scholarly journals Mechanistic Insights of Drug Resistance in Staphylococcus Aureus with Special Reference to Newer Antibiotics

2021 ◽  
Author(s):  
Atamjit Singh ◽  
Kirandeep Kaur ◽  
Pallvi Mohana ◽  
Avneet Kaur ◽  
Komalpreet Kaur ◽  
...  
Keyword(s):  
Staphylococcus Aureus ◽  
Drug Resistance ◽  
Special Reference ◽  
Healthcare System ◽  
Drug Targets ◽  
Molecular Mechanisms ◽  
Pathogenic Bacterium ◽  
Functional Behavior ◽  
Genetic Modifications ◽  
Shed Light

Staphylococcus aureus is the most ubiquitous microorganism in both environment as well as animals and exists as commensal and pathogenic bacterium. In past few years it has been emerged as a superbug causing serious burden on healthcare system. This bacterium has been found to be the most resistant one toward most of the antibiotics due to its rapid structural and genetic modifications. This chapter will shed light on various types of molecular mechanisms responsible for resistance of Staphylococcus aureus showcasing how it has been emerged as a superbug. Moreover, the recent approaches which include exploring of different drug targets keeping in view the structural and functional behavior of the Staphylococcus aureus has also been discussed.

scholarly journals MicroRNA-Based Therapeutics for Drug-Resistant Colorectal Cancer

2021 ◽  
Vol 14 (2) ◽  
pp. 136
Author(s):  
Eunsun Jung ◽  
Jinhyeon Choi ◽  
Jang-Seong Kim ◽  
Tae-Su Han
Keyword(s):  
Colorectal Cancer ◽  
Drug Resistance ◽  
Drug Targets ◽  
Molecular Mechanisms ◽  
Target Genes ◽  
Therapeutic Targets ◽  
Cell Cycle Checkpoints ◽  
Drug Uptake ◽  
Cancer Drug ◽  
Drug Resistant

Although therapeutic approaches for patients with colorectal cancer (CRC) have improved in the past decades, the problem of drug resistance still persists and acts as a major obstacle for effective therapy. Many studies have shown that drug resistance is related to reduced drug uptake, modification of drug targets, and/or transformation of cell cycle checkpoints. A growing body of evidence indicates that several microRNAs (miRNAs) may contribute to the drug resistance to chemotherapy, targeted therapy, and immunotherapy by regulating the drug resistance-related target genes in CRC. These drug resistance-related miRNAs may be used as promising biomarkers for predicting drug response or as potential therapeutic targets for treating patients with CRC. In this review, we summarized the recent discoveries regarding anti-cancer drug-related miRNAs and their molecular mechanisms in CRC. Furthermore, we discussed the challenges associated with the clinical application of miRNAs as biomarkers for the diagnosis of drug-resistant patients and as therapeutic targets for CRC treatment.

scholarly journals The LABCG2 Transporter from the Protozoan Parasite Leishmania Is Involved in Antimony Resistance

2016 ◽  
Vol 60 (6) ◽  
pp. 3489-3496 ◽  
Author(s):  
Ana Perea ◽  
José Ignacio Manzano ◽  
Santiago Castanys ◽  
Francisco Gamarro
Keyword(s):  
Drug Resistance ◽  
Plasma Membrane ◽  
Drug Targets ◽  
Molecular Mechanisms ◽  
Leishmania Major ◽  
Fluorescent Protein ◽  
Protozoan Parasite ◽  
Content Type ◽  
Northern India ◽  
Antimony Resistance

Treatment for leishmaniasis, which is caused byLeishmaniaprotozoan parasites, currently relies on a reduced arsenal of drugs. However, the significant increase in the incidence of drug therapeutic failure and the growing resistance to first-line drugs like antimonials in some areas of Northern India and Nepal limit the control of this parasitic disease. Understanding the molecular mechanisms of resistance inLeishmaniais now a matter of urgency to optimize drugs used and to identify novel drug targets to block or reverse resistant mechanisms. Some members of the family of ATP-binding cassette (ABC) transporters inLeishmaniahave been associated with drug resistance. In this study, we have focused our interest to characterize LABCG2's involvement in drug resistance inLeishmania. Leishmania majorparasites overexpressing the ABC protein transporter LABCG2 were generated in order to assess how LABCG2 is involved in drug resistance. Assays of susceptibility to different leishmanicidal agents were carried out. Analysis of the drug resistance profile revealed thatLeishmaniaparasites overexpressing LABCG2 were resistant to antimony, as they demonstrated a reduced accumulation of SbIIIdue to an increase in drug efflux. Additionally, LABCG2 was able to transport thiols in the presence of SbIII. Biotinylation assays using parasites expressing LABCG2 fused with an N-terminal green fluorescent protein tag revealed that LABCG2 is partially localized in the plasma membrane; this supports data from previous studies which suggested that LABCG2 is localized in intracellular vesicles that fuse with the plasma membrane during exocytosis. In conclusion,LeishmaniaLABCG2 probably confers antimony resistance by sequestering metal-thiol conjugates within vesicles and through further exocytosis by means of the parasite's flagellar pocket.

