scholarly journals Anti-biofilm efficacy of a medieval treatment for bacterial infection requires the combination of multiple ingredients

2020 ◽  
Author(s):  
Jessica Furner-Pardoe ◽  
Blessing O Anonye ◽  
Ricky Cain ◽  
John Moat ◽  
Catherine A. Ortori ◽  
...  
Keyword(s):  
Natural Products ◽  
Staphylococcus Epidermidis ◽  
Bacterial Biofilm ◽  
New Drugs ◽  
Resistant Bacteria ◽  
Planktonic Cells ◽  
Planktonic Bacteria ◽  
Drug Resistant Bacteria ◽  
Materials Used ◽  
Antibiotic Discovery

AbstractNovel antimicrobials are urgently needed to combat the increasing occurrence of drug-resistant bacteria and to overcome the inherent difficulties in treating biofilm-associated infections. Research into natural antimicrobials could provide candidates to fill the antibiotic discovery gap, and the study of plants and other natural materials used in historical infection remedies may enable further discoveries of natural products with useful antimicrobial activity. We previously reconstructed a 1,000-year-old remedy containing onion, garlic, wine, and bile salts, which is known as ‘Bald’s eyesalve’, and showed it to have promising antibacterial activity. In this paper, we have found this remedy has bactericidal activity against a range of Gram-negative and Gram-positive wound pathogens in planktonic culture and, crucially, that this activity is maintained against Acinetobacter baumannii, Stenotrophomonas maltophilia, Staphylococcus aureus, Staphylococcus epidermidis and Streptococcus pyogenes in a model of soft-tissue wound biofilm. While the presence of garlic in the mixture is sufficient to explain activity against planktonic cultures, garlic alone has no activity against biofilms. We have found the potent anti-biofilm activity of Bald’s eyesalve cannot be attributed to a single ingredient and requires the combination of all ingredients to achieve full activity. Our work highlights the need to explore not only single compounds but also mixtures of natural products for treating biofilm infections. These results also underline the importance of working with biofilm models when exploring natural products for the anti-biofilm pipeline.ImportanceBacteria can live in two ways, as individual planktonic cells or as a multicellular biofilm. Biofilm helps protect bacteria from antibiotics and makes them much harder to treat. Both the biofilm lifestyle and the evolution of antibiotic resistance mean we urgently need new drugs to treat infections. Here, we show that a medieval remedy made from onion, garlic, wine, and bile can kill a range of problematic bacteria grown both planktonically and as biofilms. A single component of the remedy – allicin, derived from garlic – is sufficient to kill planktonic bacteria. However, garlic or allicin alone do nothing against bacteria when they form a biofilm. All four ingredients are needed to fully kill bacterial biofilm communities, hinting that these ingredients work together to kill the bacteria. This suggests that future discovery of antibiotics from natural products could be enhanced by studying combinations of ingredients, rather than single plants or compounds.

Leveraging Novel and Existing Pathways to Approve New Therapeutics to Treat Serious Drug-Resistant Infections

2016 ◽  
Vol 42 (2-3) ◽  
pp. 429-450 ◽  
Author(s):  
Thomas J. Hwang ◽  
Aaron S. Kesselheim
Keyword(s):  
New Drugs ◽  
Resistant Bacteria ◽  
Drug Resistant ◽  
Regulatory Pathways ◽  
Medical Needs ◽  
The Past ◽  
Drug Resistant Bacteria ◽  
Patient Health ◽  
Life Threatening ◽  
Unmet Medical Needs

Accelerating the development and approval of novel therapeutics has emerged as a key public health priority given the mortality, morbidity, and economic costs associated with infections caused by drug-resistant bacteria. However, there is limited empirical evidence to guide policymaking, such as the factors that may disadvantage antibiotics compared to other classes of drugs. In this Article, we empirically examine characteristics of the key clinical trials underpinning FDA's approval of antibiotics and other drugs over the past decade. Despite perceptions that antibiotic trials are larger and more difficult to conduct, we find that antibiotic trials are no larger than those conducted for drugs approved in other disease areas with high unmet medical needs, suggesting that policymakers may need to target other levers to meaningfully stimulate innovation. We discuss the risks and benefits of harnessing new and existing regulatory pathways to speed the approval of new drugs, particularly those intended to treat patients with serious and life-threatening infections, and we evaluate ways that proposals for new regulatory pathways could be improved to better prioritize and expedite the approval of therapies with the greatest potential for patient health benefits.

