scholarly journals Mining and Biosynthesis of Bioactive Lanthipeptides From Microorganisms

2021 ◽  
Vol 9 ◽  
Author(s):  
Caiyun Li ◽  
Khorshed Alam ◽  
Yiming Zhao ◽  
Jinfang Hao ◽  
Qing Yang ◽  
...  
Keyword(s):  
New Technologies ◽  
Genome Mining ◽  
Multidrug Resistant ◽  
Health Issues ◽  
Antimicrobial Drugs ◽  
Drug Candidates ◽  
Chemical Structures ◽  
Modified Peptides ◽  
Biosynthetic Engineering ◽  
High Diversity

Antimicrobial resistance is one of the most serious public health issues in the worldwide and only a few new antimicrobial drugs have been discovered in recent decades. To overcome the ever-increasing emergence of multidrug-resistant (MDR) pathogens, discovery of new natural products (NPs) against MDR pathogens with new technologies is in great demands. Lanthipeptides which are ribosomally synthesized and post-translationally modified peptides (RiPPs) display high diversity in their chemical structures and mechanisms of action. Genome mining and biosynthetic engineering have also yielded new lanthipeptides, which are a valuable source of drug candidates. In this review we cover the recent advances in the field of microbial derived lanthipeptide discovery and development.

scholarly journals A Deep Learning Genome-Mining Strategy Improves Biosynthetic Gene Cluster Prediction

2018 ◽  
Author(s):  
Geoffrey D. Hannigan ◽  
David Prihoda ◽  
Andrej Palicka ◽  
Jindrich Soukup ◽  
Ondrej Klempir ◽  
...  
Keyword(s):  
Natural Products ◽  
Deep Learning ◽  
Learning Strategy ◽  
Genome Mining ◽  
Gene Clusters ◽  
Biosynthetic Gene Cluster ◽  
Biosynthetic Gene ◽  
Antimicrobial Drugs ◽  
Drug Candidates ◽  
Significant Step

AbstractNatural products represent a rich reservoir of small molecule drug candidates utilized as antimicrobial drugs, anticancer therapies, and immunomodulatory agents. These molecules are microbial secondary metabolites synthesized by co-localized genes termed Biosynthetic Gene Clusters (BGCs). The increase in full microbial genomes and similar resources has led to development of BGC prediction algorithms, although their precision and ability to identify novel BGC classes could be improved. Here we present a deep learning strategy (DeepBGC) that offers more accurate BGC identification and an improved ability to extrapolate and identify novel BGC classes compared to existing tools. We supplemented this with downstream random forest classifiers that accurately predicted BGC product classes and potential chemical activity. Application of DeepBGC to bacterial genomes uncovered previously undetectable BGCs that may code for natural products with novel biologic activities. The improved accuracy and classification ability of DeepBGC represents a significant step forward forin-silicoBGC identification.

scholarly journals A deep learning genome-mining strategy for biosynthetic gene cluster prediction

2019 ◽  
Vol 47 (18) ◽  
pp. e110-e110 ◽  
Author(s):  
Geoffrey D Hannigan ◽  
David Prihoda ◽  
Andrej Palicka ◽  
Jindrich Soukup ◽  
Ondrej Klempir ◽  
...  
Keyword(s):  
Natural Products ◽  
Deep Learning ◽  
Learning Strategy ◽  
Genome Mining ◽  
Gene Clusters ◽  
Biosynthetic Gene Cluster ◽  
Learning Tools ◽  
Biosynthetic Gene ◽  
Antimicrobial Drugs ◽  
Drug Candidates

Abstract Natural products represent a rich reservoir of small molecule drug candidates utilized as antimicrobial drugs, anticancer therapies, and immunomodulatory agents. These molecules are microbial secondary metabolites synthesized by co-localized genes termed Biosynthetic Gene Clusters (BGCs). The increase in full microbial genomes and similar resources has led to development of BGC prediction algorithms, although their precision and ability to identify novel BGC classes could be improved. Here we present a deep learning strategy (DeepBGC) that offers reduced false positive rates in BGC identification and an improved ability to extrapolate and identify novel BGC classes compared to existing machine-learning tools. We supplemented this with random forest classifiers that accurately predicted BGC product classes and potential chemical activity. Application of DeepBGC to bacterial genomes uncovered previously undetectable putative BGCs that may code for natural products with novel biologic activities. The improved accuracy and classification ability of DeepBGC represents a major addition to in-silico BGC identification.

scholarly journals Is It Possible to Create Antimicrobial Peptides Based on the Amyloidogenic Sequence of Ribosomal S1 Protein of P. aeruginosa?

