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Antibiotics
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Discovery of Novel Antibiotics
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Discovery of Novel Antibiotics

A special issue of Antibiotics (ISSN 2079-6382). This special issue belongs to the section "Novel Antimicrobial Agents".

Deadline for manuscript submissions: closed (30 April 2021) | Viewed by 17898

Special Issue Editors

Dr. Calado Cecília R.C.

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Guest Editor
ISEL-Instituto Superior de Engenharia de Lisboa, Instituto Politécnico de Lisboa, R. Conselheiro Emídio Navarro, 1549-014 Lisboa, Portugal
Interests: drugs discovery; biomarkers discovery; medical diagnosis; biopharmaceutical engineering
Special Issues, Collections and Topics in MDPI journals
Prof. Luis Pina Fonseca

E-Mail Website
Guest Editor
Institute of Bioengineering and Biosciences (iBB), Instituto Superior Técnico (IST), Universidade de Lisboa (UL), Av. Rovisco Pais, 1049-001 Lisboa, Portugal
Interests: biocatalysis; biosensors; biomedical devices; bioencapsulation; drug delivery; industrial biotechnology

Special Issue Information

Dear Colleagues,

The discovery of antibiotics revolutionised medicine. However, due to the spread of antibiotic resistance—resulting in the increasing prevalence of multi-drug resistant bacteria, and a decrease in the number of new antibiotics introduced for clinical usage—both the development of novel antibiotics and seeking new and innovative strategies have become crucial. The urgent need for new antibiotics is especially relevant for multidrug-resistant tuberculosis, Gram-negative bacteria and community-acquired infections.

This Special Issue aims to promote a forum to discuss current challenges and solutions in the development of novel antibiotics. To leverage fast breakthroughs in such a complex domain, a high diversity of strategies must be considered; for example, strategies based on medicinal chemistry, including semi-synthetic and synthetic products, target-based drug discovery, combinatorial biosynthesis, the screening of natural compounds, new screening methods, novel cultivation methods for previously “unculturable” bacteria, and phage therapy among other approaches.

Prof. Luis Pina Fonseca
Dr. Calado Cecília R.C.
Guest Editors

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Antibiotics is an international peer-reviewed open access monthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2900 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • antibiotics Discovery
  • drugs Screening
  • antibiotics resistance
  • antimicrobial resistance
  • systems biology
  • gene variant

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Related Special Issue

Published Papers (4 papers)

