scholarly journals Comparative Analysis of non-coding small-RNAs in P. aeruginosa Keratitis Strains with Different Antibiotic Susceptibility

2021 ◽  
Author(s):  
Kathirvel Kandasamy ◽  
Bharanidharan Devarajan
Keyword(s):  
Drug Resistance ◽  
Bioinformatic Analysis ◽  
Negative Regulation ◽  
Multi Drug Resistance ◽  
Steady Increase ◽  
Functional Studies ◽  
Physiological Processes ◽  
Porin Protein ◽  
Geographical Regions ◽  
Imipenem Resistance

Pseudomonas aeruginosa, is a gram-negative bacterium causes opportunistic or nosocomial infections in immunocompromised individuals. In recent years, a steady increase in human corneal infections of P. aeruginosa has been reported with increased multi-drug resistance (MDR) or extensively drug resistance (XDR). Several non-coding sRNAs, has been identified to regulate various physiological processes in P. aeruginosa, including biofilm formation, quorum sensing. However, the regulatory mechanism of sRNAs in MDR/XDR pathways of P. aeruginosa keratitis strains is not yet studied. In this study, we identified bacterial sRNAs in publicly available P. aeruginosa keratitis genomes and investigated their regulatory role in MDR/XDR pathways using bioinformatic analysis. Totally, 46 P. aeruginosa keratitis strains from different geographical regions were included. Of 46, Eight (30%) out of Twenty-seven and Nine (52%) out of Nineteen P. aeruginosa strains from India and Australia were identified as not-MDR. Whereas, 10 (38%) Indian and 9 (47%) Australian strains were identified as MDR. Eight Indian strains were identified as XDR. Out of 46 strains, 23 (50%) carried ExoU, 21(45%) carried ExoS and two (5%) strains carried both ExoU and ExoS, exotoxins for their virulence. The sRNA, SPA0021 was identified in 18 MDR/XDR and 6 not-MDR strains along with UCBPP-PA14. Interestingly, majority of the imipenem resistant P. aeruginosa keratitis strains from the present study was found to be carried SPA0023 sRNA (18 out of 30 strains). The outer membrane porin protein OprD, identified as binding target of SPA0023. Negative regulation or inactivation of OprD, reported in increased imipenem resistance in P. aeruginosa. Mutation analysis revealed that SPA0023 carrying P. aeruginosa keratitis strains contains a lesser number of amino acid changes in OprD protein than other strains. These findings indicate, imipenem resistance in SPA0023 carried strains might arose from the negative regulation or inhibition of OprD by SPA0023. However, functional studies are warranted with large number of P. aeruginosa keratitis strains to confirm the negative regulation of OprD by SPA0023 and imipenem resistance.

scholarly journals Canine multi-drug resistance-1 mutation prevalence: A South African perspective

2014 ◽  
Vol 85 (1) ◽  
Author(s):  
Lérica Le Roux-Pullen ◽  
Henriëtte Van der Zwan
Keyword(s):  
Drug Resistance ◽  
South African ◽  
Gene Mutation ◽  
Macrocyclic Lactone ◽  
Multi Drug Resistance ◽  
Prevalence Data ◽  
Geographical Regions ◽  
African Perspective ◽  
Mdr 1

The multi-drug resistance (mdr-1) gene mutation is a phenomenon well known to current veterinary practitioners. The mutation causes a predisposition for, amongst other phenomena, macrocyclic lactone-induced neurotoxicosis in affected canines, a condition that can be fatal. Various herding dog breeds can be heterozygous or homozygous for the mutation, and prevalence differs only slightly in dog populations between geographical regions. This report provides prevalence data of the canine mdr-1 mutation in 306 South African dogs.

scholarly journals The Role Played by Wnt/β-Catenin Signaling Pathway in Acute Lymphoblastic Leukemia

2020 ◽  
Vol 21 (3) ◽  
pp. 1098 ◽  
Author(s):  
Francesca Chiarini ◽  
Francesca Paganelli ◽  
Alberto M. Martelli ◽  
Camilla Evangelisti
Keyword(s):  
Drug Resistance ◽  
Acute Lymphoblastic Leukemia ◽  
Therapeutic Potential ◽  
Lymphoblastic Leukemia ◽  
Current Status ◽  
Multi Drug Resistance ◽  
Hematopoietic Malignancies ◽  
Physiological Processes ◽  
Signaling Axis ◽  
B Cell Precursors

Acute lymphoblastic leukemia (ALL) is an aggressive hematologic neoplastic disorder that arises from the clonal expansion of transformed T-cell or B-cell precursors. Thanks to progress in chemotherapy protocols, ALL outcome has significantly improved. However, drug-resistance remains an unresolved issue in the treatment of ALL and toxic effects limit dose escalation of current chemotherapeutics. Therefore, the identification of novel targeted therapies to support conventional chemotherapy is required. The Wnt/β-catenin pathway is a conserved signaling axis involved in several physiological processes such as development, differentiation, and adult tissue homeostasis. As a result, deregulation of this cascade is closely related to initiation and progression of various types of cancers, including hematological malignancies. In particular, deregulation of this signaling network is involved in the transformation of healthy HSCs in leukemic stem cells (LSCs), as well as cancer cell multi-drug-resistance. This review highlights the recent findings on the role of Wnt/β-catenin in hematopoietic malignancies and provides information on the current status of Wnt/β-catenin inhibitors with respect to their therapeutic potential in the treatment of ALL.