2021 ◽  
Vol 22 (18) ◽  
pp. 9776
Author(s):  
Sergei Y. Grishin ◽  
Pavel A. Domnin ◽  
Sergey V. Kravchenko ◽  
Viacheslav N. Azev ◽  
Leila G. Mustaeva ◽  
...  
Keyword(s):  
Antimicrobial Peptides ◽  
Antimicrobial Properties ◽  
Multidrug Resistant ◽  
Amyloid Formation ◽  
Gram Negative Bacteria ◽  
Antimicrobial Drugs ◽  
Hybrid Peptides ◽  
Modified Peptides ◽  
Amyloidogenic Region ◽  
Two Hybrid

The development and testing of new antimicrobial peptides (AMPs) represent an important milestone toward the development of new antimicrobial drugs that can inhibit the growth of pathogens and multidrug-resistant microorganisms such as Pseudomonas aeruginosa, Gram-negative bacteria. Most AMPs achieve these goals through mechanisms that disrupt the normal permeability of the cell membrane, which ultimately leads to the death of the pathogenic cell. Here, we developed a unique combination of a membrane penetrating peptide and peptides prone to amyloidogenesis to create hybrid peptide: “cell penetrating peptide + linker + amyloidogenic peptide”. We evaluated the antimicrobial effects of two peptides that were developed from sequences with different propensities for amyloid formation. Among the two hybrid peptides, one was found with antibacterial activity comparable to antibiotic gentamicin sulfate. Our peptides showed no toxicity to eukaryotic cells. In addition, we evaluated the effect on the antimicrobial properties of amino acid substitutions in the non-amyloidogenic region of peptides. We compared the results with data on the predicted secondary structure, hydrophobicity, and antimicrobial properties of the original and modified peptides. In conclusion, our study demonstrates the promise of hybrid peptides based on amyloidogenic regions of the ribosomal S1 protein for the development of new antimicrobial drugs against P. aeruginosa.

Flavonoids as P-gp Inhibitors: A Systematic Review of SARs

2019 ◽  
Vol 26 (25) ◽  
pp. 4799-4831 ◽  
Author(s):  
Jiahua Cui ◽  
Xiaoyang Liu ◽  
Larry M.C. Chow
Keyword(s):  
Molecular Mechanisms ◽  
Metastatic Cancer ◽  
Drug Candidates ◽  
Chemical Structures ◽  
Transporter Family ◽  
Promising Area ◽  
New Generation ◽  
Nontoxic Inhibitors

P-glycoprotein, also known as ABCB1 in the ABC transporter family, confers the simultaneous resistance of metastatic cancer cells towards various anticancer drugs with different targets and diverse chemical structures. The exploration of safe and specific inhibitors of this pump has always been the pursuit of scientists for the past four decades. Naturally occurring flavonoids as benzopyrone derivatives were recognized as a class of nontoxic inhibitors of P-gp. The recent advent of synthetic flavonoid dimer FD18, as a potent P-gp modulator in reversing multidrug resistance both in vitro and in vivo, specifically targeted the pseudodimeric structure of the drug transporter and represented a new generation of inhibitors with high transporter binding affinity and low toxicity. This review concerned the recent updates on the structure-activity relationships of flavonoids as P-gp inhibitors, the molecular mechanisms of their action and their ability to overcome P-gp-mediated MDR in preclinical studies. It had crucial implications on the discovery of new drug candidates that modulated the efflux of ABC transporters and also provided some clues for the future development in this promising area.

Epidemiology of Technology Use and Mental Health in the United States

2020 ◽  
pp. 41-56
Author(s):  
Seth W. Whiting ◽  
Rani A. Hoff
Keyword(s):  
Mental Health ◽  
United States ◽  
Technology Use ◽  
New Technologies ◽  
Role Playing ◽  
The United States ◽  
Mass Scale ◽  
Online Gambling ◽  
Health Issues ◽  
Mental Health Issues

Advancements in technologies and their mass-scale adoption throughout the United States create rapid changes in how people interact with the environment and each other and how they live and work. As technologies become commonplace in society through increased availability and affordability, several problems may emerge, including disparate use among groups, which creates divides in attainment of the beneficial aspects of a technology’s use and coinciding mental health issues. This chapter briefly overviews new technologies and associated emerging applications in information communication technologies, social media networks, video games and massively multiplayer online role-playing games, and online gambling, then examines the prevalence of use among the general population and its subgroups and further discusses potential links between mental health issues associated with each technology and implications of overuse.

scholarly journals Multidrug Resistence Prevalence in COVID Area

Life ◽  
2021 ◽  
Vol 11 (7) ◽  
pp. 601
Author(s):  
Caterina Aurilio ◽  
Pasquale Sansone ◽  
Antonella Paladini ◽  
Manlio Barbarisi ◽  
Francesco Coppolino ◽  
...  
Keyword(s):  
Bacterial Resistance ◽  
Respiratory Infections ◽  
Prolonged Mechanical Ventilation ◽  
Viral Disease ◽  
Multidrug Resistant ◽  
Resistant Bacteria ◽  
Antimicrobial Drugs ◽  
Infected People ◽  
Therapeutic Procedures ◽  
Viral Respiratory Infections