Something old, something new: revisiting natural products in antibiotic drug discovery

2014 ◽  
Vol 60 (3) ◽  
pp. 147-154 ◽  
Author(s):  
Gerard D. Wright
Keyword(s):  
Natural Products ◽  
New Drugs ◽  
Clinical Use ◽  
Antibiotic Resistant ◽  
Antibiotic Drug ◽  
New Antibiotics ◽  
Bacteria And Fungi ◽  
Antibiotic Discovery ◽  
Novel Drug ◽  
New Strategies

Antibiotic discovery is in crisis. Despite a growing need for new drugs resulting from the increasing number of multi-antibiotic-resistant pathogens, there have been only a handful of new antibiotics approved for clinical use in the past 2 decades. Faced with scientific, economic, and regulatory challenges, the pharmaceutical sector seems unable to respond to what has been called an “apocalyptic” threat. Natural products produced by bacteria and fungi are genetically encoded products of natural selection that have been the mainstay sources of the antibiotics in current clinical use. The pharmaceutical industry has largely abandoned these compounds in favor of large libraries of synthetic molecules because of difficulties in identifying new natural product antibiotics scaffolds. Advances in next-generation genome sequencing, bioinformatics, and analytical chemistry are combining to overcome barriers to natural products. Coupled with new strategies in antibiotic discovery, including inhibition of resistance, novel drug combinations, and new targets, natural products are poised for a renaissance to address what is a pressing health care crisis.

scholarly journals Suppression of Emergence of Resistance in Pathogenic Bacteria: Keeping Our Powder Dry, Part 2

2015 ◽  
Vol 60 (3) ◽  
pp. 1194-1201 ◽  
Author(s):  
G. L. Drusano ◽  
William Hope ◽  
Alasdair MacGowan ◽  
Arnold Louie
Keyword(s):  
Pathogenic Bacteria ◽  
Bacterial Resistance ◽  
Multidrug Resistant ◽  
New Drugs ◽  
Resistant Bacteria ◽  
Regulatory Review ◽  
Content Type ◽  
Drug Resistant Bacteria ◽  
Antibiotic Drug ◽  
New Chemical Entities

We are in a crisis of bacterial resistance. For economic reasons, most pharmaceutical companies are abandoning antimicrobial discovery efforts, while, in health care itself, infection control and antibiotic stewardship programs have generally failed to prevent the spread of drug-resistant bacteria. At this point, what can be done? The first step has been taken. Governments and international bodies have declared there is a worldwide crisis in antibiotic drug resistance. As discovery efforts begin anew, what more can be done to protect newly developing agents and improve the use of new drugs to suppress resistance emergence? A neglected path has been the use of recent knowledge regarding antibiotic dosing as single agents and in combination to minimize resistance emergence, while also providing sufficient early bacterial kill. In this review, we look at the data for resistance suppression. Approaches include increasing the intensity of therapy to suppress resistant subpopulations; developing concepts of clinical breakpoints to include issues surrounding suppression of resistance; and paying attention to the duration of therapy, which is another important issue for resistance suppression. New understanding of optimizing combination therapy is of interest for difficult-to-treat pathogens likePseudomonas aeruginosa,Acinetobacterspp., and multidrug-resistant (MDR)Enterobacteriaceae. These lessons need to be applied to our old drugs as well to preserve them and to be put into national and international antibiotic resistance strategies. As importantly, from a regulatory perspective, new chemical entities should have a resistance suppression plan at the time of regulatory review. In this way, we can make the best of our current situation and improve future prospects.

scholarly journals Drug Resistance of Ocular Bacteria Considering Biofilm Mechanism

2021 ◽  
Vol 271 ◽  
pp. 03041
Author(s):  
Yutong Liu ◽  
Xuanrong Xu
Keyword(s):  
Experimental Study ◽  
Drug Resistance ◽  
Bacterial Biofilm ◽  
Resistant Bacteria ◽  
Drug Resistant ◽  
Conjugation System ◽  
Resistant Genes ◽  
Drug Resistant Bacteria ◽  
Bacterial Drug Resistance ◽  
The Relationship

In order to further analyze the relationship between the coating mechanism of microorganisms and their drug resistance, a study of ocular bacterial drug resistance considering the coating mechanism of microorganisms was proposed. Firstly, the mechanism of drug resistance was analyzed, and on this basis, the experimental study was carried out. Staphylococcus aureus DH5 with RP4 was used as the control α( R) Objective to investigate the relationship between drug-resistant bacteria and coating mechanism in the cross genus conjugation system of Pseudomonas aeruginosa PAOi and donor bacteria. The conclusion is that: under the condition that the horizontal transfer of drug-resistant genes between transgeneric bacteria in biofilm is inhibited, the frequency of drug-resistant gene conjugation and transfer gradually decreases, and the inhibition of the formation of drug-resistant bacterial biofilm will directly lead to the decrease of bacterial drug resistance.

