scholarly journals Impact of Genomics on Clarifying the Evolutionary Relationships amongst Mycobacteria: Identification of Molecular Signatures Specific for the Tuberculosis-Complex of Bacteria with Potential Applications for Novel Diagnostics and Therapeutics

2018 ◽  
Vol 7 (4) ◽  
pp. 31 ◽  
Author(s):  
Radhey S. Gupta
Keyword(s):  
Comparative Genomic ◽  
Drug Resistant ◽  
Cellular Functions ◽  
Tuberculosis Complex ◽  
Genomic Analyses ◽  
Potential Applications ◽  
Resistant Strains ◽  
Novel Interactions ◽  
Drug Resistant Strains ◽  
High Degree

An alarming increase in tuberculosis (TB) caused by drug-resistant strains of Mycobacterium tuberculosis has created an urgent need for new antituberculosis drugs acting via novel mechanisms. Phylogenomic and comparative genomic analyses reviewed here reveal that the TB causing bacteria comprise a small group of organisms differing from all other mycobacteria in numerous regards. Comprehensive analyses of protein sequences from mycobacterial genomes have identified 63 conserved signature inserts and deletions (indels) (CSIs) in important proteins that are distinctive characteristics of the TB-complex of bacteria. The identified CSIs provide potential means for development of novel diagnostics as well as therapeutics for the TB-complex of bacteria based on four key observations: (i) The CSIs exhibit a high degree of exclusivity towards the TB-complex of bacteria; (ii) Earlier work on CSIs provide evidence that they play important/essential functions in the organisms for which they exhibit specificity; (iii) CSIs are located in surface-exposed loops of the proteins implicated in mediating novel interactions; (iv) Homologs of the CSIs containing proteins, or the CSIs in such homologs, are generally not found in humans. Based on these characteristics, it is hypothesized that the high-throughput virtual screening for compounds binding specifically to the CSIs (or CSI containing regions) and thereby inhibiting the cellular functions of the CSIs could lead to the discovery of a novel class of drugs specifically targeting the TB-complex of organisms.

Recent Developments and Novel Drug Delivery Strategies for the Treatment of Tuberculosis

2019 ◽  
Vol 12 (3) ◽  
pp. 4524-4530
Author(s):  
Yonas Brhane ◽  
Tesfaye Gabriel ◽  
Tigist Adane ◽  
Yemisrach Negash ◽  
Henok Mulugeta ◽  
...  
Keyword(s):  
Drug Delivery ◽  
Mycobacterium Tuberculosis Complex ◽  
Drug Resistant ◽  
Tuberculosis Complex ◽  
Innovative Drug ◽  
Recent Developments ◽  
Resistant Strains ◽  
Delivery Strategies ◽  
Drug Resistant Strains ◽  
Novel Drug

Tuberculosis (TB) is a contagious infectious illness caused by species having a place with the Mycobacterium tuberculosis complex. The clinical management of tuberculosis still remains a difficult task. Treatment of TB with anti-tubercular drugs becomes the only option available. Hence, the goals of treatment are ensure cure without relapse, prevent death, impede transmission, and prevent emergence of drug resistant strains. This review describes the latest developments and innovative drug delivery strategies for treatment of TB in order to improve the therapeutic efficacy and reduce toxic effect of anti-tubercular agents and enhance patient compliance with concomitant decrease in drug interaction. Among different novel drug delivery systems Niosomes, Liposomes, Dendrimers, Cyclodextrins, Microencapsulation, Alginates and Hydrogels have been described as new drug delivery strategies of anti-tubercular agents. 

scholarly journals Comparative Genomic Analysis of Mycobacterium tuberculosis Drug Resistant Strains from Russia

PLoS ONE ◽  
2013 ◽  
Vol 8 (2) ◽  
pp. e56577 ◽  
Author(s):  
Elena N. Ilina ◽  
Egor A. Shitikov ◽  
Larisa N. Ikryannikova ◽  
Dmitry G. Alekseev ◽  
Dmitri E. Kamashev ◽  
...  
Keyword(s):  
Mycobacterium Tuberculosis ◽  
Genomic Analysis ◽  
Comparative Genomic Analysis ◽  
Comparative Genomic ◽  
Drug Resistant ◽  
Resistant Strains ◽  
Drug Resistant Strains

scholarly journals The Mycobacterium tuberculosis CRISPR-Associated Cas1 Involves Persistence and Tolerance to Anti-Tubercular Drugs