Coronavirus disease 2019 (COVID-19), caused by SARS-CoV-2, is often complicated by severe acute respiratory syndrome. The new coronavirus outbreak started in China in December 2019 and rapidly spread around the world. The high diffusibility of the virus was the reason for the outbreak of the pandemic viral disease, reaching more than 100 million infected people globally by the first three months of 2021. In the various treatments used up to now, the use of antimicrobial drugs for the management, especially of bacterial co-infections, is very frequent in patients admitted to intensive care. In addition, critically ill patients with SARS-CoV-2 infection are subjected to prolonged mechanical ventilation and other therapeutic procedures often responsible for developing hospital co-infections due to multidrug-resistant bacteria. Co-infections contribute to the increase in the morbidity–mortality of viral respiratory infections. We performed this study to review the recent articles published on the antibiotic bacterial resistance and viruses to predict risk factors of coronavirus disease 2019 and to assess the multidrug resistance in patients hospitalized in the COVID-19 area.

scholarly journals Liposomes as Antibiotic Delivery Systems: A Promising Nanotechnological Strategy against Antimicrobial Resistance

Molecules ◽  
2021 ◽  
Vol 26 (7) ◽  
pp. 2047
Author(s):  
Magda Ferreira ◽  
Maria Ogren ◽  
Joana N. R. Dias ◽  
Marta Silva ◽  
Solange Gil ◽  
...  
Keyword(s):  
Antimicrobial Resistance ◽  
Bacterial Infections ◽  
Private Investment ◽  
Therapeutic Index ◽  
Multidrug Resistant ◽  
Current Treatment ◽  
Delivery Systems ◽  
Resistant Bacteria ◽  
Bacterial Cells ◽  
Antimicrobial Drugs

Antimicrobial drugs are key tools to prevent and treat bacterial infections. Despite the early success of antibiotics, the current treatment of bacterial infections faces serious challenges due to the emergence and spread of resistant bacteria. Moreover, the decline of research and private investment in new antibiotics further aggravates this antibiotic crisis era. Overcoming the complexity of antimicrobial resistance must go beyond the search of new classes of antibiotics and include the development of alternative solutions. The evolution of nanomedicine has allowed the design of new drug delivery systems with improved therapeutic index for the incorporated compounds. One of the most promising strategies is their association to lipid-based delivery (nano)systems. A drug’s encapsulation in liposomes has been demonstrated to increase its accumulation at the infection site, minimizing drug toxicity and protecting the antibiotic from peripheral degradation. In addition, liposomes may be designed to fuse with bacterial cells, holding the potential to overcome antimicrobial resistance and biofilm formation and constituting a promising solution for the treatment of potential fatal multidrug-resistant bacterial infections, such as methicillin resistant Staphylococcus aureus. In this review, we aim to address the applicability of antibiotic encapsulated liposomes as an effective therapeutic strategy for bacterial infections.

scholarly journals A molecular architectural design that promises potent antimicrobial activity against multidrug-resistant pathogens

2021 ◽  
Vol 13 (1) ◽  
Author(s):  
Bing Yuan ◽  
Jiaojiao Liu ◽  
Zhixiong Deng ◽  
Lin Wei ◽  
Wenwen Li ◽  
...  
Keyword(s):  
Architectural Design ◽  
Building Blocks ◽  
Multidrug Resistant ◽  
In Vitro Cytotoxicity ◽  
Antimicrobial Drugs ◽  
Minimal Inhibitory Concentrations ◽  
Antimicrobial Efficiency ◽  
Multidrug Resistant Pathogens

AbstractAddressing the devastating threat of drug-resistant pathogens requires the discovery of new antibiotics with advanced action mechanisms and/or novel strategies for drug design. Herein, from a biophysical perspective, we design a class of synthetic antibacterial complexes with specialized architectures based on melittin (Mel), a natural antimicrobial peptide, and poly(ethylene glycol) (PEG), a clinically available agent, as building blocks that show potent and architecture-modulated antibacterial activity. Among the complexes, the flexibly linear complex consisting of one Mel terminally connected with a long-chained PEG (e.g., PEG12k–1*Mel) shows the most pronounced improvement in performance compared with pristine Mel, with up to 500% improvement in antimicrobial efficiency, excellent in vitro activity against multidrug-resistant pathogens (over a range of minimal inhibitory concentrations of 2–32 µg mL−1), a 68% decrease in in vitro cytotoxicity, and a 57% decrease in in vivo acute toxicity. A lipid-specific mode of action in membrane recognition and an accelerated “channel” effect in perforating the bacterial membrane of the complex are described. Our results introduce a new way to design highly efficient and low-toxicity antimicrobial drugs based on architectural modulations with clinically available agents.

scholarly journals Corrigendum to “high diversity of virulent and multidrug resistant Stenotrophomonas maltophilia in Iraq” gene reports, volume 23 (2021)

Gene Reports ◽  
2021 ◽  
pp. 101264
Author(s):  
Raed Obaid Saleh ◽  
Bashdar Mahmud Hussen ◽  
Shaden M.H. Mubarak ◽  
Seyyed Khalil Shokouhi Mostafavi
Keyword(s):  
Stenotrophomonas Maltophilia ◽  
Multidrug Resistant ◽  
High Diversity
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