scholarly journals Synergizing the potential of bacterial genomics and metabolomics to find novel antibiotics

2021 ◽  
Author(s):  
Fabian Panter ◽  
Chantal D. Bader ◽  
Rolf Müller
Keyword(s):  
Natural Products ◽  
Antimicrobial Resistance ◽  
Public Concern ◽  
Bacterial Genomics ◽  
Technological Developments ◽  
Novel Antibiotics

Antimicrobial resistance is a major public concern and novel antibiotics are largely based on natural products. We summarize recent analytical and genome based technological developments that gain increasing importance in the natural products field.

scholarly journals From bugs to drugs: Combating antimicrobial resistance by discovering novel antibiotics

2018 ◽  
Vol 12 (02.1) ◽  
pp. 3S
Author(s):  
Antoine Abou Fayad ◽  
Dana Itani ◽  
Mariam Miari ◽  
Arax Tanelian ◽  
Sereen Iweir ◽  
...  
Keyword(s):  
Escherichia Coli ◽  
Antibacterial Activity ◽  
Natural Products ◽  
Antimicrobial Resistance ◽  
Soil Microorganisms ◽  
Soil Samples ◽  
16S Rrna Analysis ◽  
Strain Isolation ◽  
Bacillus Subtilis Atcc ◽  
Novel Antibiotics

Introduction: Antimicrobial resistance (AMR) is emerging at an alarming rate as mortality due to resistant pathogens could rise to 10 million per year by 2050. Since AMR is against all clinically utilized antibiotics, finding novel antimicrobials with unexploited targets remains the main goal worldwide.  Soil microorganisms produce natural products as a significant number of drugs in clinical use are derived from these metabolites. Actinomycetes and Myxobacteria are soil dwelling microorganisms that produce secondary metabolites to be screened for antibacterial activity. More than 80% of clinically utilized antibiotics are either natural products or natural product-derived molecules such as vancomycin, teicoplanin, daptomycin, and tetracycline. This study aims to isolate and identify novel antimicrobials from Actinomycetes and Myxobacteria. Methodology: Soil samples were collected from several areas in Lebanon. Samples were serially diluted for Actinomycetes isolation and boiled for Myxobacteria extraction, then plated on suitable media. Colonies obtained were purified and subjected to genomic DNA extraction then 16s rRNA analysis. Novel isolates were tested for their antimicrobial activity against Gram-positive Bacillus subtilis (ATCC 6051), Staphylococcus aureus (ATCC 29213, Newman, N315), Enterococcus faecalis (ATCC 19433), and Enterococcus faecium (DSMZ 17050), and Gram-negative Escherichia coli (ATCC 9637), Klebsiella pneumoniae (DSMZ), Pseudomonas aeruginosa (ATCC 27853, MEXAB), and Acinetobacter baumannii (ATCC 15308). Results: Strain isolation and cultivation yielded a number of novel isolates whose extracts demonstrated strong antibacterial activity against pathogens including MRSA, VRE, and Escherichia coli (ATCC 9637). Conclusion: Our efforts now focus on purifying these compounds, elucidate their structures and study their mode of action.

The Emergence of Antimicrobial Resistance as a Public Matter of Concern: A Swedish History of a “Transformative Event”

2018 ◽  
Vol 31 (4) ◽  
pp. 477-500 ◽  
Author(s):  
Hedvig Gröndal
Keyword(s):  
Antimicrobial Resistance ◽  
Disease Control ◽  
Crucial Role ◽  
Professional Organization ◽  
Public Concern ◽  
History Of ◽  
Swedish History

ArgumentThis article examines how antimicrobial resistance (AMR) came to be constituted as a matter of public concern in Sweden in conjunction with the development of an inter-professional organization called Strama, founded to promote rational prescription of antibiotics. An outbreak of penicillin-resistant pneumococci in the mid-1990s was crucial for this development, because it brought attention to AMR as an urgent public threat. This outbreak fuelled the constitution of AMR as caused by consumption of antibiotics and as a matter of disease control. As a consequence, Strama was able to mobilize the Swedish health officers responsible for disease control. The outbreak is conceptualized as a “transformative event” – an event that makes an issue and its associated risks concrete and urgent. Transformative events play the crucial role of expediting the transformation of issues into matters of public concern.

scholarly journals Metabolomics in the natural products field – a gateway to novel antibiotics