Drug Targets and Molecular Mechanisms of Drug Resistance in Chronic Hepatitis B

2007 ◽  
Vol 132 (4) ◽  
pp. 1574-1585 ◽  
Author(s):  
Marc Ghany ◽  
T. Jake Liang
Keyword(s):  
Drug Resistance ◽  
Chronic Hepatitis ◽  
Hepatitis B ◽  
Chronic Hepatitis B ◽  
Drug Targets ◽  
Molecular Mechanisms

scholarly journals Chronic Staphylococcus aureus lung infection correlates with proteogenomic and metabolic adaptations leading to an increased intracellular persistence

2018 ◽  
Author(s):  
Xin Tan ◽  
Mathieu Coureuil ◽  
Elodie Ramond ◽  
Daniel Euphrasie ◽  
Marion Dupuis ◽  
...  
Keyword(s):  
Cystic Fibrosis ◽  
Staphylococcus Aureus ◽  
Molecular Mechanisms ◽  
Expression Profiles ◽  
Lung Infection ◽  
Genetic Modifications ◽  
Protein Expression Profiles ◽  
First Time ◽  
Chronic Lung Infection

AbstractBackgroundChronic lung infection of cystic fibrosis (CF) patients by Staphylococcus aureus is a well-established epidemiological fact. Indeed, S. aureus is the most commonly identified pathogen in the lungs of CF patients. Strikingly the molecular mechanisms underlying S. aureus persistency are not understood.MethodsWe selected pairs of sequential S. aureus isolates from 3 patients with CF and from one patient with non-CF chronic lung disease. We used a combination of genomic, proteomic and metabolomic approaches with functional assays for in-depth characterization of S. aureus long-term persistence.ResultsFor the first time, we show that late S. aureus isolates from CF patients have an increased ability for intracellular survival in CFBE-F508del cells compared to ancestral early isolates. Importantly, the increased ability to persist intracellularly was confirmed for S. aureus isolates within the own patient F508del epithelial cells. An increased ability to form biofilm was also demonstrated.Furthermore, we identified the underlying genetic modifications inducing altered protein expression profiles and notable metabolic changes. These modifications affect several metabolic pathways and virulence regulators that could constitute therapeutic targets.ConclusionsOur results strongly suggest that the intracellular environment might constitute an important niche of persistence and relapse necessitating adapted antibiotic treatments.SummaryS. aureus persists for years in the lungs of patients with cystic fibrosis despite antibiotic therapies. We demonstrate that S. aureus adaptation leads to increased intracellular persistence suggesting a key role for intracellular niche during S. aureus chronic lung infection.

Anti-evolution Drugs: A New Paradigm to Combat Drug Resistance

2021 ◽  
Vol 18 ◽  
Author(s):  
Ramalingam Peraman ◽  
Santhivardhan Chinni ◽  
Sathish Kumar Sure ◽  
Vinay Kumar Kutagulla ◽  
Muthukumaran Peraman ◽  
...  
Keyword(s):  
Drug Resistance ◽  
Drug Targets ◽  
Molecular Mechanisms ◽  
Current Knowledge ◽  
Analytical Techniques ◽  
New Drugs ◽  
New Paradigm ◽  
Rate Of Increase ◽  
Antibiotic Drug ◽  
Modern Genomic

: The drug resistance confronts chemotherapy of neoplasm and microbial infections. A vast array of molecular mechanisms was implicated in drug resistance, including, generation of drug efflux transporters, mutation of drug targets, and alteration of drug metabolism. With the alarming rate of increase in drug resistance, pathogens are bolstering in such a way that many new drugs face efficacy problems within a short span of entry into the market. Evolution is the driving force towards the development of drug resistance. By adopting the modern genomic and functionomic analytical techniques, scientists have now identified novel genes and signalling proteins involved in the evolution of drug resistance in microorganisms. Given the current knowledge of bacterial evolution, the antibiotic drug discovery is ready for a paradigm shift to explore the newer ways to tackle drug resistance. The article discusses such recent developments and reviews their merits and demerits in an attempt to envisage the findings in this new domain of medicine.

