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Mtb protein

Dhanashree Lokesh, Raman Parkesh, Rajagopal Kammara
Multiple mutations in the β subunit of the RNA polymerase (rpoβ) of Mycobacterium tuberculosis (Mtb) are the primary cause of resistance to rifamycin (RIF). In the present study, bifidobacterial rpoβ sequences were analyzed to characterize the mutations that contribute to the development of intrinsic resistance to RIF, isoniazid, streptomycin and pyrazinamide. Sequence variations, which mapped to cassettes 1 and 2 of the rpoβ pocket, are also found in multidrug-resistant Mtb (MDR Mtb). Growth curves in the presence of osmolytes and different concentrations of RIF showed that the bacteria adapted rapidly by shortening the growth curve lag time...
August 9, 2018: Scientific Reports
Elisa Nemes, Thomas J Scriba, Mark Hatherill
PURPOSE OF REVIEW: To outline the need for a new tuberculosis (TB) vaccine; challenges for induction of vaccine-mediated protection in HIV-infected persons; and recent advances in clinical development. RECENT FINDINGS: HIV has a detrimental effect on T-cell function, polarization and differentiation of Mycobacterium tuberculosis (Mtb)-specific T cells, Mtb antigen presentation by dendritic cells, and leads to B-cell and antibody-response deficiencies. Previous observations of protection against TB disease in HIV-infected persons by Mycobacterium obuense suggest that an effective vaccine against HIV-related TB is feasible...
August 4, 2018: Current Opinion in HIV and AIDS
Tungadri Bose, Chandrani Das, Anirban Dutta, Vishnuvardhan Mahamkali, Sudipta Sadhu, Sharmila S Mande
BACKGROUND: Mycobacterium tuberculosis infection in humans is often associated with extended period of latency. To adapt to the hostile hypoxic environment inside a macrophage, M. tuberculosis cells undergo several physiological and metabolic changes. Previous studies have mostly focused on inspecting individual facets of this complex process. In order to gain deeper insights into the infection process and to understand the coordination among different regulatory/ metabolic pathways in the pathogen, the current in silico study investigates three aspects, namely, (i) host-pathogen interactions (HPIs) between human and M...
July 27, 2018: BMC Genomics
Kent Koster, Angela Largen, Jeffrey T Foster, Kevin P Drees, Lishi Qian, Edward P Desmond, Xuehua Wan, Shaobin Hou, James T Douglas
While tuberculosis (TB) remains a global disease, the WHO estimates that 62% of the incident TB cases in 2016 occurred in the WHO South-East Asia and Western Pacific regions. TB in the Pacific is composed predominantly of two genetic families of Mycobacterium tuberculosis (Mtb): Beijing and Manila. The Manila family is historically under-studied relative to the families that comprise the majority of TB in Europe and North America (e.g. lineage 4), and it remains unclear why this lineage has persisted in Filipino populations despite the predominance of more globally successful Mtb lineages in most of the world...
2018: PloS One
Padam Singh, Shashi Kant Kumar, Vineet Kumar Maurya, Basant Kumar Mehta, Hafsa Ahmad, Anil Kumar Dwivedi, Vinita Chaturvedi, Tejender S Thakur, Sudhir Sinha
A synthetic molecule S006-830, belonging to the class of thiophene-containing trisubstituted methanes, had shown good in vitro and in vivo bactericidal activity against drug-sensitive and drug-resistant Mycobacterium tuberculosis (Mtb). The molecule had also shown good druglike pharmacokinetic properties. However, S006-830 is a racemic mixture of two enantiomers, one of which could possess a better pharmacological profile than the other. We purified both the enantiomers on a chiral column and observed that S-enantiomer has a significantly higher inhibitory and cidal activity against Mtb than the R-enantiomer...