2015 ◽  
Vol 13 ◽  
pp. 11-17 ◽  
Author(s):  
Changsheng Wu ◽  
Hye Kyong Kim ◽  
Gilles P. van Wezel ◽  
Young Hae Choi
Keyword(s):  
Natural Products ◽  
Novel Antibiotics

scholarly journals Targeting Bacterial Gyrase with Cystobactamid, Fluoroquinolone, and Aminocoumarin Antibiotics Induces Distinct Molecular Signatures in Pseudomonas aeruginosa

mSystems ◽  
2021 ◽  
Author(s):  
Raimo Franke ◽  
Heike Overwin ◽  
Susanne Häussler ◽  
Mark Brönstrup
Keyword(s):  
Pseudomonas Aeruginosa ◽  
Cell Wall ◽  
Protein Synthesis ◽  
Dna Replication ◽  
Antimicrobial Resistance ◽  
Bacterial Pathogens ◽  
Molecular Signatures ◽  
Successful Therapy ◽  
Cell Wall Synthesis ◽  
Novel Antibiotics

Novel antibiotics are urgently needed to tackle the growing worldwide problem of antimicrobial resistance. Bacterial pathogens possess few privileged targets for a successful therapy: the majority of existing antibiotics as well as current candidates in development target the complex bacterial machinery for cell wall synthesis, protein synthesis, or DNA replication.

scholarly journals Antimicrobial Resistance and Sensitivity of Phytophthora agathidicida

2021 ◽  
Author(s):  
Kaitlyn Daley
Keyword(s):  
Natural Products ◽  
New Zealand ◽  
Antimicrobial Resistance ◽  
Plant Pathogens ◽  
Keystone Species ◽  
Resistance Mutations ◽  
E Coli ◽  
Oxysterol Binding Protein ◽  
Significant Difference

Members of the oomycete genus Phytophthora are highly infectious plant pathogens. P. agathidicida affects the New Zealand native keystone species Agathis australis(kauri) and is the cause of kauri dieback. The complex oomycete lifecycle makes Phytophthora infections hard to manage. The current management of kauri dieback has been limited and antimicrobial resistance is a concern. Phosphite agrichemical preparations are commonly used in the control of Phytophthora diseases, including kauri dieback. However, phosphite is not the only option; the agrichemicals oxathiapiprolin, and the plant-derived natural products polygodial and falcarindiol, have also been shown to have activity against P. agathidicida. The overall goal of this thesis was to further explore aspects of sensitivity and resistance of P. agathidicidatowards these four compounds.In New Zealand, there are three commercially available phosphite preparations, Agri-Fos 600, Phosgard, and Foschek. All previous studies have used Agri-Fos 600, so the first aim was to determine whether the particular formulation altered anti-oomycete activity. No significant difference was found between the 50% inhibitory concentrations (EC50 values) for the three formulations. Interestingly, however, formulating polygodial and falcarindiol with the surfactants and other non-phosphite ingredients of Foschek led to a significant increase in their inhibitory effects. The second aim of this thesis was to implement a serial passaging protocol for P. agathidicida and attempt to isolate mutants with increased resistance to phosphite, polygodial or falcarindiol. Serial passaging was carried out on amended agar plated with increasing concentrations of each chemical. However, even after 7 passages, over 16-18 weeks of growth, no mutants with increased resistance were isolated. This could be due to the complicated modes of action of the polygodial, falcarindioland phosphite, which makes it likely that several specific mutations are required to effect resistance. <br>IIOxathiapiprolin is a highly potent, new anti-oomycete agrichemical. It targets the Phytophthora oxysterol binding protein (OSBP) related protein (ORP1). Mutations in this protein are known to give oxathiapiprolin resistance in other species of Phytophthora; however, the P. agathidicida protein (PaORP1) has never been studied. In this work, the gene for PaORP1 was partially sequenced from five P. agathidicida isolates. None contained any of the known resistance mutations. A new protocol for expressing PaORP1 in E. coli and purifying it using immobilised metal affinity chromatography was also developed. After optimisation, this protocol yielded up to 30 mg of purified protein per litre of E. coli culture and is the first successful example of heterologously expressing and purifying any P. agathidicida protein. In future, this will allow the biomolecular interaction between PaORP1 and oxathiapiprolin to be studied in more detail. Overall, the work presented in this thesis assessed commercial formulations of phosphite, established a directed evolution protocol for studying resistance in P. agathidicida, and reported the first in vitro characterisation of a P. agathidicidaprotein. This research suggests that commercial formulation of plant-derived natural products may be a powerful new approach for combatting kauri dieback and, promisingly, also suggests that the risk of developing resistance to these compounds might be low.

scholarly journals Bioprospecting for antituberculosis natural products – A review

