scholarly journals Efflux Pump Inhibitors against Nontuberculous Mycobacteria

2020 ◽  
Vol 21 (12) ◽  
pp. 4191
Author(s):  
Laura Rindi
Keyword(s):  
Drug Resistance ◽  
Efflux Pump ◽  
Nontuberculous Mycobacteria ◽  
Current Knowledge ◽  
New Drugs ◽  
Human Pathogens ◽  
Intracellular Accumulation ◽  
Promising Strategy ◽  
Combined Use ◽  
Efflux Pump Inhibitors

Over the last years, nontuberculous mycobacteria (NTM) have emerged as important human pathogens. Infections caused by NTM are often difficult to treat due to an intrinsic multidrug resistance for the presence of a lipid-rich outer membrane, thus encouraging an urgent need for the development of new drugs for the treatment of mycobacterial infections. Efflux pumps (EPs) are important elements that are involved in drug resistance by preventing intracellular accumulation of antibiotics. A promising strategy to decrease drug resistance is the inhibition of EP activity by EP inhibitors (EPIs), compounds that are able to increase the intracellular concentration of antimicrobials. Recently, attention has been focused on identifying EPIs in mycobacteria that could be used in combination with drugs. The aim of the present review is to provide an overview of the current knowledge on EPs and EPIs in NTM and also, the effect of potential EPIs as well as their combined use with antimycobacterial drugs in various NTM species are described.

Efflux Pump Inhibitors and Their Role in the Reversal of Drug Resistance

2019 ◽  
pp. 251-275 ◽  
Author(s):  
Samreen ◽  
Iqbal Ahmad ◽  
Faizan Abul Qais ◽  
Meenu Maheshwari ◽  
Kendra P. Rumbaugh
Keyword(s):  
Drug Resistance ◽  
Efflux Pump ◽  
Efflux Pump Inhibitors

QSAR Studies on Bacterial Efflux Pump Inhibitors

2015 ◽  
pp. 238-268 ◽  
Author(s):  
Khac-Minh Thai ◽  
Trong-Nhat Do ◽  
Thuy-Viet-Phuong Nguyen ◽  
Duc-Khanh-Tho. Nguyen ◽  
Thanh-Dao Tran
Keyword(s):  
Bacterial Resistance ◽  
Efflux Pump ◽  
Current Knowledge ◽  
Efflux Pumps ◽  
Quantitative Structure Activity Relationship ◽  
Antimicrobial Drug Resistance ◽  
Qsar Studies ◽  
Hospital Stays ◽  
Efflux Pump Inhibitors

Antimicrobial drug resistance occurs when bacteria undergo certain modifications to eliminate the effectiveness of drugs, chemicals, or other agents designed to cure infections. To date, the burden of resistance has remained one of the major clinical concerns as it renders prolonged and complicated treatments, thereby increasing the medical costs with lengthier hospital stays. Of complex causes for bacterial resistance, there has been increasing evidence that proved the significant role of efflux pumps in antibiotic resistance. Coadministration of Efflux Pump Inhibitors (EPIs) with antibiotics has been considered one of the promising ways not only to improve the efficacy but also to extend the clinical utility of existing antibiotics. This chapter begins with outlining current knowledge about bacterial efflux pumps and drug designs applied in identification of their modulating compounds. Following, the chapter addresses and provides a discussion on Quantitative Structure-Activity Relationship (QSAR) analyses in search of novel and potent efflux pump inhibitors.

scholarly journals Efflux Pump Mediated Antimicrobial Resistance by Staphylococci in Health-Related Environments: Challenges and the Quest for Inhibition

Antibiotics ◽  
2021 ◽  
Vol 10 (12) ◽  
pp. 1502
Author(s):  
Abolfazl Dashtbani-Roozbehani ◽  
Melissa H. Brown
Keyword(s):  
Antimicrobial Resistance ◽  
Antimicrobial Agents ◽  
Efflux Pump ◽  
Current Knowledge ◽  
Efflux Pumps ◽  
Multidrug Resistant ◽  
Resistance Mechanisms ◽  
Multidrug Efflux Pump ◽  
New Antibiotics ◽  
Efflux Pump Inhibitors

