The utility of pharmacokinetic studies for the evaluation of exposure-response relationships for standard dose anti-tuberculosis drugs
This article summarized the existing literature and their utility in evaluating the association between each anti-TB drug's concentrations using current target concentrations and treatment outcomes in patients with pulmonary tuberculosis receiving standard WHO-recommended dosing. (Source: Tuberculosis)
Source: Tuberculosis - November 7, 2017 Category: Respiratory Medicine Authors: Christine Sekaggya-Wiltshire, Mohammed Lamorde, Agnes N. Kiragga, Kelly E. Dooley, Moses R. Kamya, Andrew Kambugu, Jan Fehr, Yukari C. Manabe, Barbara Castelnuovo Tags: Review Source Type: research
The 7-phenyl benzoxaborole series is active against Mycobacterium tuberculosis
We identified a series of novel 7-phenyl benzoxaborole compounds with activity against Mycobacterium tuberculosis. Compounds had a range of activity with inhibitory concentrations (IC90) as low as 5.1 μM and no cytotoxicity against eukaryotic cells (IC50 > 50 μM). Compounds were active against intracellular mycobacteria cultured in THP-1 macrophages. We isolated and characterized resistant mutants with mutations in NADH dehydrogenase (Ndh) or the regulatory protein Mce3R. Mutations suggest that Ndh may be the target of this series. (Source: Tuberculosis)
Source: Tuberculosis - November 6, 2017 Category: Respiratory Medicine Authors: Aaron Korkegian, Theresa O'Malley, Yi Xia, Yasheen Zhou, David S. Carter, Bjorn Sunde, Lindsay Flint, Dean Thompson, Thomas R. Ioerger, Jim Sacchettini, M.R.K. Alley, Tanya Parish Source Type: research
Diagnostic performance of an optimized transcriptomic signature of risk of tuberculosis in cryopreserved peripheral blood mononuclear cells
A staggering 23% of the global population is estimated to be infected with Mycobacterium tuberculosis (M.tb) [1], representing an enormous reservoir of individuals at risk of progressing to active tuberculosis (TB) disease. Identification of those at risk of TB disease would allow targeted preventive therapy, potentially curtailing transmission [2]. We recently identified and validated a 16-gene whole blood transcriptomic correlate of risk (CoR) signature that can predict active TB disease in M.tb-infected individuals more than a year before disease manifestations and diagnosis [3]. (Source: Tuberculosis)
Source: Tuberculosis - November 6, 2017 Category: Respiratory Medicine Authors: Fatoumatta Darboe, Stanley Kimbung Mbandi, Ethan G. Thompson, Michelle Fisher, Miguel Rodo, Michele van Rooyen, Elizabeth Filander, Nicole Bilek, Simbarashe Mabwe, Mark Hatherill, Daniel E. Zak, Adam Penn-Nicholson, Thomas J. Scriba, The SATVI Clinical Im Source Type: research
A comparison of Rv0559c and Rv0560c expression in drug-resistant Mycobacterium tuberculosis in response to first-line antituberculosis drugs
Drug resistance to Mycobacterium tuberculosis is a major health problem worldwide. Mycobacterium tuberculosis can progress to be mono-drug resistant or multi-drug resistant by improper treatment. The chemical stress of M. tuberculosis was performed in this study. Rv0559c is an unknown secreted protein. Rv0560c is a putative benzoquinone methyltransferase of M. tuberculosis cell. Rv0559c gene is located downstream of Rv0560c gene. Both genes respond to salicylate stress. Drug susceptible, isoniazid resistant, rifampicin resistant and multi-drug resistant phenotypes of M. (Source: Tuberculosis)
Source: Tuberculosis - November 4, 2017 Category: Respiratory Medicine Authors: Ratikorn Gamngoen, Chanyanuch Putim, Parichat Salee, Ponrut Phunpae, Bordin Butr-Indr Source Type: research
IgG subclasses' response to a set of mycobacterial antigens in different stages of Mycobacterium tuberculosis infection
Despite the reported high heterogeneity of the human immune response to tuberculosis (TB), new studies may contribute to the understanding of Mycobacterium tuberculosis immunopathogenesis. To investigate the patterns of humoral response during latent (LTBI) and active TB, we evaluated specific IgG subclasses' response, by ELISA, to a set of mycobacterial antigens (Rv2029c, Rv2031c, Rv2034, Rv2628, Rv3353c ESAT6:CFP10, and the new chimeric PstS1(285-374):CFP10) in plasma samples from exposed uninfected controls (ExC, n = 24), LTBI (n = 61), and TB (n = 15) donors. (Source: Tuberculosis)
