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Matthew B McNeil, Devon Dennison, Catherine Shelton, Lindsay Flint, Aaron Korkegian, Tanya Parish
No abstract text is available yet for this article.
February 8, 2018: Tuberculosis
Stephanie A Harris, Andrew White, Lisa Stockdale, Rachel Tanner, Laura Sibley, Charlotte Sarfas, Joel Meyer, Jonathan Peter, Matthew K O'Shea, Zita-Rose Manjaly Thomas, Ali Hamidi, Iman Satti, Mike J Dennis, Helen McShane, Sally Sharpe
The lack of validated immunological correlates of protection makes tuberculosis vaccine development difficult and expensive. Using intradermal bacille Calmette-Guréin (BCG) as a surrogate for aerosol Mycobacterium tuberculosis (M.tb) in a controlled human infection model could facilitate vaccine development, but such a model requires preclinical validation. Non-human primates (NHPs) may provide the best model in which to do this. Cynomolgus and rhesus macaques were infected with BCG by intradermal injection...
January 2018: Tuberculosis
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
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...
January 2018: Tuberculosis
Céline Rens, Françoise Laval, Ruddy Wattiez, Philippe Lefèvre, François Dufrasne, Mamadou Daffé, Véronique Fontaine
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...
January 2018: Tuberculosis
Rajendra Kumar Angara, Suhail Yousuf, Shailesh Kumar Gupta, Akash Ranjan
leuCD operon encodes isopropylmalate isomerase (IPMI), an essential enzyme in leucine biosynthesis. Leucine biosynthesis is one of the essential metabolic pathways for Mycobacterium tuberculosis survival inside the macrophage. 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. Ectopic expression of Rv2989 in M...
January 2018: Tuberculosis
Christine Sekaggya-Wiltshire, Mohammed Lamorde, Agnes N Kiragga, Kelly E Dooley, Moses R Kamya, Andrew Kambugu, Jan Fehr, Yukari C Manabe, Barbara Castelnuovo
Tuberculosis (TB) is a major public health problem. Many countries still fall below the minimum World Health Organization (WHO) TB treatment target success rate. There is conflicting evidence about whether concentrations of anti-tuberculosis drugs given at standard doses have an effect on treatment outcomes. The current data correlating anti-TB drug concentrations and treatment outcome is limited. 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...
January 2018: Tuberculosis
Leonardo Silva de Araujo, Nidai de Bárbara Moreira da Silva, Janaina Aparecida Medeiros Leung, Fernanda Carvalho Queiroz Mello, Maria Helena Féres Saad
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...
January 2018: Tuberculosis
Ratikorn Gamngoen, Chanyanuch Putim, Parichat Salee, Ponrut Phunpae, Bordin Butr-Indr
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...
January 2018: Tuberculosis
Sunil Kumar, Rukmankesh Mehra, Sumit Sharma, Naveen Prakash Bokolia, Diksha Raina, Amit Nargotra, Parvinder Pal Singh, Inshad Ali Khan
A limited number of anti-tuberculosis drug candidates with novel mode of action have entered clinical trials in recent years. ATP synthase is one such validated drug target which has yielded a drug recently. The aim of this study was to identify the novel chemical scaffolds targeting the Mycobacterium tuberculosis (M. tuberculosis) ATP synthase. 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...
January 2018: Tuberculosis
Vaibhav Singh Bais, Balaram Mohapatra, Nadim Ahamad, Sanjana Boggaram, Sandeep Verma, Balaji Prakash
Tuberculosis - a disease caused by Mycobacterium tuberculosis (Mtb), is one of the most devastating disease. 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 a known kinase inhibitor...
January 2018: Tuberculosis
Astha Giri, Shraddha Gupta, Hassan Safi, Anshika Narang, Kamal Shrivastava, Naresh Kumar Sharma, Subramanya Lingaraju, Mahmud Hanif, Anuj Bhatnagar, Balakrishnan Menon, David Alland, Mandira Varma-Basil
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 concentrations (MIC) of EMB...
January 2018: Tuberculosis
Natália B Carvalho, Maria de Lourdes Bastos, Anselmo S Souza, Eduardo M Netto, Sérgio Arruda, Silvane B Santos, Edgar M Carvalho
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) stimulated peripheral blood mononuclear cells...
January 2018: Tuberculosis
Chong Wang, Su Yang, Chang-Ming Liu, Ting-Ting Jiang, Zhong-Liang Chen, Hui-Hui Tu, Lian-Gen Mao, Zhong-Jie Li, Ji-Cheng Li
Rapid and efficient methods for the determination of cured pulmonary tuberculosis (TB) are lacking. We screened serum miRNAs using the Solexa sequencing method among untreated TB patients, two-month treated TB patients, cured TB patients, and healthy controls. A total of 100 differentially expressed miRNAs were identified in cured TB patients, including 37 up-regulated (fold change >1.50, P < 0.05) and 63 down-regulated (fold change <0.60, P < 0.05) miRNAs. Gene ontology (GO) enrichment analysis revealed that most of the predicted genes were present in the nucleus with a strong protein binding function...