The increasing emergence of antimicrobial resistance in staphylococcal bacteria is a major health threat worldwide due to significant morbidity and mortality resulting from their associated hospital- or community-acquired infections. Dramatic decrease in the discovery of new antibiotics from the pharmaceutical industry coupled with increased use of sanitisers and disinfectants due to the ongoing COVID-19 pandemic can further aggravate the problem of antimicrobial resistance. Staphylococci utilise multiple mechanisms to circumvent the effects of antimicrobials. One of these resistance mechanisms is the export of antimicrobial agents through the activity of membrane-embedded multidrug efflux pump proteins. The use of efflux pump inhibitors in combination with currently approved antimicrobials is a promising strategy to potentiate their clinical efficacy against resistant strains of staphylococci, and simultaneously reduce the selection of resistant mutants. This review presents an overview of the current knowledge of staphylococcal efflux pumps, discusses their clinical impact, and summarises compounds found in the last decade from plant and synthetic origin that have the potential to be used as adjuvants to antibiotic therapy against multidrug resistant staphylococci. Critically, future high-resolution structures of staphylococcal efflux pumps could aid in design and development of safer, more target-specific and highly potent efflux pump inhibitors to progress into clinical use.

Tackling drug resistance with efflux pump inhibitors: from bacteria to cancerous cells

2019 ◽  
Vol 45 (3) ◽  
pp. 334-353 ◽  
Author(s):  
Rene Christena Lowrence ◽  
Selva Ganesan Subramaniapillai ◽  
Venkatasubramanian Ulaganathan ◽  
Saisubramanian Nagarajan
Keyword(s):  
Drug Resistance ◽  
Efflux Pump ◽  
Efflux Pump Inhibitors ◽  
Cancerous Cells

scholarly journals The Contribution of Efflux Pumps in Mycobacterium abscessus Complex Resistance to Clarithromycin

Antibiotics ◽  
2019 ◽  
Vol 8 (3) ◽  
pp. 153 ◽  
Author(s):  
Júlia S. Vianna ◽  
Diana Machado ◽  
Ivy B. Ramis ◽  
Fábia P. Silva ◽  
Dienefer V. Bierhals ◽  
...  
Keyword(s):  
Drug Resistance ◽  
Efflux Pump ◽  
Efflux Pumps ◽  
Drug Susceptibility ◽  
Drug Susceptibility Testing ◽  
Mycobacterium Abscessus ◽  
New Drugs ◽  
Clarithromycin Resistance ◽  
Mycobacterium Abscessus Complex

The basis of drug resistance in Mycobacterium abscessus is still poorly understood. Nevertheless, as seen in other microorganisms, the efflux of antimicrobials may also play a role in M. abscessus drug resistance. Here, we investigated the role of efflux pumps in clarithromycin resistance using nine clinical isolates of M. abscessus complex belonging to the T28 erm(41) sequevar responsible for the inducible resistance to clarithromycin. The strains were characterized by drug susceptibility testing in the presence/absence of the efflux inhibitor verapamil and by genetic analysis of drug-resistance-associated genes. Efflux activity was quantified by real-time fluorometry. Efflux pump gene expression was studied by RT-qPCR upon exposure to clarithromycin. Verapamil increased the susceptibility to clarithromycin from 4- to ≥64-fold. The efflux pump genes MAB_3142 and MAB_1409 were found consistently overexpressed. The results obtained demonstrate that the T28 erm(41) polymorphism is not the sole cause of the inducible clarithromycin resistance in M. abscessus subsp. abscessus or bolletii with efflux activity providing a strong contribution to clarithromycin resistance. These data highlight the need for further studies on M. abscessus efflux response to antimicrobial stress in order to implement more effective therapeutic regimens and guidance in the development of new drugs against these bacteria.