Strategies to Overcome Multi-Drug Resistance in Cancer Cells: the Contribution of siRNA and Nanotechnologies

2016 ◽  
Vol 20 (28) ◽  
pp. 2971-2982
Author(s):  
Cristina Mambet ◽  
Mihaela Chivu-Economescu ◽  
Lilia Matei ◽  
Mihai Stoian ◽  
Coralia Bleotu
Keyword(s):  
Drug Resistance ◽  
Cancer Cells ◽  
Multi Drug Resistance

Current insights into the chemistry and antitubercular potential of benzimidazole and imidazole derivatives

2020 ◽  
Vol 20 ◽  
Author(s):  
Deepa Parwani ◽  
Sushanta Bhattacharya ◽  
Akash Rathore ◽  
Chaitali Mallick ◽  
Vivek Asati ◽  
...  
Keyword(s):  
Drug Resistance ◽  
Mycobacterium Tuberculosis ◽  
Multi Drug Resistance ◽  
Benzimidazole Derivatives ◽  
Duration Of Treatment ◽  
Structure Activity ◽  
Mdr Tb ◽  
Low Toxicity ◽  
Extensively Drug Resistance ◽  
Improved Characteristics

: Tuberculosis is a disease caused by Mycobacterium tuberculosis (Mtb), affecting millions of people worldwide. The emergence of drug resistance is a major problem in the successful treatment of tuberculosis. Due to the commencement of MDR-TB (multi-drug resistance) and XDR-TB (extensively drug resistance), there is a crucial need for the development of novel anti-tubercular agents with improved characteristics such as low toxicity, enhanced inhibitory activity and short duration of treatment. In this direction, various heterocyclic compounds have been synthesized and screened against Mycobacterium tuberculosis. Among them, benzimidazole and imidazole containing derivatives found to have potential anti-tubercular activity. The present review focuses on various imidazole and benzimidazole derivatives (from 2015-2019) with their structure activity relationships in the treatment of tuberculosis.

4-Aryl-1,4-Dihydropyridines as Potential Enoyl-Acyl Carrier Protein Reductase Inhibitors: Antitubercular Activity and Molecular Docking Study

2020 ◽  
Vol 20 ◽  
Author(s):  
Katharigatta N. Venugopala ◽  
Christophe Tratrat ◽  
Melendhran Pillay ◽  
Pran Kishore Deb ◽  
Deepak Chopra ◽  
...  
Keyword(s):  
Drug Resistance ◽  
Acyl Carrier Protein ◽  
Phenyl Group ◽  
Antitubercular Activity ◽  
Docking Study ◽  
Benzyl Ester ◽  
Multi Drug Resistance ◽  
Carrier Protein ◽  
Molecular Docking Study ◽  
Lipinski’S Rule

Background: Tuberculosis remains one of the most deadly infectious diseases worldwide due to the emergence of multi-drug resistance (MDR) and extensively drug resistance (XDR) strains of Mycobacterium tuberculosis (MTB). Materials and Methods: Herein, the screening of a total of eight symmetrical 1,4-dihydropyridine (1,4-DHP) derivatives (4a-4h) was carried out for whole-cell anti-TB activity against the susceptible H37Rv and MDR strains of MTB. Results and Discussion: Most of the compounds exhibited moderate to excellent activity against the susceptible H37Rv. Moreover, the most promising compound 4f (against H37Rv) having para-trifluoromethyl phenyl group at 4-position and bis para-methoxy benzyl ester group at 3- and 5-positions of 1,4-dihydropyridine pharmacophore, exhibited no toxicity, but demonstrated weak activity against MTB strains resistant to isoniazid and rifampicin. In light of the inhibitory profile of the title compounds, enoyl-acyl carrier protein reductase (InhA) appeared to be the appropriate molecular target. Docking study of these derivatives against InhA receptor revealed favorable binding interactions. Further, in silico predicted ADME properties of these compounds 4a-4h were found to be in the acceptable ranges including satisfactory Lipinski’s rule of five, thereby indicating their potential as drug-like molecules. Conclusion: In particular, the 1,4-DHP derivative 4f can be considered as an attractive lead molecule for further exploration and development of more potent anti-TB agents as InhA inhibitors.

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