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Advances in Mycobacterial Diagnostics and Therapy

A special issue of International Journal of Molecular Sciences (ISSN 1422-0067). This special issue belongs to the section "Molecular Pathology, Diagnostics, and Therapeutics".

Deadline for manuscript submissions: closed (28 February 2024) | Viewed by 2348

Special Issue Editor


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Guest Editor
Institute of Infection and Immunology, St George’s, University of London, London SW17 0RE, UK
Interests: antimicrobial peptides; anticancer peptides; wound healing peptides; diagnostics of mycobacteria; neuro-immunology
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Special Issue Information

Dear Colleagues,

According to the World Health Organization (WHO), 10.6 million cases of tuberculosis (TB) were reported in 2021. Despite available treatment, 1.6 million people died from tuberculosis. The number of TB cases is decreasing, but not at the rate required for the WHO’s End TB strategy to be successful. In addition, a novel 6-monthly treatment for drug-resistant TB is now recommended by the WHO, reducing the treatment time for drug-resistant TB dramatically and helping to tackle resistant TB. Bovine TB is also still widely distributed in wildlife and farm animals, and can infect humans as well. Various other mycobacteria can also infect humans or animals and are challenging to treat.

New diagnostics, vaccinations, and treatments are important to further reduce the worldwide burden of TB and allow the End TB strategy to be successful. This Special Issue is dedicated to publishing new insights into diagnostic approaches and therapies for all mycobacteria. Papers published in the IJMS (International Journal of Molecular Sciences) are encouraged to include results at the molecular level. As a consequence, clinical research and survey studies are not suitable for the IJMS.

We look forward to receiving your valuable manuscripts.

Dr. Kai Hilpert
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. 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

  • mycobacteria
  • tuberculosis
  • diganostics
  • therapy
  • treatment
  • novel drugs

Published Papers (2 papers)

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Research

23 pages, 2844 KiB  
Article
Specific Cationic Antimicrobial Peptides Enhance the Recovery of Low-Load Quiescent Mycobacterium tuberculosis in Routine Diagnostics
by Tim J. Bull, Tulika Munshi, Paula M. Lopez-Perez, Andy C. Tran, Catherine Cosgrove, Angela Bartolf, Melissa Menichini, Laura Rindi, Lena Parigger, Nermina Malanovic, Karl Lohner, Carl J. H. Wang, Anam Fatima, Lisandra L. Martin, Semih Esin, Giovanna Batoni and Kai Hilpert
Int. J. Mol. Sci. 2023, 24(24), 17555; https://doi.org/10.3390/ijms242417555 - 16 Dec 2023
Cited by 2 | Viewed by 931
Abstract
The culture confirmation of Mycobacterium tuberculosis (MTB) remains the gold standard for the diagnosis of Tuberculosis (TB) with culture conversion representing proof of cure. However, over 40% of TB samples fail to isolate MTB even though many patients remain infectious due to the [...] Read more.
The culture confirmation of Mycobacterium tuberculosis (MTB) remains the gold standard for the diagnosis of Tuberculosis (TB) with culture conversion representing proof of cure. However, over 40% of TB samples fail to isolate MTB even though many patients remain infectious due to the presence of viable non-culturable forms. Previously, we have shown that two short cationic peptides, T14D and TB08L, induce a hormetic response at low concentrations, leading to a stimulation of growth in MTB and the related animal pathogen Mycobacterium bovis (bTB). Here, we examine these peptides showing they can influence the mycobacterial membrane integrity and function through membrane potential reduction. We also show this disruption is associated with an abnormal reduction in transcriptomic signalling from specific mycobacterial membrane sensors that normally monitor the immediate cellular environment and maintain the non-growing phenotype. We observe that exposing MTB or bTB to these peptides at optimal concentrations rapidly represses signalling mechanisms maintaining dormancy phenotypes, which leads to the promotion of aerobic metabolism and conversion into a replicative phenotype. We further show a practical application of these peptides as reagents able to enhance conventional routine culture methods by stimulating mycobacterial growth. We evaluated the ability of a peptide-supplemented sample preparation and culture protocol to isolate the MTB against a gold standard routine method tested in parallel on 255 samples from 155 patients with suspected TB. The peptide enhancement increased the sample positivity rate by 46% and decreased the average time to sample positivity of respiratory/faecal sampling by seven days. The most significant improvements in isolation rates were from sputum smear-negative low-load samples and faeces. The peptide enhancement increased sampling test sensitivity by 19%, recovery in samples from patients with a previously culture-confirmed TB by 20%, and those empirically treated for TB by 21%. We conclude that sample decontamination and culture enhancement with D-enantiomer peptides offer good potential for the much-needed improvement of the culture confirmation of TB. Full article
(This article belongs to the Special Issue Advances in Mycobacterial Diagnostics and Therapy)
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15 pages, 12711 KiB  
Article
A Comparative Study on the Mechanism of Delayed-Type Hypersensitivity Mediated by the Recombinant Mycobacterium tuberculosis Fusion Protein ESAT6-CFP10 and Purified Protein Derivative
by Xiaonan Guo, Weixin Du, Junli Li, Jiaxin Dong, Xiaobing Shen, Cheng Su, Aihua Zhao, Yongge Wu and Miao Xu
Int. J. Mol. Sci. 2023, 24(23), 16612; https://doi.org/10.3390/ijms242316612 - 22 Nov 2023
Cited by 1 | Viewed by 955
Abstract
While purified protein derivative (PPD) is commonly used as skin diagnostic reagent for tuberculosis (TB) infection, it cannot distinguish effectively Bacillus Calmette–Guérin (BCG) vaccination from Mycobacterium tuberculosis (MTB) complex and nontuberculous mycobacteria infection. The new skin reagent ESAT6-CFP10 (EC) has favorable sensitivity and [...] Read more.
While purified protein derivative (PPD) is commonly used as skin diagnostic reagent for tuberculosis (TB) infection, it cannot distinguish effectively Bacillus Calmette–Guérin (BCG) vaccination from Mycobacterium tuberculosis (MTB) complex and nontuberculous mycobacteria infection. The new skin reagent ESAT6-CFP10 (EC) has favorable sensitivity and specificity, which can overcome limitations associated with PPD. At present, EC skin test reactions are mainly characterized by erythema, while PPD mainly causes induration. We conducted a comparative study on the potential differences between EC-induced erythema and PPD-induced induration using a guinea pig model. The size of EC-dependent erythema was similar to that of PPD-induced induration, and an inflammatory response characterized by the infiltration of monocytes, macrophages and lymphocytes, as well as tissue damage, appeared at the injection site. The lymphocytes included CD4+ T and CD8+ T cells, which released IFN-γ as the main cytokine. Both EC erythema and PPD induration could lead to increased levels of acute-phase proteins, and the differential pathways were similar, thus indicating that the main induced immune pathways were similar. The above results indicated that erythema produced by EC could generate the main delayed-type hypersensitivity (DTH) response characteristic of PPD induration, thereby suggesting that erythema might also have a certain diagnostic significance and provide a possible theoretical basis for its use as a diagnostic indicator for detecting MTB infection. Full article
(This article belongs to the Special Issue Advances in Mycobacterial Diagnostics and Therapy)
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