November 30, 2017: ACS Omega
Jun Lou, Yongli Wang, Ximing Zheng, Weiqiang Qiu
Autophagy is a crucial host-defense mechanism against Mycobacterium tuberculosis (Mtb) infection by spanning innate and adaptive immune functions. TRIM22 is a member of tripartite motif family protein which involved in innate immunity and autophagy process. However, its role in the modulation of bacterial infection has not been investigated. Here, we demonstrated that TRIM22 is upregulated in a dose-dependent and time-dependent manner during Mtb infection of THP-1 cells. Downregulation of TRIM22 significantly decreased light chain 3 (LC3)-II protein level and the formation of LC3 puncta, while it markedly increased SQSTM1, a marker of autophagic degradation, in Mtb-infected THP-1 cells...
July 16, 2018: Journal of Cellular Biochemistry
Sylvia Annabel Dass, Mohd Nor Norazmi, Armando Acosta Dominguez, Maria Elena Sarmiento Garcia San Miguel, Gee Jun Tye
The discovery of heat shock protein 16 kDa antigen protein has deepen the understanding of latent tuberculosis since it was found to be primarily expressed by Mycobacterium tuberculosis during latent phase leading to the rapid optimization and development in terms of diagnosis and therapeutics. Recently, T cell receptor-like antibody has been explored extensively targeting various diseases due to its dual functionality (T cell receptor and antibody). In this study, a TCR-like domain antibody (A2/Ab) with the binding capacity to Mtb heat shock protein (HSP) 16 kDa antigen presented by major histocompatible complex (MHC) HLA-A*02 was successfully generated via biopanning against human domain antibody library...
July 4, 2018: Molecular Immunology
K Pratima, N Goud, Arifuddin Mohammed, Gayathri Ramamoorthy, Ragamanvitha Ananthathatmula, Mukesh Doble, Arshad Rizvi, Sharmista Banerjee, Ravi Alvala, Mallika Alvala
The rising multidrug-resistant Mycobacterium tuberculosis (Mtb) strain made current anti-TB drug therapy ineffective and became a major health concern globally; hence it is crucial to develop new molecules against vital targets with a novel mechanism. Mtb Filamenting temperature sensitive protein Z (FtsZ), a tubulin homolog plays a major role in bacterial cell division, in the presence of GTP recruiting essential proteins for cell division and considered to be a potential target for drug discovery. Most of MtbFtsZ inhibitors known are of antibiotics from natural resources and suffer from cellular uptake, specificity...
July 13, 2018: Chemical Biology & Drug Design
Kamakshi Prudhula Devalraju, Venkata Sanjeev Kumar Neela, Sharadambal Sunder Ramaseri, Arunabala Chaudhury, Abhinav Van, Siva Sai Krovvidi, Ramakrishna Vankayalapati, Vijaya Lakshmi Valluri
BACKGROUND: IL-17 and IL-22 cytokines play an important role in protective immune responses against Mycobacterium tuberculosis (Mtb) infection. Information on the production of these cytokines and the factors that regulate their production in the context of human immunodeficiency virus (HIV) and latent tuberculosis infection (LTBI) or active tuberculosis disease (ATB) is limited. In the current study, we compared the production of these two cytokines by PBMC of HIV-LTBI+ and HIV + LTBI+ individuals in response to Mtb antigens CFP-10 (culture filtrate protein) and ESAT-6 (Early Secretory Antigenic Target)...
July 11, 2018: BMC Infectious Diseases
Ameeruddin Nusrath Unissa, George Priya Doss C, Thirumal Kumar, Swathi Sukumar, Appisetty Ramya Lakshmi, Luke Elizabeth Hanna
OBJECTIVES: Isoniazid (INH) is still the most important first-line anti-tuberculosis (TB) drug. Resistance to this drug is regarded as a major impediment on the TB control program and to the emergence of multidrug-resistant strains. Mutations at position 315 in the katG gene which codes for catalase-peroxidase (KatG) enzyme, is the major cause for INH resistance in Mycobacterium tuberculosis (MTB). Therefore, investigation into the molecular mechanisms of INH resistance is the need of the hour...
