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Special Issue "New Drugs and Novel Cellular Targets against Tuberculosis"

A special issue of International Journal of Molecular Sciences (ISSN 1422-0067). This special issue belongs to the section "Molecular Microbiology".

Deadline for manuscript submissions: 31 October 2021.

Special Issue Editors

Prof. Dr. Maria Rosalia Pasca
E-Mail Website
Guest Editor
Department of Biology and Biotechnology “Lazzaro Spallanzani”, University of Pavia, 27100 Pavia, Italy
Interests: study of mechanism of action and of resistance of new drugs against Mycobacterium tuberculosis and Mycobacterium abscessus
Special Issues and Collections in MDPI journals
Dr. Vadim Makarov
E-Mail Website
Guest Editor
Bach Institute of Biochemistry, Research Center of Biotechnology of the Russian Academy of Sciences, 119071 Moscow, Russia
Interests: synthesis of new compounds against Mycobacterium tuberculosis and Mycobacterium abscessus
Special Issues and Collections in MDPI journals
Dr. Giulia Degiacomi
E-Mail Website
Guest Editor
Department of Biology and Biotechnology “Lazzaro Spallanzani”, University of Pavia, 27100 Pavia, Italy
Interests: study of mechanism of action and of resistance of new drugs against Mycobacterium tuberculosis and Mycobacterium abscessus
Special Issues and Collections in MDPI journals
Dr. Laurent Chiarelli
E-Mail Website
Guest Editor
Department of Biology and Biotechnology “Lazzaro Spallanzani”, University of Pavia, 27100 Pavia, Italy
Interests: study of mechanism of action and of resistance of new drugs against Mycobacterium tuberculosis and Mycobacterium abscessus
Special Issues and Collections in MDPI journals

Special Issue Information

Dear Colleagues,

Mycobacterium tuberculosis is the etiological agent of tuberculosis (TB), one of the most life-threatening communicable diseases, which causes 10 million new cases each year and costs an estimated 1.4 million lives globally, accordingly to the World Health Organization. The spread of drug-resistant M. tuberculosis strains is worrisome for both the current antitubercular therapy and also for drugs recently released on the market.

The target of ending TB by 2030, as stated in the Sustainable Development Goals of the United Nations, will not be achieved also due to the concomitant COVID-19 pandemic, which is draining economical resources. In fact, efforts to defeat this pandemic have fuelled a rise in other infectious diseases such as TB. In this context, the delivery of novel drugs and new cellular targets towards TB is more urgent than ever.

This Special Issue will focus on the recent findings in the antitubercular field as well as the discovery of new cellular targets. Authors are welcome to contribute original research articles and reviews concerning not only new drugs with novel mechanisms of action, but also anti-virulence approaches, and host targeted therapies and repurposed drugs against M. tuberculosis. All contributions must fit the purpose of this Special Issue and the journal. We hope that the discussion on the latest findings will stimulate the development of a future antitubercular regimen.

Prof. Dr. Maria Rosalia Pasca
Dr. Vadim Makarov
Dr. Giulia Degiacomi
Dr. Laurent Chiarelli
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. International Journal of Molecular Sciences is an international peer-reviewed open access semimonthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. There is an Article Processing Charge (APC) for publication in this open access journal. For details about the APC please see here. 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

  • tuberculosis
  • Mycobacterium tuberculosis
  • drug target
  • antitubercular compounds
  • regimen
  • anti-virulence
  • medicinal chemistry
  • host-directed therapies
  • antitubercular resistance
  • drug discovery

Published Papers (1 paper)

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Research

Article
Gran1: A Granulysin-Derived Peptide with Potent Activity against Intracellular Mycobacterium tuberculosis
Int. J. Mol. Sci. 2021, 22(16), 8392; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms22168392 - 04 Aug 2021
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Abstract
Granulysin is an antimicrobial peptide (AMP) expressed by human T-lymphocytes and natural killer cells. Despite a remarkably broad antimicrobial spectrum, its implementation into clinical practice has been hampered by its large size and off-target effects. To circumvent these limitations, we synthesized a 29 [...] Read more.
Granulysin is an antimicrobial peptide (AMP) expressed by human T-lymphocytes and natural killer cells. Despite a remarkably broad antimicrobial spectrum, its implementation into clinical practice has been hampered by its large size and off-target effects. To circumvent these limitations, we synthesized a 29 amino acid fragment within the putative cytolytic site of Granulysin (termed “Gran1”). We evaluated the antimicrobial activity of Gran1 against the major human pathogen Mycobacterium tuberculosis (Mtb) and a panel of clinically relevant non-tuberculous mycobacteria which are notoriously difficult to treat. Gran1 efficiently inhibited the mycobacterial proliferation in the low micro molar range. Super-resolution fluorescence microscopy and scanning electron microscopy indicated that Gran1 interacts with the surface of Mtb, causing lethal distortions of the cell wall. Importantly, Gran1 showed no off-target effects (cytokine release, chemotaxis, cell death) in primary human cells or zebrafish embryos (cytotoxicity, developmental toxicity, neurotoxicity, cardiotoxicity). Gran1 was selectively internalized by macrophages, the major host cell of Mtb, and restricted the proliferation of the pathogen. Our results demonstrate that the hypothesis-driven design of AMPs is a powerful approach for the identification of small bioactive compounds with specific antimicrobial activity. Gran1 is a promising component for the design of AMP-containing nanoparticles with selective activity and favorable pharmacokinetics to be pushed forward into experimental in vivo models of infectious diseases, most notably tuberculosis. Full article
(This article belongs to the Special Issue New Drugs and Novel Cellular Targets against Tuberculosis)
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Planned Papers

The below list represents only planned manuscripts. Some of these manuscripts have not been received by the Editorial Office yet. Papers submitted to MDPI journals are subject to peer-review.

Title 1: Hybrid Phosphorus-viologen-dendrimers as new soft nanoparticles. Design and properties

Title 2: hydrazides as architectures for novel anti-TB compounds

Title 3: Tuberculosis antimicrobials alter immunometabolic profiles and mitochondrial function in primary human macrophages stimulated with Mycobacterium Tuberculosis

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