Special Issue "Beating the Bugs: Alternative Approaches to Reverse Antibiotic Resistance in Infectious Bacterial Pathogens"

A special issue of Antibiotics (ISSN 2079-6382). This special issue belongs to the section "Mechanism and Evolution of Antibiotic Resistance".

Deadline for manuscript submissions: 31 January 2021.

Special Issue Editors

Prof. Sanjib Bhakta
Website SciProfiles
Guest Editor
Birkbeck, University of London,London, United Kingdom
Interests: Mycobacterium tuberculosis; antimicrobial resistance;drug discovery;validation of novel therapeutic targets; repurposing drugs
Dr. Arundhati Maitra
Website
Guest Editor
Birkbeck, University of London,London, United Kingdom.
Interests: Mycobacterium tuberculosis;antimicrobial resistance;drug discovery;validation of novel therapeutic targets;repurposing drugs

Special Issue Information

Dear Colleagues,

We are 30 years away from the dire prediction that antimicrobial resistance (AMR) will claim 10 million lives a year and cost the world 100 trillion USD. Over the last decade, industry and academia have collaborated and mobilised forces in preparation to avert this public health crisis however, these efforts are yet to have an effect on the global AMR trends. Currently, infections caused by ‘superbugs’ claim the lives of an estimated 700,000 worldwide. A large majority of these infections in caused by strains of Mycobacterium tuberculosis and the ESKAPE group of infectious bacterial pathogens comprising of Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa, and the Enterobacter species. Transmission of resistance and increasing resistance profiles of these organisms make their control and treatment extremely challenging in the current environment of limited drug options that are still effective against them.

With calls urging our attention towards tackling the post-antibiotic era, research and development has to stay ahead and at times pre-empt the evolution of these pathogens. It is time to diversify our approach by attacking the instrinsic mechanisms of drug resistance such as efflux pumps, formation of biofilms and the activity of drug modifying enzymes to name a few. Therefore, instead of the conventional route of targeting novel pathways wherein resistance is quick to develop, these approaches will serve to reverse resistance and potentiate currently available therapy.

In this Special Issue, we aim to highlight the importance of interdisciplinary approaches in accelerating new drug development and repurposing existing drugs.

We invite authors to send in their manuscripts in the areas of interest as highlighted below:

  • Importance of rational drug design vis-a-vis whole-cell evaluation of chemical libraries
  • Reversing resistance by affecting intrinsic mechanisms of resistance
    • β-lactamase inhibition
    • Efflux pump inhibition
    • Disruption of biofilm
    • Membrane permeabilisers
    • Development of drug carriers that increase uptake of antibiotics
  • Alternative therapeutic routes
    • Phage therapy
    • Therapeutic vaccine development

Manuscripts that further our understanding of antimicrobial resistance, means to reverse them, and novel approaches not in this list specifically, yet still falling within the scope of the Special Issue are also welcome.

Prof. Sanjib Bhakta
Dr. Arundhati Maitra
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 papers will be 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 1600 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

  • Mycobacterium tuberculosis
  • Antimicrobial resistance
  • Drug discovery
  • Validation of novel therapeutic targets
  • Repurposing drugs

Published Papers (2 papers)

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Research

Open AccessArticle
Antimicrobial and Efflux Pump Inhibitory Activity of Carvotacetones from Sphaeranthus africanus Against Mycobacteria
Antibiotics 2020, 9(7), 390; https://doi.org/10.3390/antibiotics9070390 - 08 Jul 2020
Abstract
Carvotacetones (1–7) isolated from Sphaeranthus africanus were screened for their antimycobacterial and efflux pump (EP) inhibitory potential against the mycobacterial model strains Mycobacterium smegmatis mc2 155, Mycobacterium aurum ATCC 23366, and Mycobacterium bovis BCG ATCC 35734. The minimum inhibitory concentrations [...] Read more.
Carvotacetones (1–7) isolated from Sphaeranthus africanus were screened for their antimycobacterial and efflux pump (EP) inhibitory potential against the mycobacterial model strains Mycobacterium smegmatis mc2 155, Mycobacterium aurum ATCC 23366, and Mycobacterium bovis BCG ATCC 35734. The minimum inhibitory concentrations (MICs) of the carvotacetones were detected through high-throughput spot culture growth inhibition (HT-SPOTi) and microbroth dilution assays. In order to assess the potential of the compounds 1 and 6 to accumulate ethidium bromide (EtBr) in M. smegmatis and M. aurum, a microtiter plate-based fluorometric assay was used to determine efflux activity. Compounds 1 and 6 were analyzed for their modulating effects on the MIC of EtBr and the antibiotic rifampicin (RIF) against M. smegmatis. Carvotacetones 1 and 6 had potent antibacterial effects on M. aurum and M. bovis BCG (MIC ≤ 31.25 mg/L) and could successfully enhance EtBr activity against M. smegmatis. Compound 1 appeared as the most efficient agent for impairing the efflux mechanism in M. smegmatis. Both compounds 1 and 6 were highly effective against M. aurum and M. bovis BCG. In particular, compound 1 was identified as a valuable candidate for inhibiting mycobacterial efflux mechanisms and as a promising adjuvant in the therapy of tuberculosis or other non-tubercular mycobacterial infections. Full article
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Open AccessArticle
3-(5-Nitrofuran-2-yl)prop-2-en-1-one Derivatives, with Potent Antituberculosis Activity, Inhibit A Novel Therapeutic Target, Arylamine N-acetyltransferase, in Mycobacteria
Antibiotics 2020, 9(7), 368; https://doi.org/10.3390/antibiotics9070368 - 01 Jul 2020
Abstract
In this study, the inhibitory potential of 3-(5-nitrofuran-2-yl)prop-2-en-1-one derivatives was evaluated against a panel of bacteria, as well as mammalian cell lines to determine their therapeutic index. In addition, we investigated the mechanism of antibiotic action of the derivatives to identify their therapeutic [...] Read more.
In this study, the inhibitory potential of 3-(5-nitrofuran-2-yl)prop-2-en-1-one derivatives was evaluated against a panel of bacteria, as well as mammalian cell lines to determine their therapeutic index. In addition, we investigated the mechanism of antibiotic action of the derivatives to identify their therapeutic target. We discovered compound 2 to be an extremely potent inhibitor of Mycobacterium tuberculosis H37Rv growth (MIC: 0.031 mg/L) in vitro, performing better than the currently used first-line antituberculosis drugs such as isoniazid, rifampicin, ethambutol, and pretomanid in vitro. Furthermore, compound 3 was equipotent to pretomanid against a multidrug-resistant M. tuberculosis clinical isolate. The derivatives were selective and bactericidal towards slow-growing mycobacteria. They showed low cytotoxicity towards murine RAW 264.7 and human THP-1 cell lines, with high selectivity indices. Compound 1 effectively eliminated the intracellular mycobacteria in a mycobacteria-infected macrophage model. The derivatives were assessed for their potential to inhibit mycobacterial arylamine N-acetyltransferase (NAT) and were identified as good inhibitors of recombinant mycobacterial NAT, a novel target essential for the intracellular survival of M. tuberculosis. This study provided hits for designing new potent and selective antituberculosis leads, having mycobacterial NAT inhibition as their possible endogenous mechanisms of action. Full article
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