scholarly journals Molecular Engineering of Polymyxin B for Imaging and Treatment of Bacterial Infections

2022 ◽  
Vol 9 ◽  
Author(s):  
Minghao Wu ◽  
Shipeng He ◽  
Hua Tang ◽  
Honggang Hu ◽  
Yejiao Shi

The emergence of multi-drug resistant bacteria and the lack of novel antibiotics to combat them have led to the revival of polymyxin B, a previously abandoned antibiotic due to its potential nephrotoxicity and neurotoxicity. To facilitate its widely clinical applications, increasing effort has been devoted to molecularly engineer polymyxin B for the targeted imaging and effective treatment of bacterial infections. Herein, the molecular engineering strategies will be summarized in this mini review, with selected recent advances for illustration. Perspective of the challenges and trends in this exciting and eagerly anticipated research area will also be provided in the end. We hope this mini review will inspire researchers from diverse fields to bring forward the next wave of exploiting molecular engineering approaches to propel the “old” polymyxin B to “new” clinical significance in combating bacterial infections.

Author(s):  
E.A. Martis ◽  
G M Doshi ◽  
G V Aggarwal ◽  
P P Shanbhag

With the emergence of newer diseases, resistant forms of infectious diseases and multi-drug resistant bacteria, it has become essential to develop novel and more effective antibiotics. Current antibiotics are obtained from terrestrial life or made synthetically from intermediates. The ocean represents virtually untapped resource from which novel antibiotic compounds can be discovered. It is the marine world that will provide the pharmaceutical industry with the next generation of antibiotics. Marine antibiotics are antibiotics obtained from marine organisms. Scientists have reported the discovery of various antibiotics from marine bacteria (aplasmomycin, himalomycins, and pelagiomycins), sponges (Ara C, variabillin, strobilin, ircinin-1, aeroplysin, 3,5-dibromo-4-hydroxyphenylacetamide), coelenterates (asperidol and eunicin), mollusks (laurinterol and pachydictyol), tunicates (geranylhydroquinone and cystadytins), algae (cycloeudesmol, aeroplysinin-1(+), prepacifenol and tetrabromoheptanone), worms (tholepin and 3,5-dibromo-4-hydroxybezaldehyde), and actinomycetes (marinomycins C and D). This indicates that the marine environment, representing approximately half of the global diversity, is an enormous resource for new antibiotics and this source needs to be explored for the discovery of new generation antibiotics. The present article provides an overview of various antibiotics obtained from marine sources.


Author(s):  
Daniel Berman

How can we prevent the rise of resistance to antibiotics? In this video, Daniel Berman,  Nesta Challenges, discusses the global threat of AMR and how prizes like the Longitude Prize can foster the development of rapid diagnostic tests for bacterial infections, helping to contribute towards reducing the global threat of drug resistant bacteria. Daniel outlines how accelerating the development of rapid point-of-care tests will ensure that bacterial infections are treated with the most appropriate antibiotic, at the right time and in the right healthcare setting.


2020 ◽  
Vol 8 (18) ◽  
pp. 4975-4996
Author(s):  
Pengfei Zou ◽  
Wen-Ting Chen ◽  
Tongyi Sun ◽  
Yuanyuan Gao ◽  
Li-Li Li ◽  
...  

Bacterial infections, especially the refractory treatment of drug-resistant bacteria, are one of the greatest threats to human health. Self-assembling peptide-based strategies can specifically detect the bacteria at the site of infection in the body and kill it.


Molecules ◽  
2020 ◽  
Vol 25 (7) ◽  
pp. 1543 ◽  
Author(s):  
Buthaina Jubeh ◽  
Zeinab Breijyeh ◽  
Rafik Karaman

Bacterial resistance to present antibiotics is emerging at a high pace that makes the development of new treatments a must. At the same time, the development of novel antibiotics for resistant bacteria is a slow-paced process. Amid the massive need for new drug treatments to combat resistance, time and effort preserving approaches, like the prodrug approach, are most needed. Prodrugs are pharmacologically inactive entities of active drugs that undergo biotransformation before eliciting their pharmacological effects. A prodrug strategy can be used to revive drugs discarded due to a lack of appropriate pharmacokinetic and drug-like properties, or high host toxicity. A special advantage of the use of the prodrug approach in the era of bacterial resistance is targeting resistant bacteria by developing prodrugs that require bacterium-specific enzymes to release the active drug. In this article, we review the up-to-date implementation of prodrugs to develop medications that are active against drug-resistant bacteria.


2013 ◽  
Vol 2013 ◽  
pp. 1-4 ◽  
Author(s):  
Junaid Iqbal ◽  
Ruqaiyyah Siddiqui ◽  
Shahana Urooj Kazmi ◽  
Naveed Ahmed Khan

Antibiotic resistance continues to pose a significant problem in the management of bacterial infections, despite advances in antimicrobial chemotherapy and supportive care. Here, we suggest a simple, inexpensive, and easy-to-perform assay to screen antimicrobial compounds from natural products or synthetic chemical libraries for their potential to work in tandem with the available antibiotics against multiple drug-resistant bacteria. The aqueous extract ofJuglans regiatree bark was tested against representative multiple drug-resistant bacteria in the aforementioned assay to determine whether it potentiates the activity of selected antibiotics. The aqueous extract ofJ. regiabark was added to Mueller-Hinton agar, followed by a lawn of multiple drug-resistant bacteria,Salmonella typhior enteropathogenicE. coli. Next, filter paper discs impregnated with different classes of antibiotics were placed on the agar surface. Bacteria incubated with extract or antibiotics alone were used as controls. The results showed a significant increase (>30%) in the zone of inhibition around the aztreonam, cefuroxime, and ampicillin discs compared with bacteria incubated with the antibiotics/extract alone. In conclusion, our assay is able to detect either synergistic or additive action ofJ. regiaextract against multiple drug-resistant bacteria when tested with a range of antibiotics.