E6 and E7 oncoproteins: Potential targets of cervical cancer

2020 ◽  
Vol 27 ◽  
Author(s):  
Ramarao Malla ◽  
Mohammad Amjad Kamal
Keyword(s):  
Cervical Cancer ◽  
Drug Resistance ◽  
Host Cell ◽  
Molecular Mechanisms ◽  
Immune Therapy ◽  
Cervical Lesions ◽  
Diagnostic Strategies ◽  
E6 And E7 Oncoproteins ◽  
E6 And E7

: Cervical cancer (CC) is the fourth leading cancer in women in the age group 15-44 globally. Experimental as well as epidemiological studies identified that type16 and 18 HPV cause 70% of precancerous cervical lesions as well as cervical cancer worldwide by bringing about genetic as well as epigenetic changes in the host genome. The insertion of the HPV genome triggers various defense mechanisms including the silencing of tumor suppressor genes as well as activation of oncogenes associated with cancer metastatic pathway. E6 and E7 are small oncoproteins consisting of 150 and 100 amino acids respectively. These oncoproteins affect the regulation of the host cell cycle by interfering with p53 and pRb. Further these oncoproteins adversely affect the normal functions of the host cell by binding to their signaling proteins. Recent studies demonstrated that E6 and E7 oncoproteins are potential targets for CC. Therefore, this review discusses the role of E6 and E7 oncoproteins in metastasis and drug resistance as well as their regulation, early oncogene mediated signaling pathways. This review also uncovers the recent updates on molecular mechanisms of E6 and E7 mediated phytotherapy, gene therapy, immune therapy, and vaccine strategies as well as diagnosis through precision testing. Therefore, understanding the potential role of E6/E7 in metastasis and drug resistance along with targeted treatment, vaccine, and precision diagnostic strategies could be useful for the prevention and treatment of cervical cancer.

Genetic and Epigenetic Modulation of Drug Resistance in Cancer: Challenges and Opportunities

2020 ◽  
Vol 20 (14) ◽  
pp. 1114-1131 ◽  
Author(s):  
Kanisha Shah ◽  
Rakesh M. Rawal
Keyword(s):  
Drug Resistance ◽  
Drug Targets ◽  
Complex Disease ◽  
Cancer Therapies ◽  
Altered Expression ◽  
Acquired Drug Resistance ◽  
Challenges And Opportunities ◽  
Chemotherapeutic Treatment ◽  
Epigenetic Modulation ◽  
Targeted Drug Therapies

Cancer is a complex disease that has the ability to develop resistance to traditional therapies. The current chemotherapeutic treatment has become increasingly sophisticated, yet it is not 100% effective against disseminated tumours. Anticancer drugs resistance is an intricate process that ascends from modifications in the drug targets suggesting the need for better targeted therapies in the therapeutic arsenal. Advances in the modern techniques such as DNA microarray, proteomics along with the development of newer targeted drug therapies might provide better strategies to overcome drug resistance. This drug resistance in tumours can be attributed to an individual’s genetic differences, especially in tumoral somatic cells but acquired drug resistance is due to different mechanisms, such as cell death inhibition (apoptosis suppression) altered expression of drug transporters, alteration in drug metabolism epigenetic and drug targets, enhancing DNA repair and gene amplification. This review also focusses on the epigenetic modifications and microRNAs, which induce drug resistance and contributes to the formation of tumour progenitor cells that are not destroyed by conventional cancer therapies. Lastly, this review highlights different means to prevent the formation of drug resistant tumours and provides future directions for better treatment of these resistant tumours.

Identifying Alzheimer’s Disease-related miRNA Based on Semi-clustering

2019 ◽  
Vol 19 (4) ◽  
pp. 216-223 ◽  
Author(s):  
Tianyi Zhao ◽  
Donghua Wang ◽  
Yang Hu ◽  
Ningyi Zhang ◽  
Tianyi Zang ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Drug Targets ◽  
Molecular Mechanisms ◽  
Feature Vector ◽  
Mirna Gene ◽  
Interaction Network ◽  
Gene Interaction ◽  
Proteinprotein Interaction ◽  
Synaptic Structures

Background: More and more scholars are trying to use it as a specific biomarker for Alzheimer’s Disease (AD) and mild cognitive impairment (MCI). Multiple studies have indicated that miRNAs are associated with poor axonal growth and loss of synaptic structures, both of which are early events in AD. The overall loss of miRNA may be associated with aging, increasing the incidence of AD, and may also be involved in the disease through some specific molecular mechanisms. Objective: Identifying Alzheimer’s disease-related miRNA can help us find new drug targets, early diagnosis. Materials and Methods: We used genes as a bridge to connect AD and miRNAs. Firstly, proteinprotein interaction network is used to find more AD-related genes by known AD-related genes. Then, each miRNA’s correlation with these genes is obtained by miRNA-gene interaction. Finally, each miRNA could get a feature vector representing its correlation with AD. Unlike other studies, we do not generate negative samples randomly with using classification method to identify AD-related miRNAs. Here we use a semi-clustering method ‘one-class SVM’. AD-related miRNAs are considered as outliers and our aim is to identify the miRNAs that are similar to known AD-related miRNAs (outliers). Results and Conclusion: We identified 257 novel AD-related miRNAs and compare our method with SVM which is applied by generating negative samples. The AUC of our method is much higher than SVM and we did case studies to prove that our results are reliable.

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