2019 ◽  
Vol 2019 ◽  
pp. 1-9 ◽  
Author(s):  
Jiawei Wei ◽  
Nan Lu ◽  
Zhiying Li ◽  
Xuanyan Wu ◽  
Tao Jiang ◽  
...  
Keyword(s):  
Mycobacterium Tuberculosis ◽  
Mycobacterium Smegmatis ◽  
Drug Resistant ◽  
Tuberculosis Complex ◽  
Antitubercular Drugs ◽  
Resistance Evolution ◽  
Associated Proteins ◽  
Resistant Strains ◽  
Drug Resistant Strains ◽  
Rapid Emergence

Tuberculosis remains one of the leading causes of death worldwide. Even if new antitubercular drugs are currently being developed, the rapid emergence and spread of drug-resistant strain remain a severe challenge. The CRISPR associated proteins 1 (Cas1), a most conserved endonuclease which is responsible for spacer integration into CRISPR arrays, was found deleted in many specific drug-resistant strains. The function of Cas1 is still unknown in Mycobacterium type III-A CRISPR family. In this study, the Cas1 (Rv2817c) defect was found in 57.14% of clinical isolates. To investigate the function of Cas1 in new spacer acquisition, we challenged Bacillus Calmette–Guérin (BCG) with a mycobacteriophage D29. Newly acquired spacer sequence matches D29 genome was not found by spacer deep-sequencing. We further expressed Cas1 in recombinant Mycobacterium smegmatis. We found that Cas1 increased the sensitivity to multiple anti-tuberculosis drugs by reducing the persistence during drug treatment. We also showed that Cas1 impaired the repair of DNA damage and changed the stress response of Mycobacterium smegmatis. This study provides a further understanding of Cas1 in Mycobacterium tuberculosis complex (MTBC) drug-resistance evolution and a new sight for the tuberculosis treatment.

scholarly journals Attaching Zanamivir to a Polymer Markedly Enhances Its Activity Against Drug-resistant Strains of Influenza a Virus

2011 ◽  
Vol 100 (3) ◽  
pp. 831-835 ◽  
Author(s):  
Alisha K. Weight ◽  
Jayanta Haldar ◽  
Luis Álvarez de Cienfuegos ◽  
Larisa V. Gubareva ◽  
Terrence M. Tumpey ◽  
...  
Keyword(s):  
Influenza A Virus ◽  
Influenza A ◽  
Drug Resistant ◽  
Resistant Strains ◽  
Drug Resistant Strains

DRUG RESISTANT STRAINS OF PLASMODIUM FALCIPARUM IN PAPUA NEW GUINEA

The Lancet ◽  
1981 ◽  
Vol 317 (8216) ◽  
pp. 386
Author(s):  
Brian Darlow ◽  
Helena Vrbova ◽  
John Stace ◽  
Peter Heywood ◽  
Michael Alpers
Keyword(s):  
Plasmodium Falciparum ◽  
Papua New Guinea ◽  
New Guinea ◽  
Drug Resistant ◽  
Resistant Strains ◽  
Drug Resistant Strains

Tigecycline for Treatment of Nosocomial-Acquired Pneumonia Possibly Caused by Multi-Drug Resistant Strains ofStenotrophomonas maltophilia

2008 ◽  
Vol 20 (6) ◽  
pp. 761-763 ◽  
Author(s):  
D. Blanquer ◽  
J. De Otero ◽  
E. Padilla ◽  
F. Gòmez ◽  
A. Mayol ◽  
...  
Keyword(s):  
Drug Resistant ◽  
Resistant Strains ◽  
Drug Resistant Strains

scholarly journals The Effects of Oral Liposomal Glutathione and In Vitro Everolimus in Altering the Immune Responses against Mycobacterium bovis BCG Strain in Individuals with Type 2 Diabetes

2021 ◽  
Vol 12 (1) ◽  
pp. 16-26
Author(s):  
Kimberly To ◽  
Ruoqiong Cao ◽  
Aram Yegiazaryan ◽  
James Owens ◽  
Kayvan Sasaninia ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Immune Cells ◽  
Mycobacterial Infection ◽  
Drug Resistant ◽  
Tnf Α ◽  
Resistant Strains ◽  
Ifn Γ ◽  
Drug Resistant Strains