2021 ◽  
Vol 15 (10) ◽  
pp. 2506-2511
Author(s):  
Nayyab Sultan ◽  
Sabahat Javaid Butt ◽  
Wajeeha Mehak ◽  
Samreen Qureshi ◽  
Syed Hamza Abbas ◽  
...  

Antibiotics have played a crucial role in the treatment of bacterial infections. Past few decades are marked with advancement of multidrug resistant (MDR) pathogens, which have endangered antibiotic’s therapeutic efficacy. Scientific world is now struggling with the crisis of MDR pathogens. This supreme matter demands careful attention or otherwise it would jeopardize clinical management of infectious diseases. Implication of alternative approaches can pave a new way in the treatment of these troublesome bacteria. Tea leaves are known to pose antibacterial activity against many pathogenic microorganisms. This review has summarized the antibacterial potential of tea leave’s extracts against resistant bacterial pathogens such as Staphylococcus aureus, Pseudomonas aeruginosa, Helicobacter pylori, Escherichia coli, Klebsiella pneumonia, Salmonella typhi, Acenitobacter spp, Campylobacter spp. Consumption of natural products such as tea may very well replace, minimize or obliterate this complicated situation. Keywords: Anti-bacterial, Tea, Camellia sinensis, Drug resistant bacteria, Antibiotic resistant bacteria, Synergism, Polyphenols.


2020 ◽  
Vol 64 (12) ◽  
Author(s):  
Jitender Yadav ◽  
Sana Ismaeel ◽  
Ayub Qadri

ABSTRACT Polymyxin B, used to treat infections caused by antibiotic-resistant Gram-negative bacteria, produces nephrotoxicity at its current dosage. We show that a combination of nonbactericidal concentration of this drug and lysophosphatidylcholine (LPC) potently inhibits growth of Salmonella and at least two other Gram-negative bacteria in vitro. This combination makes bacterial membrane porous and causes degradation of DnaK, the regulator of protein folding. Polymyxin B-LPC combination may be an effective and safer regimen against drug-resistant bacteria.


2020 ◽  
Vol 15 ◽  
Author(s):  
Jan H. Beumera ◽  
Jianxia Guo ◽  
Evan C. Ray ◽  
Jonas Scemama ◽  
Robert A. Parise ◽  
...  

Background: To address multidrug resistance we developed engineered cationic antimicrobial peptides (eCAPs). Lead eCAP WLBU2 displays potent activity against drug-resistant bacteria and effectively treats lethal bacterial infections in mice reducing bacterial loads to undetectable levels in diverse organs. Background: To address multidrug resistance we developed engineered cationic antimicrobial peptides (eCAPs). Lead eCAP WLBU2 displays potent activity against drug-resistant bacteria and effectively treats lethal bacterial infections in mice reducing bacterial loads to undetectable levels in diverse organs. Objective: To support development of WLBU2, we conducted a mass balance study. Methods: CD1 mice were administered 10, 15, 20 and 30 mg/kg QDx5 WLBU2 or a single dose of [14C]-WLBU2 at 15 mg/kg IV. Tolerability, tissue distribution and excretion were evaluated with liquid scintillation and HPLCradiochromatography. Results: The maximum tolerated dose of WLBU2 is 20 mg/kg IV. We could account for greater than >96% of the radioactivity distributed within mouse tissues at 5 and 15 min. By 24 h, only ~40-50% of radioactivity remained in the mice. The greatest % of the dose was present in liver, accounting for ~35% of radioactivity at 5 and 15 min, and ~ 8% of radioactivity remained at 24 h. High radioactivity was also present in kidneys, plasma, red blood cells and lungs, while less than 0.2% of radioactivity was present in brain, fat, or skeletal muscle. Urinary and fecal excretion accounted for 12.5 and 2.2% of radioactivity at 24 h. Conclusion: WLBU2 distributes widely to mouse tissues and is rapidly cleared with a terminal radioactivity half-life of 22 h, a clearance of 27.4 mL/h/kg, and a distribution volume of 0.94 L/kg. At 2-100 µg-eq/g, the concentrations of 14CWLBU2 appear high enough in the tissues to account for inhibition of microbial growth.


2017 ◽  
Vol 69 (1) ◽  
pp. 29
Author(s):  
Sanghamitra Padhi

<p class="ABS">The world has seen the emergence of many micro-organisms in the recent past which can curb the human population with their newly built genetic make-up. The latest addition to this list of panic creating organisms is, bacteria encoding the gene for New Delhi metallo-beta-lactamase (NDM)-1. NDM-1 is an enzyme that can hydrolyse and inactivate carbapenems, which are used as a last resort for the treatment of multiresistant bacterial infections. Name of these bacteria were not found in the medical literature before December 2009, because of which it can take the credit of becoming a powerful emerging bacteria which are difficult to treat. Besides <span class="Italic">Escherichia</span><span class="CharOverride-2"> </span><span class="Italic">coli</span> and <span class="BoldItalic CharOverride-2">Klebsiella pneumoniae</span>, other bacterial strains have also expressed the gene for NDM-1, which are detected in many countries.</p><div> </div>


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