scholarly journals Mass Balance Study of the Engineered Cationic Antimicrobial Peptide, WLBU2, Following a Single Intravenous Dose of 14C-WLBU2 in Mice.

2020 ◽  
Vol 15 ◽  
Author(s):  
Jan H. Beumera ◽  
Jianxia Guo ◽  
Evan C. Ray ◽  
Jonas Scemama ◽  
Robert A. Parise ◽  
...  
Keyword(s):  
Multidrug Resistance ◽  
Antimicrobial Peptides ◽  
Mass Balance ◽  
Bacterial Infections ◽  
Resistant Bacteria ◽  
Drug Resistant ◽  
Balance Study ◽  
Drug Resistant Bacteria ◽  
Mouse Tissues ◽  
Mass Balance Study

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.

Re-challenging antibiotic resistance with Daniel Berman

2020 ◽  
Author(s):  
Daniel Berman
Keyword(s):  
Bacterial Infections ◽  
Point Of Care ◽  
Healthcare Setting ◽  
Rapid Diagnostic Tests ◽  
Resistant Bacteria ◽  
Drug Resistant ◽  
Drug Resistant Bacteria ◽  
Global Threat ◽  
The Right ◽  
Point Of Care Tests

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.

scholarly journals Nanoparticles Enable Efficient Delivery of Antimicrobial Peptides for the Treatment of Deep Infections

2021 ◽  
Author(s):  
Yingxue Deng ◽  
Rui Huang ◽  
Songyin Huang ◽  
Menghua Xiong
Keyword(s):  
Antimicrobial Peptides ◽  
Broad Spectrum ◽  
Antimicrobial Properties ◽  
Therapeutic Index ◽  
Resistant Bacteria ◽  
Drug Resistant ◽  
Drug Resistant Bacteria ◽  
Efficient Delivery ◽  
Delivery Vehicles

Antimicrobial peptides (AMPs) have emerged as promising alternatives of traditional antibiotics against drug-resistant bacteria owing to their broad-spectrum antimicrobial properties and low tendency to drugresistance. However, their therapeutic efficacy in vivo, especially for infections in deep organs, is limited owing to their systemic toxicity and low bioavailability. Nanoparticles-based delivery systems offer a strategy to increase the therapeutic index of AMPs by preventing proteolysis, increasing the accumulation at infection sites, and reducing toxicity. Herein, we will discuss the current progress of using nanoparticles as delivery vehicles for AMPs for the treatment of deep infections.

scholarly journals Design, Engineering and Discovery of Novel α-Helical and β-Boomerang Antimicrobial Peptides against Drug Resistant Bacteria

2020 ◽  
Vol 21 (16) ◽  
pp. 5773 ◽  
Author(s):  
Surajit Bhattacharjya ◽  
Suzana K. Straus
Keyword(s):  
Antimicrobial Peptides ◽  
Resistant Bacteria ◽  
Drug Resistant ◽  
Antibiotic Development ◽  
Extensively Drug Resistant ◽  
Drug Resistant Bacteria ◽  
Drying Up ◽  
Further Development ◽  
Lps Binding

In an era where the pipeline of new antibiotic development is drying up, the continuous rise of multi-drug resistant (MDR) and extensively drug resistant (XDR) bacteria are genuine threats to human health. Although antimicrobial peptides (AMPs) may serve as promising leads against drug resistant bacteria, only a few AMPs are in advanced clinical trials. The limitations of AMPs, namely their low in vivo activity, toxicity, and poor bioavailability, need to be addressed. Here, we review engineering of frog derived short α-helical AMPs (aurein, temporins) and lipopolysaccharide (LPS) binding designed β-boomerang AMPs for further development. The discovery of novel cell selective AMPs from the human proprotein convertase furin is also discussed.

Recent advances: peptides and self-assembled peptide-nanosystems for antimicrobial therapy and diagnosis

2020 ◽  
Vol 8 (18) ◽  
pp. 4975-4996
Author(s):  
Pengfei Zou ◽  
Wen-Ting Chen ◽  
Tongyi Sun ◽  
Yuanyuan Gao ◽  
Li-Li Li ◽  
...  
Keyword(s):  
Human Health ◽  
Antimicrobial Therapy ◽  
Bacterial Infections ◽  
The Body ◽  
Resistant Bacteria ◽  
Drug Resistant ◽  
Self Assembling ◽  
Recent Advances ◽  
Drug Resistant Bacteria ◽  
Therapy And Diagnosis

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.

scholarly journals LAMP2: a major update of the database linking antimicrobial peptides