Antimicrobial Adjuvants - A Novel Approach to Manage Antimicrobial Resistance

2021 ◽  
Vol 18 (4) ◽  
pp. 315-325
Author(s):  
Chirag Patel ◽  
Sanjeev Acharya ◽  
Priyanka Patel
Keyword(s):  
Antibiotic Resistance ◽  
Efflux Pump ◽  
Health Issues ◽  
Promising Strategy ◽  
Novel Approach ◽  
New Antibiotics ◽  
Efflux Pump Inhibitors ◽  
Emergence Of Resistance ◽  
Permeability Enhancers

Antibiotic resistance is one of the most prevalent, complex and serious global health issues, and needs to be monitored and controlled with medicine. Many approaches have been used to reduce the emergence and impact of resistance to antibiotics. The antimicrobial adjuvant approach is considered as novel, more effective and less expensive. The said approach not only suppresses the emergence of resistance but also conserves the activity of existing antibiotics by offering a promising strategy that is also complementary to the discovery of new antibiotics. This review contains an outline of the basic types of antibiotic adjuvant, their structure, the basis of their operation, their substrate antibiotics and the challenges in this field, as well as the role of potential compounds, namely β-lactamase inhibitors, efflux pump inhibitors and permeability enhancers in antibiotic resistance and their possible solutions.

scholarly journals Exploring Phytochemicals for Combating Antibiotic Resistance in Microbial Pathogens

2021 ◽  
Vol 12 ◽  
Author(s):  
Tushar Khare ◽  
Uttpal Anand ◽  
Abhijit Dey ◽  
Yehuda G. Assaraf ◽  
Zhe-Sheng Chen ◽  
...  
Keyword(s):  
Drug Resistance ◽  
Antibiotic Resistance ◽  
Current Knowledge ◽  
Plant Secondary Metabolites ◽  
Agricultural Practices ◽  
Resistance Mechanisms ◽  
New Drugs ◽  
Microbial Pathogens ◽  
Drug Resistant ◽  
Microbial Drug Resistance

Antibiotic resistance or microbial drug resistance is emerging as a serious threat to human healthcare globally, and the multidrug-resistant (MDR) strains are imposing major hurdles to the progression of drug discovery programs. Newer antibiotic-resistance mechanisms in microbes contribute to the inefficacy of the existing drugs along with the prolonged illness and escalating expenditures. The injudicious usage of the conventional and commonly available antibiotics in human health, hygiene, veterinary and agricultural practices is proving to be a major driver for evolution, persistence and spread of antibiotic-resistance at a frightening rate. The drying pipeline of new and potent antibiotics is adding to the severity. Therefore, novel and effective new drugs and innovative therapies to treat MDR infections are urgently needed. Apart from the different natural and synthetic drugs being tested, plant secondary metabolites or phytochemicals are proving efficient in combating the drug-resistant strains. Various phytochemicals from classes including alkaloids, phenols, coumarins, terpenes have been successfully demonstrated their inhibitory potential against the drug-resistant pathogens. Several phytochemicals have proved effective against the molecular determinants responsible for attaining the drug resistance in pathogens like membrane proteins, biofilms, efflux pumps and bacterial cell communications. However, translational success rate needs to be improved, but the trends are encouraging. This review highlights current knowledge and developments associated challenges and future prospects for the successful application of phytochemicals in combating antibiotic resistance and the resistant microbial pathogens.

Novel Antibacterial Strategies for Combating Bacterial Multidrug Resistance

2020 ◽  
Vol 25 (44) ◽  
pp. 4717-4724
Author(s):  
Xiao-Ling Xu ◽  
Xu-Qi Kang ◽  
Jing Qi ◽  
Fei-Yang Jin ◽  
Di Liu ◽  
...  
Keyword(s):  
Drug Resistance ◽  
Multidrug Resistance ◽  
Combination Therapy ◽  
Efflux Pump ◽  
Multidrug Resistant ◽  
Multi Drug Resistance ◽  
Novel Treatments ◽  
Global Problems ◽  
Efflux Pump Inhibitors ◽  
Multidrug Resistant Pathogens

Background: Antibacterial multidrug resistance has emerged as one of the foremost global problems affecting human health. The emergence of resistant infections with the increasing number of multidrug-resistant pathogens has posed a serious problem, which required innovative collaborations across multiple disciplines to address this issue. Methods: In this review, we will explain the mechanisms of bacterial multidrug resistance and discuss different strategies for combating it, including combination therapy, the use of novel natural antibiotics, and the use of nanotechnology in the development of efflux pump inhibitors. Results: While combination therapy will remain the mainstay of bacterial multi-drug resistance treatment, nanotechnology will play critical roles in the development of novel treatments in the coming years. Conclusion: Nanotechnology provides an encouraging platform for the development of clinically relevant and practical strategies to overcome drug resistance in the future.

Sign in / Sign up

Export Citation Format

Share Document