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Antibiotics
Special Issues
Advances in the Discovery of Novel Antibiotics
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Advances in the Discovery of Novel Antibiotics

A special issue of Antibiotics (ISSN 2079-6382). This special issue belongs to the section "The Global Need for Effective Antibiotics".

Deadline for manuscript submissions: closed (31 July 2022) | Viewed by 9344

Special Issue Editor

Dr. Younes Smani

E-Mail Website
Guest Editor
Institute of Biomedicine of Seville, University of Seville, 41013 Seville, Spain
Interests: antimicrobial resistance; bacterial pathogenesis; antibiotics; repurposing drug; non-traditional approaches
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Compounding the problem of antimicrobial resistance is the immediate threat of a reduction in the discovery and development of new antibiotics, the dangers of which have recently been made clear by the World Health Organization (WHO) and other institutions in Europe. Consequently, a perfect storm is converging with regard to bacterial infections: antimicrobial resistance is increasing, whereas there has been a decrease in the development of novel antibiotics. New policies and actions are necessary to avoid the figures predicted for 2050, which attribute ten million deaths worldwide to antimicrobial resistance. Therefore, the development of non-traditional therapeutic strategies such as repurposed drugs, immunomodulators, bacteriophages, and antivirulence therapeutics for use alone or together with clinically relevant antibiotics has become exigent. In this environment, repurposing therapeutic drugs has received considerable attention. Despite this interest, only few repurposing drug trials are in advanced preclinical or clinical development. The goal of this Special Issue is to systematically provide an overview on the scientific evidence on the therapeutic potential of repurposing drugs against Gram-negative and Gram-positive bacteria. In specific, we aim to:

i) Discuss the therapeutic potential of this drug class;

ii) Identify their potential targets and their mechanisms of action, including DNA, RNA and proteins inhibitors, quorum sensing regulators, biofilm formation inhibitors and disruptors, drugs that interact with the cell membrane and iron metabolism, and host immune system modulators, among others;

iii) Summarize the outcomes of advanced preclinical trials for treating bacterial infections.

We welcome researchers to submit original research, reviews, or perspectives focusing on repurposing drugs for treatment against bacteria.

Dr. Younes Smani
Guest Editor

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

  • novel antibiotic drugs
  • treatment
  • antimicrobial resistance
  • infection
  • bacteria
  • non-traditional approaches

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Published Papers (3 papers)