Source: Tuberculosis - October 31, 2017 Category: Respiratory Medicine Authors: Leonardo Silva de Araujo, Nidai de B árbara Moreira da Silva, Janaina Aparecida Medeiros Leung, Fernanda Carvalho Queiroz Mello, Maria Helena Féres Saad Tags: Immunological Aspects Source Type: research
An IclR like protein from mycobacteria regulates leuCD operon and induces dormancy-like growth arrest in Mycobacterium smegmatis
In this study, we identified an IclR like transcription regulator, Rv2989 involved in regulation of leuCD expression. Further, we have shown that the Rv2989 binding site overlaps with the promoter region of leuCD, indicating its direct involvement in the regulation of this operon. (Source: Tuberculosis)
Source: Tuberculosis - October 25, 2017 Category: Respiratory Medicine Authors: Rajendra Kumar Angara, Suhail Yousuf, Shailesh Kumar Gupta, Akash Ranjan Tags: Molecular Aspects Source Type: research
Screening of antitubercular compound library identifies novel ATP synthase inhibitors of Mycobacterium tuberculosis
In this study, inverted membrane vesicles of Mycobacterium smegmatis were prepared to establish luciferin based ATP estimation assay. This assay was used to screen 700 compounds which were earlier found to be active on the whole cell of M. (Source: Tuberculosis)
Source: Tuberculosis - October 25, 2017 Category: Respiratory Medicine Authors: Sunil Kumar, Rukmankesh Mehra, Sumit Sharma, Naveen Prakash Bokolia, Diksha Raina, Amit Nargotra, Parvinder Pal Singh, Inshad Ali Khan Tags: Drug Discovery and Resistance Source Type: research
I3-Ag85 effect on phthiodiolone dimycocerosate synthesis
The multiplicity of drug resistant Mycobacterium tuberculosis (Mtb) strains is a growing health issue. New therapies are needed, acting on new targets. The I3-Ag85 was already reported to reduce the amount of trehalose dimycolate lipid of the mycobacterial cell wall. This inhibitor of Ag85c increased the mycobacterial wall permeability. We previously showed that M. tuberculosis strains, even multi-drug resistant and extensively-drug resistant strains, can be susceptible to vancomycin when concomitantly treated with a drug altering the cell envelope integrity. (Source: Tuberculosis)
Source: Tuberculosis - October 23, 2017 Category: Respiratory Medicine Authors: C éline Rens, Françoise Laval, Ruddy Wattiez, Philippe Lefèvre, François Dufrasne, Mamadou Daffé, Véronique Fontaine Source Type: research
Editorial Board
(Source: Tuberculosis)
Source: Tuberculosis - October 17, 2017 Category: Respiratory Medicine Source Type: research
Investigating the inhibitory potential of 2-Aminopurine metal complexes against serine/threonine protein kinases from Mycobacterium tuberculosis
Tuberculosis – a disease caused by Mycobacterium tuberculosis (Mtb), is one of the most devastating. The discovery of Ser/Thr protein kinases (STPKs) in Mtb opened a new avenue for developing anti-tubercular inhibitors. The in-vivo inhibitory effects of many metal ions have been demonstrated in literature. But , one of the limitations of metal ions as inhibitors is their inability to traverse the hydrophobic membrane due to polar nature and their propensity for non-specific interactions. To overcome this, we attached a metal ion to 2-A9P – an analog derived from a cell permeable scaffold, 2-Aminopurine (2-AP) which is ...
Source: Tuberculosis - October 13, 2017 Category: Respiratory Medicine Authors: Vaibhav Singh Bais, Balaram Mohapatra, Nadim Ahamad, Sanjana Boggaram, Sandeep Verma, Balaji Prakash Source Type: research
Polymorphisms in Rv3806c (ubiA) and the upstream region of embA in relation to ethambutol resistance in clinical isolates of Mycobacterium tuberculosis from North India
Mutations at embB306 are the most prevalent polymorphisms associated with ethambutol (EMB) resistance, responsible for 40 –60% of EMB resistant clinical cases of tuberculosis (TB). The present study analyzed additional mutations associated with EMB resistance in the embB, embC, embA and Rv3806c (ubiA) genes in 29 EMB resistant and 29 EMB susceptible clinical isolates of M. tuberculosis selected from 360 patients with TB. The entire ubiA gene, mutational hotspot regions of embB, embC, and upstream region of embA were screened for polymorphisms by DNA sequencing and the results correlated with minimum inhibitory concentrat...