July 7, 2018: Journal of Global Antimicrobial Resistance
Kalicharan Sharma, Omprakash Tanwar, Shweta Sharma, Shakir Ali, M M Alam, M S Zaman, Mymoona Akhter
Tuberculosis is an infectious disease that affects millions of population every year. Mtb-DHFR is a validated target that is vital for nucleic acids biosynthesis and therefore DNA formation and cell replication. This paper report identification and synthesis of novel compounds for selective inhibition of Mtb-DHFR and unleash the selective structural features necessary to inhibit the same. Virtual screening of databases was carried out to identify novel compounds on the basis of difference between the binding pockets of the two proteins...
May 11, 2018: Bioorganic Chemistry
Ryan M Kramer, Michelle C Archer, Mark T Orr, Natasha Dubois Cauwelaert, Elyse A Beebe, Po-Wei D Huang, Quinton M Dowling, Alicia M Schwartz, Dawn M Fedor, Thomas S Vedvick, Christopher B Fox
Background: Adjuvants have the potential to increase the efficacy of protein-based vaccines but need to be maintained within specific temperature and storage conditions. Lyophilization can be used to increase the thermostability of protein pharmaceuticals; however, no marketed vaccine that contains an adjuvant is currently lyophilized, and lyophilization of oil-in-water nanoemulsion adjuvants presents a specific challenge. We have previously demonstrated the feasibility of lyophilizing a candidate adjuvanted protein vaccine against Mycobacterium tuberculosis ( Mtb ), ID93 + GLA-SE, and the subsequent improvement of thermostability; however, further development is required to prevent physicochemical changes and degradation of the TLR4 agonist glucopyranosyl lipid adjuvant formulated in an oil-in-water nanoemulsion (SE)...
2018: International Journal of Nanomedicine
Gundeep Kaur, Soni Kaundal, Srajan Kapoor, Jonathan M Grimes, Juha T Huiskonen, Krishan Gopal Thakur
CarD is an essential global transcription regulator from Mycobacterium tuberculosis (Mtb) that binds RNA polymerase and activates transcription by stabilizing the transcription initiation complex. Available crystal structures have captured two distinct, monomeric and domain-swapped homodimeric, oligomeric states of CarD. However, the actual oligomeric state of CarD in solution and its biological relevance has remained unclear. Here, we confirm the presence of the homodimeric state of CarD in solution by using synchrotron-based small-angle X-ray scattering...
July 4, 2018: Scientific Reports
Yichuan Gan, Cong Wang, Yimin Fang, Yanan Yao, Xiaoxin Tu, Jiao Wang, Xi Huang, Yaoju Tan, Tao Chen, Kouxing Zhang, Yanming Shen, Lin Zhou, Jianxiong Liu, Xiaomin Lai
Human CD4+ T cells play an important role in the immune response to Mycobacterium tuberculosis (MTB). However, little is known about the spectratyping characteristics of the CD4+ T-cell receptor (TCR) α- and β-chains CDR3 region in tuberculosis (TB) patients. We sorted MTB peptide E7-bound CD4+ T cells by using E7/HLA-DR tetramers constructed with different HLA-DRB1 alleles and extracted the CDR3 amino-acid sequences of TCR α- and β-chains. The results showed that the CDR3 sequences of E7-bound CD4+ T cells were completely or partially identical in a single patient...
July 2, 2018: Scientific Reports
Wenjing Wang, Baozhi Yang, Yong Cui, Ying Zhan
Spinal tuberculosis (ST) is the tuberculosis caused by Mycobacterium tuberculosis ( Mtb ) infections in spinal curds. Isoliquiritigenin 4,2',4'-trihydroxychalcone, ISL) is an anti-inflammatory flavonoid derived from licorice ( Glycyrrhiza uralensis ), a Chinese traditional medicine. In this study, we evaluated the potential of ISL in treating ST in New Zealand white rabbit models. In the model, rabbits (n=40) were infected with Mtb strain H37Rv or not in their 6th lumbar vertebral bodies. Since the day of infection, rabbits were treated with 20 mg/kg and 100 mg/kg of ISL respectively...