2021 ◽  
Vol 19 (1) ◽  
pp. 1074-1088
Author(s):  
Olabisi Flora Davies-Bolorunduro ◽  
Abraham Ajayi ◽  
Isaac Adeyemi Adeleye ◽  
Alfinda Novi Kristanti ◽  
Nanik Siti Aminah
Keyword(s):  
Natural Products ◽  
Mycobacterium Tuberculosis ◽  
High Throughput Screening ◽  
Antitubercular Drug ◽  
Natural Sources ◽  
Resource Limited ◽  
Novel Drugs ◽  
Mdr Tb ◽  
Drug Leads ◽  
Novel Antibiotics

Abstract There has been an increase in the reported cases of tuberculosis, a disease caused by Mycobacterium tuberculosis, which is still currently affecting most of the world’s population, especially in resource-limited countries. The search for novel antitubercular chemotherapeutics from underexplored natural sources is therefore of paramount importance. The renewed interest in studies related to natural products, driven partly by the growing incidence of MDR-TB, has increased the prospects of discovering new antitubercular drug leads. This is because most of the currently available chemotherapeutics such as rifampicin and capreomycin used in the treatment of TB were derived from natural products, which are proven to be an abundant source of novel drugs used to treat many diseases. To meet the global need for novel antibiotics from natural sources, various strategies for high-throughput screening have been designed and implemented. This review highlights the current antitubercular drug discovery strategies from natural sources.

Enzyme alchemy: cell-free synthetic biochemistry for natural products

2019 ◽  
Vol 3 (5) ◽  
pp. 529-535 ◽  
Author(s):  
Simon J. Moore
Keyword(s):  
Natural Products ◽  
Total Synthesis ◽  
Natural Product ◽  
Living Cell ◽  
Chemical Biology ◽  
Low Cost ◽  
Challenges And Opportunities ◽  
Whole Cell Biotransformation ◽  
Synthesis Routes ◽  
Novel Antibiotics

Cell-free synthetic biochemistry aims to engineer chemical biology by exploiting biosynthetic dexterity outside of the constraints of a living cell. One particular use is for making natural products, where cell-free systems have initially demonstrated feasibility in the biosynthesis of a range of complex natural products classes. This has shown key advantages over total synthesis, such as increased yield, enhanced regioselectivity, use of reduced temperatures and less reaction steps. Uniquely, cell-free synthetic biochemistry represents a new area that seeks to advance upon these efforts and is particularly useful for defining novel synthetic pathways to replace natural routes and optimising the production of complex natural product targets from low-cost precursors. Key challenges and opportunities will include finding solutions to scaled-up cell-free biosynthesis, as well as the targeting of high value and toxic natural products that remain challenging to make either through whole-cell biotransformation platforms or total synthesis routes. Although underexplored, cell-free synthetic biochemistry could also be used to develop ‘non-natural’ natural products or so-called xenobiotics for novel antibiotics and drugs, which can be difficult to engineer directly within a living cell.

scholarly journals A Comprehensive Review on Medicinal Plants as Antimicrobial Therapeutics: Potential Avenues of Biocompatible Drug Discovery

Metabolites ◽  
2019 ◽  
Vol 9 (11) ◽  
pp. 258 ◽  
Author(s):  
Uttpal Anand ◽  
Nadia Jacobo-Herrera ◽  
Ammar Altemimi ◽  
Naoufal Lakhssassi
Keyword(s):  
Multidrug Resistance ◽  
Drug Discovery ◽  
Antimicrobial Resistance ◽  
Medicinal Plants ◽  
Secondary Metabolites ◽  
Comprehensive Review ◽  
Rich Diversity ◽  
Potential Benefits ◽  
Wonder Drug ◽  
Novel Antibiotics

The war on multidrug resistance (MDR) has resulted in the greatest loss to the world’s economy. Antibiotics, the bedrock, and wonder drug of the 20th century have played a central role in treating infectious diseases. However, the inappropriate, irregular, and irrational uses of antibiotics have resulted in the emergence of antimicrobial resistance. This has resulted in an increased interest in medicinal plants since 30–50% of current pharmaceuticals and nutraceuticals are plant-derived. The question we address in this review is whether plants, which produce a rich diversity of secondary metabolites, may provide novel antibiotics to tackle MDR microbes and novel chemosensitizers to reclaim currently used antibiotics that have been rendered ineffective by the MDR microbes. Plants synthesize secondary metabolites and phytochemicals and have great potential to act as therapeutics. The main focus of this mini-review is to highlight the potential benefits of plant derived multiple compounds and the importance of phytochemicals for the development of biocompatible therapeutics. In addition, this review focuses on the diverse effects and efficacy of herbal compounds in controlling the development of MDR in microbes and hopes to inspire research into unexplored plants with a view to identify novel antibiotics for global health benefits.

Sign in / Sign up

Export Citation Format

Share Document