January 2018: Tuberculosis
Raju Botta, Pongpan Chindaudom, Pitak Eiamchai, Mati Horprathum, Saksorn Limwichean, Chanunthorn Chananonnawathorn, Viyapol Patthanasettakul, Benjawan Kaewseekhao, Kiatichai Faksri, Noppadon Nuntawong
Nanostructures have been multiplying the advantages of Raman spectroscopy and further amplify the advantages of Raman spectroscopy is a continuous effort focused on the appropriate design of nanostructures. Herein, we designed different shapes of plasmonic nanostructures such as Vertical, Zig Zag, Slant nanorods and Spherical nanoparticles employing the DC magnetron sputtering system as SERS-active substrates for ultrasensitive detection of target molecules. The fabricated plasmonic nanostructures sensitivity and uniformity were exploited by reference dye analyte...
January 2018: Tuberculosis
Mamoru Fujiwara, Masanori Kawasaki, Norimitsu Hariguchi, Yongge Liu, Makoto Matsumoto
Delamanid, a bicyclic nitroimidazooxazole, is effective against M. tuberculosis. Previous studies have shown that resistance to a bicyclic nitroimidazooxazine, PA-824, is caused by mutations in an F420 -dependent bio-activation pathway. We investigated whether the same mechanisms are responsible for resistance to delamanid. Spontaneous resistance frequencies were determined using M. bovis BCG Tokyo (BCG) and M. tuberculosis H37Rv. F420 high-performance liquid chromatography (HPLC) elution patterns of homogenates of delamanid-resistant BCG colonies and two previously identified delamanid-resistant M...
January 2018: Tuberculosis
Karen Rego, Kristen Pereira, James MacDougall, William Cruikshank
BACKGROUND: Accurate identification of individuals with TB infection, is required to achieve the WHO's End TB Strategy goals. While there is general acceptance that the T-SPOT.TB test borderline category provides an opportunity to increase test resolution of results around the test cut-off point, this has not been investigated. METHODS: 645,947 tests were analyzed to determine frequency of borderline results, effect of age and time between tests and associations between subjects' clinical risk factors and retest results...
January 2018: Tuberculosis
Nastassja L Kriel, James Gallant, Niël van Wyk, Paul van Helden, Samantha L Sampson, Robin M Warren, Monique J Williams
Nucleoid associated proteins (NAPs) are known organisers of chromosomal structure and regulators of transcriptional expression. The number of proposed NAPs in mycobacteria are significantly lower than the number identified in other organisms. An interesting feature of mycobacterial NAPs is their low sequence similarity with those in other species, a property that has hindered their identification. In this review, we discuss the current evidence for the proposed classification of six mycobacterial proteins, Lsr2, EspR, mIHF, HupB, MDP2 and NapM, as NAPs in mycobacterial species with an emphasis on their roles in modulating chromosome structure and transcriptional regulation...
January 2018: Tuberculosis
Oksana Pasechnik, Anna Vyazovaya, Stanislav Vitriv, Marina Tatarintseva, Aleksey Blokh, Vladimir Stasenko, Igor Mokrousov
This population-based study characterized Mycobacterium tuberculosis isolates from HIV-positive and HIV-negative tuberculosis (TB) patients in the Omsk region in Western Siberia, Russia. We sought to gain insight into the major genotype families and epidemic and endemic clones of M. tuberculosis in the area with a high burden and adverse trend of TB/HIV coinfection. The study collection included M. tuberculosis isolates from 207 newly-diagnosed patients with pulmonary TB; 55 (26.5%) of patients were HIV-infected...
January 2018: Tuberculosis
Amandeep Singh, M Vijayan, Umesh Varshney
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...
January 2018: Tuberculosis
Matthew W Marney, Robert P Metzger, David Hecht, Faramarz Valafar
WHO reported 10.4 million new tuberculosis (TB) cases and 1.8 million deaths in 2015, making M. tuberculosis the most successful human pathogen with highest mortality among infectious diseases [1,2]. Drug-resistant TB is a major threat to global TB control [2,3]. Recently Torres et al. [4] identified 14 novel substitutions in M. tuberculosis-KatG (the enzyme associated with resistance to isoniazid-an important first-line anti-TB drug) and demonstrated that 12 of the 14 can cause INH-resistance in M. smegmatis...
January 2018: Tuberculosis
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