scholarly journals Limacus flavus yellow slug: bioactive molecules in the mucus

2021 ◽  
Author(s):  
Patricia Yumi Hayashida ◽  
Pedro Ismael Silva Junior
Keyword(s):  
Antimicrobial Activity ◽  
Antimicrobial Peptides ◽  
Water Solubility ◽  
Micrococcus Luteus ◽  
Chemical Characterization ◽  
New Drugs ◽  
Bioactive Molecules ◽  
Resistant Bacteria ◽  
Drug Resistant Bacteria ◽  
Wide Range

Background: Snails and slugs were used as a treatment for many health problems therefore ancient times. Since the antimicrobial resistance became a major global thread, antimicrobial peptides have been considered as a potential source for development of new drugs, especially for drug-resistant bacteria. Nowadays reports confirm that the mucous secretions have antimicrobial, antiviral and antifungal properties. Methods: The present study has the objective to characterize and evaluate antimicrobial peptides of Limacus flavus mucus. The mucus was obtained by thermal shock and submitted to RP-HPLC. Fractions were used to perform the antimicrobial activity and hemolytic assays, electrophoresis (SDS-Page Gel) and submitted to mass spectrometry (LC-MS / MS). Identification and characterization was performed by PeaksX+ software. The physicochemical parameters were evaluated with bioinformatics tools, which predicted water solubility, iso-electric point, charge net and its primary structure. Results: Three fractions were isolated from the mucus of L. flavus and presented antifungal and antibacterial activity. The mucus showed greater inhibition for filamentous fungi (Aspergillus niger), yeast (Cryptococcus neoformans), Gram positive bacteria (Bacillus subtilis, Micrococcus luteus) and Gram negative bacteria (Enterobacter cloacae). These fractions also did not show hemolytic activity for human blood cells (erythrocytes). Fractions sequences were identified and presents Mw <3kDa, WLGH, DLQW, YLRW, respectively. Conclusion: This study revealed three antimicrobial peptides of L. flavus mucus with a wide range of antimicrobial activity and its physic-chemical characterization. Keywords: Limacus flavus, mucus, slug, antimicrobial peptide, bioactive molecules, resistance, microorganisms.

Releasable antimicrobial polymer-silk coatings for combating multidrug-resistant bacteria

2021 ◽  
Author(s):  
Erna Wulandari ◽  
Rachel Budhisatria ◽  
Alexander H. Soeriyadi ◽  
Mark Willcox ◽  
Cyrille Boyer ◽  
...  
Keyword(s):  
Controlled Release ◽  
Biofilm Formation ◽  
Multidrug Resistant ◽  
Bacterial Biofilm ◽  
Resistant Bacteria ◽  
Multidrug Resistant Bacteria ◽  
Antimicrobial Polymers ◽  
Planktonic Bacteria

Controlled release of synthetic cationic antimicrobial polymers from silk-based coating for preventing bacterial biofilm formation on the surface and for killing planktonic bacteria cells.

scholarly journals Suppression of Emergence of Resistance in Pathogenic Bacteria: Keeping Our Powder Dry, Part 1

2015 ◽  
Vol 60 (3) ◽  
pp. 1183-1193 ◽  
Author(s):  
G. L. Drusano ◽  
Arnold Louie ◽  
Alasdair MacGowan ◽  
William Hope
Keyword(s):  
Pathogenic Bacteria ◽  
Bacterial Resistance ◽  
Multidrug Resistant ◽  
New Drugs ◽  
Resistant Bacteria ◽  
Regulatory Review ◽  
Content Type ◽  
Drug Resistant Bacteria ◽  
Antibiotic Drug ◽  
New Chemical Entities

We are in a crisis of bacterial resistance. For economic reasons, most pharmaceutical companies are abandoning antimicrobial discovery efforts, while, in health care itself, infection control and antibiotic stewardship programs have generally failed to prevent the spread of drug-resistant bacteria. At this point, what can be done? The first step has been taken. Governments and international bodies have declared there is a worldwide crisis in antibiotic drug resistance. As discovery efforts begin anew, what more can be done to protect newly developing agents and improve the use of new drugs to suppress resistance emergence? A neglected path has been the use of recent knowledge regarding antibiotic dosing as single agents and in combination to minimize resistance emergence, while also providing sufficient early bacterial kill. In this review, we look at the data for resistance suppression. Approaches include increasing the intensity of therapy to suppress resistant subpopulations; developing concepts of clinical breakpoints to include issues surrounding suppression of resistance; and paying attention to the duration of therapy, which is another important issue for resistance suppression. New understanding of optimizing combination therapy is of interest for difficult-to-treat pathogens likePseudomonas aeruginosa,Acinetobacterspp., and multidrug-resistant (MDR)Enterobacteriaceae. These lessons need to be applied to our old drugs to preserve them as well and need to be put into national and international antibiotic resistance strategies. As importantly, from a regulatory perspective, new chemical entities should have a corresponding resistance suppression plan at the time of regulatory review. In this way, we can make the best of our current situation and improve future prospects.

