Use of Efflux Pump Inhibitors (EPIs) to overcome bacterial Multi-Drug Resistance (MDR): plants as a source of chemodiversity and their adaptive response toward bacterial stress

Planta Medica ◽  
2008 ◽  
Vol 74 (09) ◽  
Author(s):  
S Michalet ◽  
AM Mariotte ◽  
S Gibbons ◽  
MG Dijoux-Franca
Keyword(s):  
Drug Resistance ◽  
Adaptive Response ◽  
Efflux Pump ◽  
Multi Drug Resistance ◽  
Efflux Pump Inhibitors

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.

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

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.

scholarly journals Impact of an Intervention to Control Imipenem-Resistant Acinetobacter baumannii and Its Resistance Mechanisms: An 8-Year Survey

2021 ◽  
Vol 11 ◽  
Author(s):  
Lida Chen ◽  
Pinghai Tan ◽  
Jianming Zeng ◽  
Xuegao Yu ◽  
Yimei Cai ◽  
...  
Keyword(s):  
Drug Resistance ◽  
Acinetobacter Baumannii ◽  
Bacterial Resistance ◽  
Efflux Pump ◽  
Resistance Mechanism ◽  
Resistance Mechanisms ◽  
Multi Drug Resistance ◽  
Minimal Inhibitory Concentrations ◽  
Resistance Rates ◽  
The Impact

BackgroundThis study aimed to examine the impact of an intervention carried out in 2011 to combat multi-drug resistance and outbreaks of imipenem-resistant Acinetobacter baumannii (IRAB), and to explore its resistance mechanism.MethodsA total of 2572 isolates of A. baumannii, including 1673 IRAB isolates, were collected between 2007 and 2014. An intervention was implemented to control A. baumannii resistance and outbreaks. Antimicrobial susceptibility was tested by calculating minimal inhibitory concentrations (MICs), and outbreaks were typed using pulsed-field gel electrophoresis (PFGE). Resistance mechanisms were explored by polymerase chain reaction (PCR) and whole genome sequencing (WGS).ResultsFollowing the intervention in 2011, the resistance rates of A. baumannii to almost all tested antibiotics decreased, from 85.3 to 72.6% for imipenem, 100 to 80.8% for ceftriaxone, and 45.0 to 6.9% for tigecycline. The intervention resulted in a decrease in the number (seven to five), duration (8–3 months), and departments (five to three) affected by outbreaks; no outbreaks occurred in 2011. After the intervention, only blaAMPC (76.47 to 100%) and blaTEM–1 (75.74 to 96.92%) increased (P < 0.0001); whereas blaGES–1 (32.35 to 3.07%), blaPER–1 (21.32 to 1.54%), blaOXA–58 (60.29 to 1.54%), carO (37.50 to 7.69%), and adeB (9.56 to 3.08%) decreased (P < 0.0001). Interestingly, the frequency of class B β-lactamase genes decreased from 91.18% (blaSPM–1) and 61.03% (blaIMP–1) to 0%, while that of class D blaOXA–23 increased to 96.92% (P < 0.0001). WGS showed that the major PFGE types causing outbreaks each year (type 01, 11, 18, 23, 26, and 31) carried the same resistance genes (blaKPC–1, blaADC–25, blaOXA–66, and adeABC), AdeR-S mutations (G186V and A136V), and a partially blocked porin channel CarO. Meanwhile, plasmids harboring blaOXA–23 were found after the intervention.ConclusionThe intervention was highly effective in reducing multi-drug resistance of A. baumannii and IRAB outbreaks in the long term. The resistance mechanisms of IRAB may involve genes encoding β-lactamases, efflux pump overexpression, outer membrane porin blockade, and plasmids; in particular, clonal spread of blaOXA–23 was the major cause of outbreaks. Similar interventions may also help reduce bacterial resistance rates and outbreaks in other hospitals.

scholarly journals High resolution melting analysis and detection of Leishmania resistance: the role of multi drug resistance 1 gene

2021 ◽  
Vol 43 (1) ◽  
Author(s):  
Maryam Fekri Soofi Abadi ◽  
Alireza Moradabadi ◽  
Reza Vahidi ◽  
Saeedeh Shojaeepour ◽  
Sara Rostami ◽  
...  
Keyword(s):  
Drug Resistance ◽  
High Resolution ◽  
High Resolution Melting ◽  
Efflux Pump ◽  
Mdr1 Gene ◽  
Multi Drug Resistance ◽  
Sequencing Method ◽  
Melting Analysis ◽  
Resistance Protein