Source: Tuberculosis - October 11, 2017 Category: Respiratory Medicine Authors: Astha Giri, Shraddha Gupta, Hassan Safi, Anshika Narang, Kamal Shrivastava, Naresh Kumar, Subramanya Lingaraju, Mahmud Hanif, Anuj Bhatnagar, Balakrishnan Menon, David Alland, Mandira Varma-Basil Source Type: research
Impaired TNF, IL-1 β, and IL-17 production and increased susceptibility to Mycobacterium tuberculosis infection in HTLV-1 infected individuals
IFN- γ and TNF play critical roles in the control of Mycobacterium tuberculosis infection. Despite leading to an exaggerated production of inflammatory cytokines, HTLV-1 infection increases the risk of developing tuberculosis (TB). However, the immune mechanisms accounting for this phenomenon are still unclear. The aim of this study was to evaluate immunological aspects of the HTLV-1/M. tuberculosis co-infection. In this cross-sectional study, the levels of TNF, IL-1β, and IL-17 were determined by ELISA in the supernatants of either unstimulated or tuberculin purified protein derivative (PPD) sti mulated peripheral blood...
Source: Tuberculosis - October 9, 2017 Category: Respiratory Medicine Authors: Nat ália B. Carvalho, Maria de Lourdes Bastos, Anselmo S. Souza, Eduardo M. Netto, Sérgio Arruda, Silvane B. Santos, Edgar M. Carvalho Source Type: research
Assessment of tuberculosis contact investigation in Shanghai, China: An 8-year cohort study
Tuberculosis (TB) contact investigation has been observed as a useful programmatic tool in active case finding. We collected data of contact cases to evaluate the effectiveness of TB contact investigation programme in Shanghai, China. (Source: Tuberculosis)
Source: Tuberculosis - October 3, 2017 Category: Respiratory Medicine Authors: Qi Jiang, Liping Lu, Jie Wu, Chongguang Yang, Ravi Prakash, Tianyu Zuo, Qingyun Liu, Jianjun Hong, Xiaoqin Guo, Qian Gao Tags: Epidemiology Source Type: research
Distinct properties of a hypoxia specific paralog of single stranded DNA binding (SSB) protein in mycobacteria
In addition to the canonical Single Stranded DNA Binding (SSBa) protein, many bacterial species, including mycobacteria, have a paralogous SSBb. The SSBb proteins have not been well characterized. While in B. subtilis, SSBb has been shown to be involved in genetic recombination; in S. coelicolor it mediates chromosomal segregation during sporulation. Sequence analysis of SSBs from mycobacterial species suggests low conservation of SSBb proteins, as compared to the conservation of SSBa proteins. Like most bacterial SSB proteins, M. (Source: Tuberculosis)
Source: Tuberculosis - October 3, 2017 Category: Respiratory Medicine Authors: Amandeep Singh, M. Vijayan, Umesh Varshney Tags: Molecular Aspects Source Type: research
CISH controls bacterial burden early after infection with Mycobacterium tuberculosis in mice
CISH gene has been associated with increased susceptibility to human tuberculosis. We found that cish −/− mice had higher M. tuberculosis load in spleens and lungs up to 2.5 weeks after infection but not later compared to controls. Cish mRNA levels were increased in lungs at early and late time points after M. tuberculosis infection. In relation, the titers of inos and tnf mRNA in lungs were red uced early after infection of cish−/− mice.The transfer of cish−/− and control T cells conferred rag1−/− mice similar protection to infection with M. (Source: Tuberculosis)
Source: Tuberculosis - September 22, 2017 Category: Respiratory Medicine Authors: Berit Carow, Yu Gao, Graciela Ter án, Xuexian O. Yang, Chen Dong, Akihiko Yoshimura, Martin E. Rottenberg Tags: Immunological Aspects Source Type: research