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Research

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15 pages, 2841 KiB  
Article
Potential of FTIR-Spectroscopy for Drugs Screening against Helicobacter pylori
by Pedro S. Sampaio and Cecília R. C. Calado
Antibiotics 2020, 9(12), 897; https://doi.org/10.3390/antibiotics9120897 - 12 Dec 2020
Cited by 10 | Viewed by 3437
Abstract
Helicobacter pylori colonizes the human stomach of half of the world’s population. The infection if not treated, persists through life, leading to chronic gastric inflammation, that may progress to severe diseases as peptic ulcer, gastric adenocarcinoma, and mucosa-associated lymphoid tissue lymphoma. The first [...] Read more.
Helicobacter pylori colonizes the human stomach of half of the world’s population. The infection if not treated, persists through life, leading to chronic gastric inflammation, that may progress to severe diseases as peptic ulcer, gastric adenocarcinoma, and mucosa-associated lymphoid tissue lymphoma. The first line of treatment, based on 7 to 21 days of two antibiotics associated with a proton pump inhibitor, is, however, already failing most due to patient non-compliance that leads to antibiotic resistance. It is, therefore, urgent to screen for new and more efficient antimicrobials against this bacterium. In this work, Fourier Transform Infrared (FTIR) spectroscopy was evaluated to screen new drugs against H. pylori, in rapid (between 1 to 6 h), and high-throughput mode and based on a microliter volume processes in relation to the agar dilution method. The reference H. pylori strains 26,695 and J99, were evaluated against a peptide-based antimicrobial and the clinical antibiotic clarithromycin, respectively. After optimization of the assay conditions, as the composition of the incubation mixture, the time of incubation, and spectral pre-processing, it was possible to reproducibly observe the effect of the drug on the bacterial molecular fingerprint as pointed by the spectra principal component analysis. The spectra, obtained from both reference strains, after its incubation with drugs concentrations lower than the MIC, presented peak ratios statistically different (p < 0.05) in relation to the bacteria incubated with drugs concentrations equal or higher to the MIC. It was possible to develop a partial least square regression model, enabling to predict from spectra of both bacteria strains, the drug concentration on the assay, with a high correlation coefficient between predicted and experimental data (0.91) and root square error of 40% of the minimum inhibitory concentration. All this points to the high potential of the technique for drug screening against this fastidious growth bacterium. Full article
(This article belongs to the Special Issue Discovery of Novel Antibiotics)
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16 pages, 1234 KiB  
Article
Mycobacterium vaccae Adaptation to Disinfectants and Hand Sanitisers, and Evaluation of Cross-Tolerance with Antimicrobials
by Carla C. C. R. de Carvalho, Raquel Teixeira and Pedro Fernandes
Antibiotics 2020, 9(9), 544; https://doi.org/10.3390/antibiotics9090544 - 27 Aug 2020
Cited by 5 | Viewed by 3335
Abstract
Mycobacterium vaccae is being considered as an adjuvant to antituberculosis therapy, tested for the treatment of autoimmune diseases, and as an anti-depressive agent. This bacterium is ubiquitous in the environment and the widespread use of disinfectants and sanitisers may lead to its adaptation [...] Read more.
Mycobacterium vaccae is being considered as an adjuvant to antituberculosis therapy, tested for the treatment of autoimmune diseases, and as an anti-depressive agent. This bacterium is ubiquitous in the environment and the widespread use of disinfectants and sanitisers may lead to its adaptation to these compounds. In the present study, M. vaccae cells adapted to these compounds mainly by making adjustments in their lipid composition and net surface charge. The modifications in the lipid composition led to changes in membrane permeability which resulted in increased tolerance towards levofloxacin, thioridazine, and omeprazole. Full article
(This article belongs to the Special Issue Discovery of Novel Antibiotics)
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15 pages, 2795 KiB  
Article
GC-MS Profile and Enhancement of Antibiotic Activity by the Essential Oil of Ocotea odorífera and Safrole: Inhibition of Staphylococcus aureus Efflux Pumps
by Ray S. Almeida, Priscilla R. Freitas, Ana Carolina J. Araújo, Irwin R. Alencar Menezes, Eduardo L. Santos, Saulo R. Tintino, Talysson F. Moura, Jaime R. Filho, Vitória A. Ferreira, Ana Cristina A. Silva, Luiz E. Silva, Wanderlei do Amaral, Cícero Deschamps, Marcello Iriti and Henrique D. Melo Coutinho
Antibiotics 2020, 9(5), 247; https://doi.org/10.3390/antibiotics9050247 - 12 May 2020
Cited by 32 | Viewed by 5232
Abstract
Considering the evidence that essential oils, as well as safrole, could modulate bacterial growth in different resistant strains, this study aims to characterize the phytochemical profile and evaluate the antibacterial and antibiotic-modulating properties of the essential oil Ocotea odorífera (EOOO) and safrole against [...] Read more.
Considering the evidence that essential oils, as well as safrole, could modulate bacterial growth in different resistant strains, this study aims to characterize the phytochemical profile and evaluate the antibacterial and antibiotic-modulating properties of the essential oil Ocotea odorífera (EOOO) and safrole against efflux pump (EP)-carrying strains. The EOOO was extracted by hydrodistillation, and the phytochemical analysis was performed by gas chromatography coupled to mass spectrometry (GC-MS). The antibacterial and antibiotic-modulating activities of the EOOO and safrole against resistant strains of Staphylococcus aureus, Escherichia coli and Pseudomonas aeruginosa were analyzed through the broth microdilution method. The EP-inhibiting potential of safrole in association with ethidium bromide or antibiotics was evaluated using the S. aureus 1199B and K2068 strains, which carry genes encoding efflux proteins associated with antibiotic resistance to norfloxacin and ciprofloxacin, respectively. A reduction in the MIC of ethidium bromide or antibiotics was used as a parameter of EP inhibition. The phytochemical analysis identified 16 different compounds in the EOOO including safrole as the principal constituent. While the EOOO and safrole exerted clinically relevant antibacterial effects against S. aureus only, they potentiated the antibacterial activity of norfloxacin against all strains evaluated by our study. The ethidium bromide and antibiotic assays using the strains of S. aureus SA1119B and K2068, as well as molecular docking analysis, indicated that safrole inhibits the NorA and MepA efflux pumps in S. aureus. In conclusion, Ocotea odorifera and safrole presented promising antibacterial and antibiotic-enhancing properties, which should be explored in the development of drugs to combat antibacterial resistance, especially in strains bearing genes encoding efflux proteins. Full article
(This article belongs to the Special Issue Discovery of Novel Antibiotics)
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Review

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20 pages, 2181 KiB  
Review
Technologies for High-Throughput Identification of Antibiotic Mechanism of Action
by Bernardo Ribeiro da Cunha, Paulo Zoio, Luís P. Fonseca and Cecília R. C. Calado
Antibiotics 2021, 10(5), 565; https://doi.org/10.3390/antibiotics10050565 - 12 May 2021
Cited by 11 | Viewed by 5151
Abstract
There are two main strategies for antibiotic discovery: target-based and phenotypic screening. The latter has been much more successful in delivering first-in-class antibiotics, despite the major bottleneck of delayed Mechanism-of-Action (MOA) identification. Although finding new antimicrobial compounds is a very challenging task, identifying [...] Read more.
There are two main strategies for antibiotic discovery: target-based and phenotypic screening. The latter has been much more successful in delivering first-in-class antibiotics, despite the major bottleneck of delayed Mechanism-of-Action (MOA) identification. Although finding new antimicrobial compounds is a very challenging task, identifying their MOA has proven equally challenging. MOA identification is important because it is a great facilitator of lead optimization and improves the chances of commercialization. Moreover, the ability to rapidly detect MOA could enable a shift from an activity-based discovery paradigm towards a mechanism-based approach. This would allow to probe the grey chemical matter, an underexplored source of structural novelty. In this study we review techniques with throughput suitable to screen large libraries and sufficient sensitivity to distinguish MOA. In particular, the techniques used in chemical genetics (e.g., based on overexpression and knockout/knockdown collections), promoter-reporter libraries, transcriptomics (e.g., using microarrays and RNA sequencing), proteomics (e.g., either gel-based or gel-free techniques), metabolomics (e.g., resourcing to nuclear magnetic resonance or mass spectrometry techniques), bacterial cytological profiling, and vibrational spectroscopy (e.g., Fourier-transform infrared or Raman scattering spectroscopy) were discussed. Ultimately, new and reinvigorated phenotypic assays bring renewed hope in the discovery of a new generation of antibiotics. Full article
(This article belongs to the Special Issue Discovery of Novel Antibiotics)
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