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.

scholarly journals Antimicrobial, Anticancer and Multidrug-Resistant Reversing Activity of Novel Oxygen-, Sulfur- and Selenoflavones and Bioisosteric Analogues

2020 ◽  
Vol 13 (12) ◽  
pp. 453
Author(s):  
Małgorzata Anna Marć ◽  
Annamária Kincses ◽  
Bálint Rácz ◽  
Muhammad Jawad Nasim ◽  
Muhammad Sarfraz ◽  
...  
Keyword(s):  
Multidrug Resistance ◽  
Cancer Treatment ◽  
Efflux Pump ◽  
Multidrug Resistant ◽  
Positive Control ◽  
Biological Evaluation ◽  
Glycoprotein P ◽  
Drug Candidates ◽  
P Glycoprotein ◽  
Efflux Pump Inhibitors

Multidrug resistance of cancer cells to cytotoxic drugs still remains a major obstacle to the success of chemotherapy in cancer treatment. The development of new drug candidates which may serve as P-glycoprotein (P-gp) efflux pump inhibitors is a promising strategy. Selenium analogues of natural products, such as flavonoids, offer an interesting motif from the perspective of drug design. Herein, we report the biological evaluation of novel hybrid compounds, bearing both the flavone core (compounds 1–3) or a bioisosteric analogue core (compounds 4–6) and the triflyl functional group against Gram-positive and Gram-negative bacteria, yeasts, nematodes, and human colonic adenocarcinoma cells. Results show that these flavones and analogues of flavones inhibited the activity of multidrug resistance (MDR) efflux pump ABCB1 (P-glycoprotein, P-gp). Moreover, the results of the rhodamine 123 accumulation assay demonstrated a dose-dependent inhibition of the abovementioned efflux pump. Three compounds (4, 5, and 6) exhibited potent inhibitory activity, much stronger than the positive control, verapamil. Thus, these chalcogen bioisosteric analogues of flavones become an interesting class of compounds which could be considered as P-gp efflux pump inhibitors in the therapy of MDR cancer. Moreover, all the compounds served as promising adjuvants in the cancer treatment, since they exhibited the P-gp efflux pump modulating activity.

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.

scholarly journals Sensitizing multi drug resistant Staphylococcus aureus isolated from surgical site infections to antimicrobials by efflux pump inhibitors

2020 ◽  
Vol 20 (4) ◽  
pp. 1632-45
Author(s):  
Baiomy Amr A ◽  
Shaker Ghada H ◽  
Abbas Hisham A
Keyword(s):  
Staphylococcus Aureus ◽  
Multidrug Resistance ◽  
Ethidium Bromide ◽  
Efflux Pump ◽  
Surgical Site Infections ◽  
Efflux Pumps ◽  
Multidrug Resistant ◽  
Minor Role ◽  
Efflux Pump Inhibitors ◽  
A Minor

Background: Staphylococcus aureus is a common hospital acquired infections pathogen. Multidrug-resistant Methicillin-resist- ant Staphylococcus aureus represents a major problem in Egyptian hospitals. The over-expression of efflux pumps is a main cause of multidrug resistance. The discovery of efflux pump inhibitors may help fight multidrug resistance by sensitizing bacteria to antibiotics. This study aimed to investigate the role of efflux pumps in multidrug resistance. Methods: Twenty multidrug resistant S. aureus isolates were selected. Efflux pumps were screened by ethidium bromide agar cartwheel method and polymerase chain reaction. The efflux pump inhibition by seven agents was tested by ethidium bromide agar cartwheel method and the effect on sensitivity to selected antimicrobials was investigated by broth microdilu- tion method. Results: Seventy percent of isolates showed strong efflux activity, while 30% showed intermediate activity. The efflux genes mdeA, norB, norC, norA and sepA were found to play the major role in efflux, while genes mepA, smr and qacA/B had a minor role. Verapamil and metformin showed significant efflux inhibition and increased the sensitivity to tested antimicrobials, while vildagliptin, atorvastatin, domperidone, mebeverine and nifuroxazide showed no effect. Conclusion: Efflux pumps are involved in multidrug resistance in Staphylococcus aureus. Efflux pump inhibitors could increase the sensitivity to antimicrobials. Keywords: Staphylococcus aureus; multidrug resistance; efflux pump inhibitors.

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 Berberine Improves Chemo-Sensitivity to Cisplatin by Enhancing Cell Apoptosis and Repressing PI3K/AKT/mTOR Signaling Pathway in Gastric Cancer

2020 ◽  
Vol 11 ◽  
Author(s):  
Yingying Kou ◽  
Bending Tong ◽  
Weiqing Wu ◽  
Xiangqing Liao ◽  
Min Zhao
Keyword(s):  
Gastric Cancer ◽  
Drug Resistance ◽  
Multidrug Resistance ◽  
Cell Viability ◽  
Cancer Cells ◽  
Cell Apoptosis ◽  
Mtor Signaling ◽  
Multi Drug Resistance ◽  
Gastric Cancer Cells

Gastric cancer is one of the most common malignancies ranks as the second leading cause of cancer-related mortality in the world. Cisplatin (DDP) is commonly used for gastric cancer treatment, whereas recurrence and metastasis are common because of intrinsic and acquired DDP-resistance. The aim of this study is to examine the effects of berberine on the DDP-resistance in gastric cancer and explore the underling mechanisms. In this study, we established the DDP-resistant gastric cancer cells, where the IC50 values of DDP in the BGC-823/DDP and SGC-7901/DDP were significantly higher than that in the corresponding parental cells. Berberine could concentration-dependently inhibited the cell viability of BGC-823 and SGC-7901 cells; while the inhibitory effects of berberine on the cell viability were largely attenuated in the DDP-resistant cells. Berberine pre-treatment significantly sensitized BGC-823/DDP and SGC-7901/DDP cells to DDP. Furthermore, berberine treatment concentration-dependently down-regulated the multidrug resistance-associated protein 1 and multi-drug resistance-1 protein levels in the BGC-823/DDP and SGC7901/DDP cells. Interestingly, the cell apoptosis of BGC-823/DDP and SGC-7901/DDP cells was significantly enhanced by co-treatment with berberine and DDP. The results from animals also showed that berberine treatment sensitized SGC-7901/DDP cells to DDP in vivo. Mechanistically, berberine significantly suppressed the PI3K/AKT/mTOR in the BGC-823/DDP and SGC-7901/DDP cells treated with DDP. In conclusion, we observed that berberine sensitizes gastric cancer cells to DDP. Further mechanistic findings suggested that berberine-mediated DDP-sensitivity may be associated with reduced expression of drug transporters (multi-drug resistance-1 and multidrug resistance-associated protein 1), enhanced apoptosis and repressed PI3K/AKT/mTOR signaling.

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