July 2018: Korean Journal of Physiology & Pharmacology
Suyu Mei, Erik K Flemington, Kun Zhang
BACKGROUND: Bacterial invasive infection and host immune response is fundamental to the understanding of pathogen pathogenesis and the discovery of effective therapeutic drugs. However, there are very few experimental studies on the signaling cross-talks between bacteria and human host to date. METHODS: In this work, taking M. tuberculosis H37Rv (MTB) that is co-evolving with its human host as an example, we propose a general computational framework that exploits the known bacterial pathogen protein interaction networks in STRING database to predict pathogen-host protein interactions and their signaling cross-talks...
June 28, 2018: BMC Genomics
Geanncarlo Lugo-Villarino, Anthony Troegeler, Luciana Balboa, Claire Lastrucci, Carine Duval, Ingrid Mercier, Alan Bénard, Florence Capilla, Talal Al Saati, Renaud Poincloux, Ivanela Kondova, Frank A W Verreck, Céline Cougoule, Isabelle Maridonneau-Parini, Maria Del Carmen Sasiain, Olivier Neyrolles
DC-SIGN (CD209/CLEC4L) is a C-type lectin receptor (CLR) that serves as a reliable cell-surface marker of interleukin 4 (IL-4)-activated human macrophages [M(IL-4)], which historically represent the most studied subset within the M2 spectrum of macrophage activation. Although DC-SIGN plays important roles in Mycobacterium tuberculosis (Mtb) interactions with dendritic cells, its contribution to the Mtb-macrophage interaction remains poorly understood. Since high levels of IL-4 are correlated with tuberculosis (TB) susceptibility and progression, we investigated the role of DC-SIGN in M(IL-4) macrophages in the TB context...
2018: Frontiers in Immunology
Yogesh Patil, Ramesh Shingare, Amit Choudhari, Rachana Borkute, Dhiman Sarkar, Balaji R Madje
A series of new tricyclic pyrrolo[3,2-e]tetrazolo[1,5-c]pyrimidines 8a-l were synthesized and characterized by IR, NMR (1 H and 13 C), and mass spectral analysis. The newly synthesized compounds 8a-l were inspected for their in vitro antitubercular activity against Mycobacterium tuberculosis (MTB) H37 Ra using an established XTT reduction menadione assay (XRMA). The title compounds exhibited minimum inhibitory concentrations (MIC90 ) ranging from 0.09 to >30 μg/mL. Five compounds (8c, 8i-l) were further confirmed for their dose-dependent effect against MTB...
June 25, 2018: Archiv der Pharmazie
Zhengzhong Xu, Aihong Xia, Xin Li, Zhaocheng Zhu, Yechi Shen, Shanshan Jin, Tian Lan, Yuqing Xie, Han Wu, Chuang Meng, Lin Sun, Yuelan Yin, Xiang Chen, Xinan Jiao
BACKGROUND: Control of Mycobacterium tuberculosis (Mtb) infection requires CD4+ T-cell responses and major histocompatibility complex class II (MHC II) presentation of Mtb antigens (Ags). Dendritic cells (DCs) are the most potent of the Ag-presenting cells and are central to the initiation of T-cell immune responses. Much research has indicated that DCs play an important role in anti-mycobacterial immune responses at early infection time points, but the kinetics of Ag presentation by these cells during these events are incompletely understood...
June 25, 2018: BMC Immunology
Behrouz Golichenari, Rahim Nosrati, Aref Farokhi-Fard, Khalil Abnous, Farzam Vaziri, Javad Behravan
Tuberculosis is a major global health problem caused by the bacterium Mycobacterium tuberculosis (Mtb) complex. According to WHO reports, 53 million TB patients died from 2000 to 2016. Therefore, early diagnosis of the disease is of great importance for global health care programs. The restrictions of traditional methods have encouraged the development of innovative methods for rapid, reliable, and cost-effective diagnosis of tuberculosis. In recent years, aptamer-based biosensors or aptasensors have drawn great attention to sensitive and accessible detection of tuberculosis...
June 11, 2018: Biosensors & Bioelectronics
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