Abstract Background Pentavalent antimonial compounds are currently used to treat leishmaniasis and resistance to these drugs is a serious problem. Multidrug resistance protein is an efflux pump of the cell membrane that expels foreign compounds. This study designed to evaluate the mutations in the multi-drug resistance 1 (MDR1) gene, in biopsy specimens of Leishmania tropica, with high resolution melting (HRM) method. In this experimental study, genomic DNA was extracted from 130 patients with skin leishmaniasis. Then, nucleotide changes were investigated throughout the gene using HRM and sequencing methods. The samples categorized in 5 groups by differences in the melting temperature (Tm). Result The nucleotide changes analysis showed that 61% of the samples of different groups that were unresponsive to drug had mutations in the MDR1 gene, which were also confirmed by the sequencing method. These mutations can be one of the factors responsible for non-responsiveness to the treatment. Conclusion According to the findings, it seems that mutation in MDR1 gene could be responsible for drug resistance to pentavalent antimonial compounds. Furthermore, HRM method can be used to diagnose drug resistance in leishmaniasis. It is also recommended that further studies be done regarding the importance of drug resistance in the leishmania affected patients.

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

Multidrug-resistant P-glycoprotein assembly revealed by Tariquidar-probe’s super-resolution imaging

Nanoscale ◽  
2021 ◽  
Author(s):  
Hongda Wang ◽  
Junling Chen ◽  
Hongru Li ◽  
Qiang Wu ◽  
Tan Zhao ◽  
...  
Keyword(s):  
Molecular Structure ◽  
Drug Resistance ◽  
Protein Expression ◽  
Efflux Pump ◽  
Super Resolution ◽  
Cell Types ◽  
Multidrug Resistant ◽  
Multi Drug Resistance ◽  
P Glycoprotein ◽  
Resolution Imaging

As an efflux pump, P-glycoproteins (P-gps) are over-expressed in many cancer cell types to confer them multi-drug resistance. Many studies have focused on elucidating its molecular structure or protein expression;...

scholarly journals Bifunctional enzyme SpoT is involved in biofilm formation of Helicobacter pylori with multidrug resistance by upregulating efflux pump Hp1174 (gluP)

2018 ◽  
Author(s):  
Xiaoran Ge ◽  
Yuying Cai ◽  
Zhenghong Chen ◽  
Sizhe Gao ◽  
Xiwen Geng ◽  
...  
Keyword(s):  
Drug Resistance ◽  
Helicobacter Pylori ◽  
Multidrug Resistance ◽  
Biofilm Formation ◽  
Efflux Pump ◽  
Efflux Pumps ◽  
Multi Drug Resistance ◽  
Bifunctional Enzyme ◽  
Average Expression Level ◽  
H Pylori

ABSTRACTThe drug resistance of Helicobacter pylori (H. pylori) is gradually becoming a serious problem. Biofilm formation is an important factor that leads to multidrug resistance in bacteria. The ability of H. pylori to form biofilms on the gastric mucosa has been known. However, there are few studies on the regulation mechanisms of H. pylori biofilm formation and multidrug resistance. Guanosine 3’-diphosphate 5’-triphosphate and guanosine 3’,5’-bispyrophosphate [(p)ppGpp] are global regulatory factors and are synthesized in H. pylori by the bifunctional enzyme SpoT. It has been reported that (p)ppGpp is involved in the biofilm formation and multidrug resistance of various bacteria. In this study, we found that SpoT also plays an important role in H. pylori biofilm formation and multidrug resistance. Therefore, it is necessary to carry out some further studies regarding its regulatory mechanism. Considering that efflux pumps are of great importance in the biofilm formation and multidrug resistance of bacteria, we tried to find if efflux pumps controlled by SpoT participate in these activities. Then, we found that Hp1174 (glucose/galactose transporter, gluP), an efflux pump of the MFS family, is highly expressed in biofilm-forming and multi-drug resistance (MDR) H. pylori and is upregulated by SpoT. Through further research, we determined that gluP involved in H. pylori biofilm formation and multidrug resistance. Furthermore, the average expression level of gluP in clinical MDR strains was considerably higher than that in clinical drug-sensitive strains. Taken together, our results revealed a novel molecular mechanism of H. pylori tolerance to multidrug.

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