Journal of Medicinal Chemistry
R J Orton, M Deason, P R Bessell, D M Green, R R Kao, L C M Salvador
Bovine tuberculosis (bTB) is a chronic zoonosis with major health and economic impact on the cattle industry. Despite extensive control measures in cattle and culling trials in wildlife, the reasons behind the expansion of areas with high incidence of bTB breakdowns in Great Britain remain unexplained. By balancing the importance of cattle movements and local transmission on the observed pattern of cattle outbreaks, we identify areas at elevated risk of infection from specific Mycobacterium bovis genotypes...
March 1, 2018: Epidemics
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