scholarly journals Staphylococcal Phage in Combination with Staphylococcus epidermidis as a Potential Treatment for Staphylococcus aureus-Associated Atopic Dermatitis and Suppressor of Phage-Resistant Mutants

Viruses ◽  
2020 ◽  
Vol 13 (1) ◽  
pp. 7
Author(s):  
Yuzuki Shimamori ◽  
Shoichi Mitsunaka ◽  
Hirotaka Yamashita ◽  
Tohru Suzuki ◽  
Tomoe Kitao ◽  
...  
Keyword(s):  
Staphylococcus Aureus ◽  
Atopic Dermatitis ◽  
Staphylococcus Epidermidis ◽  
Phage Therapy ◽  
Opportunistic Pathogen ◽  
Resistant Bacteria ◽  
Skin Infections ◽  
Disease Exacerbation ◽  
Drug Resistant Bacteria ◽  
Resistant Mutants

Atopic dermatitis is accompanied by the abnormal overgrowth of Staphylococcus aureus, a common cause of skin infections and an opportunistic pathogen. Although administration of antibiotics is effective against S. aureus, the resulting reduction in healthy microbiota and the emergence of drug-resistant bacteria are of concern. We propose that phage therapy can be an effective strategy to treat atopic dermatitis without perturbing the microbiota structure. In this study, we examined whether the S. aureus phage SaGU1 could be a tool to counteract the atopic exacerbation induced by S. aureus using an atopic mouse model. Administration of SaGU1 to the back skin of mice reduced both S. aureus counts and the disease exacerbation caused by S. aureus. Furthermore, the S. aureus-mediated exacerbation of atopic dermatitis with respect to IgE plasma concentration and histopathological findings was ameliorated by the application of SaGU1. We also found that Staphylococcus epidermidis, a typical epidermal symbiont in healthy skin, significantly attenuated the emergence of SaGU1-resistant S. aureus under co-culture with S. aureus and S. epidermidis in liquid culture infection experiments. Our results suggest that phage therapy using SaGU1 could be a promising clinical treatment for atopic dermatitis.

Opportunities for natural products in 21st century antibiotic discovery

2017 ◽  
Vol 34 (7) ◽  
pp. 694-701 ◽  
Author(s):  
Gerard D. Wright
Keyword(s):  
Natural Products ◽  
Natural Product ◽  
21St Century ◽  
New Drugs ◽  
Natural Product Research ◽  
Antibiotic Discovery

Natural product research is poised to regain prominence in delivering new drugs to solve the antibiotic crisis.

scholarly journals A comprehensive review of the botany, ethnopharmacology, biochemistry, pharmacology, pharmacokinetics and toxicity of Filifolium sibiricum (L.)Kitam

2021 ◽  
Vol 16 (1) ◽  
Author(s):  
Shaowa Lv ◽  
Qian Qiu ◽  
Qiuhong Wang ◽  
Haixue Kuang
Keyword(s):  
Folk Medicine ◽  
New Drugs ◽  
Research Progress ◽  
Resistant Bacteria ◽  
Pharmacological Activities ◽  
Traditional Chinese Herbal Medicine ◽  
Scientific Databases ◽  
Drug Resistant Bacteria ◽  
Pharmacological Studies ◽  
Analgesic Activities

AbstractFilifoliumsibiricum (L.)Kitam (F.sibiricum), a compositae plant, is especially used to inhibit drug-resistant bacteria in folk medicine. Modern pharmacological studies also confirmed a variety of pharmacological properties about sedative activities, antibacterial activity, anti-inflammatory activity, analgesic activities, antitussive and asthma relieving. In this paper, the research progress of F.sibiricum in botany, ethnopharmacology, phytochemistry, pharmacology, pharmacokinetics and toxicology was reviewed. Prospects for future investigation and application of this herb were also discussed. Information on F.sibiricum was gathered from various sources, including books on traditional Chinese herbal medicine and scientific databases such as PubMed, Google Scholar, Science Direct, Baidu Scholar, CNKI and other professional websites. The results indicate that ~ 66 chemical compounds were isolated and identified from F.sibiricum. Among them, flavonoids are generally considered to be the main bioactive and characteristic ingredients. F.sibiricum is a traditional Chinese medicine with pharmacological activities such as the immune system, nervous system, respiratory system and cardiovascular and cerebrovascular systems. Most importantly, we should concentrate on developing new drugs related to F.sibiricum, so as to exert greater potential for treatment.

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