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14 pages, 1533 KiB  
Article
In Vitro Screening of a 1280 FDA-Approved Drugs Library against Multidrug-Resistant and Extensively Drug-Resistant Bacteria
by Lucie Peyclit, Sophie Alexandra Baron, Linda Hadjadj and Jean-Marc Rolain
Antibiotics 2022, 11(3), 291; https://doi.org/10.3390/antibiotics11030291 - 22 Feb 2022
Cited by 6 | Viewed by 3210
Abstract
Alternative strategies against multidrug-resistant (MDR) bacterial infections are suggested to clinicians, such as drug repurposing, which uses rapidly available and marketed drugs. We gathered a collection of MDR bacteria from our hospital and performed a phenotypic high-throughput screening with a 1280 FDA-approved drug [...] Read more.
Alternative strategies against multidrug-resistant (MDR) bacterial infections are suggested to clinicians, such as drug repurposing, which uses rapidly available and marketed drugs. We gathered a collection of MDR bacteria from our hospital and performed a phenotypic high-throughput screening with a 1280 FDA-approved drug library. We used two Gram positive (Enterococcus faecium P5014 and Staphylococcus aureus P1943) and six Gram negative (Acinetobacter baumannii P1887, Klebsiella pneumoniae P9495, Pseudomonas aeruginosa P6540, Burkholderia multivorans P6539, Pandoraea nosoerga P8103, and Escherichia coli DSM105182 as the reference and control strain). The selected MDR strain panel carried resistance genes or displayed phenotypic resistance to last-line therapies such as carbapenems, vancomycin, or colistin. A total of 107 compounds from nine therapeutic classes inhibited >90% of the growth of the selected Gram negative and Gram positive bacteria at a drug concentration set at 10 µmol/L, and 7.5% were anticancer drugs. The common hit was the antiseptic chlorhexidine. The activity of niclosamide, carmofur, and auranofin was found against the selected methicillin-resistant S. aureus. Zidovudine was effective against colistin-resistant E. coli and carbapenem-resistant K. pneumoniae. Trifluridine, an antiviral, was effective against E. faecium. Deferoxamine mesylate inhibited the growth of XDR P. nosoerga. Drug repurposing by an in vitro screening of a drug library is a promising approach to identify effective drugs for specific bacteria. Full article
(This article belongs to the Special Issue Advances in the Discovery of Novel Antibiotics)
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35 pages, 11057 KiB  
Article
Repurposing α-Adrenoreceptor Blockers as Promising Anti-Virulence Agents in Gram-Negative Bacteria
by Ahmad J. Almalki, Tarek S. Ibrahim, Sameh S. Elhady, Khaled M. Darwish and Wael A. H. Hegazy
Antibiotics 2022, 11(2), 178; https://doi.org/10.3390/antibiotics11020178 - 29 Jan 2022
Cited by 26 | Viewed by 3259
Abstract
Antimicrobial resistance is among the world’s most urgent public health problems. Diminishing of the virulence of bacteria is a promising approach to decrease the development of bacterial resistance. Quorum sensing (QS) systems orchestrate the bacterial virulence in inducer–receptors manner. Bacteria can spy on [...] Read more.
Antimicrobial resistance is among the world’s most urgent public health problems. Diminishing of the virulence of bacteria is a promising approach to decrease the development of bacterial resistance. Quorum sensing (QS) systems orchestrate the bacterial virulence in inducer–receptors manner. Bacteria can spy on the cells of the host by sensing adrenergic hormones and other neurotransmitters, and in turn, these neurotransmitters can induce bacterial pathogenesis. In this direction, α-adrenergic blockers were proposed as an anti-virulence agents through inhibiting the bacterial espionage. The current study aimed to explore the α-blockers’ anti-QS activities. Within comprehensive in silico investigation, the binding affinities of seven α-adrenoreceptor blockers were evaluated towards structurally different QS receptors. From the best docked α-blockers into QS receptors, terazosin was nominated to be subjected for further in vivo and in vitro anti-QS and anti-virulence activities against Chromobacterium violaceum and Pseudomonas aeruginosa. Terazosin showed a significant ability to diminish the QS-controlled pigment production in C. violaceum. Moreover, Terazosin decreased the P. aeruginosa biofilm formation and down-regulated its QS-encoding genes. Terazosin protected mice from the P. aeruginosa pathogenesis. In conclusion, α-adrenergic blockers are proposed as promising anti-virulence agents as they hinder QS receptors and inhibit bacterial espionage. Full article
(This article belongs to the Special Issue Advances in the Discovery of Novel Antibiotics)
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7 pages, 625 KiB  
Brief Report
Quercetin Is a Novel Inhibitor of the Choline Kinase of Streptococcus pneumoniae
by Tahl Zimmerman and Salam A. Ibrahim
Antibiotics 2022, 11(9), 1272; https://doi.org/10.3390/antibiotics11091272 - 19 Sep 2022
Cited by 2 | Viewed by 2094
Abstract
The effectiveness of current antimicrobial methods for addressing for food-borne Gram-positive pathogens has dropped with the emergence of resistant strains. Consequently, new methods for addressing Gram-positive strains have to be developed continuously. This includes establishing novel targets for antimicrobial discovery efforts. Eukaryotic choline [...] Read more.
The effectiveness of current antimicrobial methods for addressing for food-borne Gram-positive pathogens has dropped with the emergence of resistant strains. Consequently, new methods for addressing Gram-positive strains have to be developed continuously. This includes establishing novel targets for antimicrobial discovery efforts. Eukaryotic choline kinases have been highly developed as drug targets for the treatment of cancer, rheumatoid arthritis, malaria and many other conditions and diseases. Recently, choline kinase (ChoK) has been proposed as a drug target for Gram-positive species generally. The aim of this work was to discover novel, natural sources of inhibitors for bacterial ChoK from tea extracts. We report the first natural bacterial ChoK inhibitor with antimicrobial activity against Streptococcus pneumoniae: quercetin. Full article
(This article belongs to the Special Issue Advances in the Discovery of Novel Antibiotics)
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