Abstract Tuberculosis (TB) caused by Mycobacterium tuberculosis (M. tb) still remains a devastating infectious disease in the world. There has been a daunting increase in the incidence of Type 2 Diabetes Mellitus (T2DM) worldwide. T2DM patients are three times more vulnerable to M. tb infection compared to healthy individuals. TB-T2DM coincidence is a challenge for global health control. Despite some progress in the research, M. tb still has unexplored characteristics in successfully evading host defenses. The lengthy duration of treatment, the emergence of multi-drug-resistant strains and extensive-drug-resistant strains of M. tb have made TB treatment very challenging. Previously, we have tested the antimycobacterial effects of everolimus within in vitro granulomas generated from immune cells derived from peripheral blood of healthy subjects. However, the effectiveness of everolimus treatment against mycobacterial infection in individuals with T2DM is unknown. Furthermore, the effectiveness of the combination of in vivo glutathione (GSH) supplementation in individuals with T2DM along with in vitro treatment of isolated immune cells with everolimus against mycobacterial infection has never been tested. Therefore, we postulated that liposomal glutathione (L-GSH) and everolimus would offer great hope for developing adjunctive therapy for mycobacterial infection. L-GSH or placebo was administered to T2DM individuals orally for three months. Study subjects’ blood was drawn pre- and post-L-GSH/or placebo supplementation, where Peripheral Blood Mononuclear Cells (PBMCs) were isolated from whole blood to conduct in vitro studies with everolimus. We found that in vitro treatment with everolimus, an mTOR (membrane target of rapamycin) inhibitor, significantly reduced intracellular M. bovis BCG infection alone and in conjunction with L-GSH supplementation. Furthermore, we found L-GSH supplementation coupled with in vitro everolimus treatment produced a greater effect in inhibiting the growth of intracellular Mycobacterium bovis BCG, than with the everolimus treatment alone. We also demonstrated the functions of L-GSH along with in vitro everolimus treatment in modulating the levels of cytokines such as IFN-γ, TNF-α, and IL-2 and IL-6, in favor of improving control of the mycobacterial infection. In summary, in vitro everolimus-treatment alone and in combination with oral L-GSH supplementation for three months in individuals with T2DM, was able to increase the levels of T-helper type 1 (Th1) cytokines IFN-γ, TNF-α, and IL-2 as well as enhance the abilities of granulomas from individuals with T2DM to improve control of a mycobacterial infection.

7,8-dihydroxyflavone-functionalized gold nanoparticles target the arginase enzyme of Leishmania donovani

Nanomedicine ◽  
2021 ◽  
Author(s):  
Pragya Prasanna ◽  
Prakash Kumar ◽  
Saptarshi Mandal ◽  
Tanvi Payal ◽  
Saurabh Kumar ◽  
...  
Keyword(s):  
Gold Nanoparticles ◽  
Leishmania Donovani ◽  
Drug Resistant ◽  
X Ray Diffraction ◽  
High Biological Activity ◽  
Transmission Electron ◽  
Resistant Strains ◽  
Low Cytotoxicity ◽  
Drug Resistant Strains ◽  
Parasite Leishmania

Aim: To analyze the efficacy and possible mechanism of action of 7,8-dihydroxyflavone (DHF) and DHF synthesized gold nanoparticles (GNPs) against the parasite Leishmania donovani. Methods: GNPs were synthesized using DHF and characterized by dynamic light scattering, ζ potential, Fourier transform infrared spectroscopy, transmission electron microscopy and x-ray diffraction. The efficacy of DHF and DHF-GNP were tested against sensitive and drug-resistant parasites. GNP uptake was measured on macrophages by atomic absorption spectroscopy. Results: DHF and DHF-GNP (∼35 nm) were equally effective against sensitive and drug-resistant strains and inhibited the arginase activity of parasites. Increased IFN-γ and reduced IL-12 cytokine response showed a Th1/Th2-mediated cell death in macrophages. Conclusion: The low cytotoxicity and high biological activity of DHF-GNP may be useful for chemotherapy of leishmaniasis.

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