Database ◽  
2020 ◽  
Vol 2020 ◽  
Author(s):  
Guizi Ye ◽  
Hongyu Wu ◽  
Jinjiang Huang ◽  
Wei Wang ◽  
Kuikui Ge ◽  
...  
Keyword(s):  
Antimicrobial Peptides ◽  
Primary Structure ◽  
Scientific Community ◽  
Resistant Bacteria ◽  
Drug Resistant ◽  
Current Version ◽  
Functional Activities ◽  
Drug Resistant Bacteria ◽  
Functional Classes ◽  
And Function

Abstract Antimicrobial peptides (AMPs) have been regarded as a potential weapon to fight against drug-resistant bacteria, which is threating the globe. Thus, more and more AMPs had been designed or identified. There is a need to integrate them into a platform for researchers to facilitate investigation and analyze existing AMPs. The AMP database has become an important tool for the discovery and transformation of AMPs as agents. A database linking antimicrobial peptides (LAMPs), launched in 2013, serves as a comprehensive tool to supply exhaustive information of AMP on a single platform. LAMP2, an updated version of LAMP, holds 23 253 unique AMP sequences and expands to link 16 public AMP databases. In the current version, there are more than 50% (12 236) sequences only linking a single database and more than 45% of AMPs linking two or more database links. Additionally, updated categories based on primary structure, collection, composition, source and function have been integrated into LAMP2. Peptides in LAMP2 have been integrated in 8 major functional classes and 38 functional activities. More than 89% (20 909) of the peptides are experimentally validated peptides. A total of 1924 references were extracted and regarded as the evidence for supporting AMP activity and cytotoxicity. The updated version will be helpful to the scientific community.

Folic acid-modified mesoporous silica nanoparticles with pH-responsiveness loaded with Amp for an enhanced effect against anti-drug-resistant bacteria by overcoming efflux pump systems

2018 ◽  
Vol 6 (7) ◽  
pp. 1923-1935 ◽  
Author(s):  
Xu Chen ◽  
Yanan Liu ◽  
Ange Lin ◽  
Na Huang ◽  
Liquan Long ◽  
...  
Keyword(s):  
Folic Acid ◽  
Multidrug Resistance ◽  
Mesoporous Silica ◽  
Efflux Pump ◽  
Mesoporous Silica Nanoparticles ◽  
Resistant Bacteria ◽  
Drug Resistant ◽  
Pump System ◽  
Drug Resistant Bacteria ◽  
Antibiotic Failure

Efflux pump system-mediated bacterial multidrug resistance is one of the main causes of antibiotic failure.

scholarly journals A Simple Assay to Screen Antimicrobial Compounds Potentiating the Activity of Current Antibiotics

2013 ◽  
Vol 2013 ◽  
pp. 1-4 ◽  
Author(s):  
Junaid Iqbal ◽  
Ruqaiyyah Siddiqui ◽  
Shahana Urooj Kazmi ◽  
Naveed Ahmed Khan
Keyword(s):  
Aqueous Extract ◽  
Bacterial Infections ◽  
Juglans Regia ◽  
Tree Bark ◽  
Resistant Bacteria ◽  
Multiple Drug ◽  
Drug Resistant ◽  
Antimicrobial Compounds ◽  
Drug Resistant Bacteria ◽  
Multiple Drug Resistant

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.

Tea: An anti-bacterial agent against drug resistant bacteria

2021 ◽  
Vol 15 (10) ◽  
pp. 2506-2511
Author(s):  
Nayyab Sultan ◽  
Sabahat Javaid Butt ◽  
Wajeeha Mehak ◽  
Samreen Qureshi ◽  
Syed Hamza Abbas ◽  
...  
Keyword(s):  
Bacterial Infections ◽  
Salmonella Typhi ◽  
Multidrug Resistant ◽  
Resistant Bacteria ◽  
Klebsiella Pneumonia ◽  
Drug Resistant ◽  
Antibiotic Resistant ◽  
Bacterial Agent ◽  
Drug Resistant Bacteria ◽  
Scientific World

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.

scholarly journals New Delhi metallo-beta-lactamase-1: A weapon for the newly emerging drug-resistant bacteria

2017 ◽  
Vol 69 (1) ◽  
pp. 29
Author(s):  
Sanghamitra Padhi
Keyword(s):  
Bacterial Infections ◽  
Medical Literature ◽  
Resistant Bacteria ◽  
New Delhi ◽  
Beta Lactamase ◽  
Drug Resistant ◽  
Recent Past ◽  
Bacterial Strains ◽  
Drug Resistant Bacteria ◽  
Micro Organisms

<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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