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Biomedicines
Special Issues
Tuberculosis and Latent Tuberculosis Infection: Molecular Basis and Translational Research
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Tuberculosis and Latent Tuberculosis Infection: Molecular Basis and Translational Research

A special issue of Biomedicines (ISSN 2227-9059). This special issue belongs to the section "Molecular and Translational Medicine".

Deadline for manuscript submissions: closed (30 September 2023) | Viewed by 8018

Special Issue Editors

Dr. Jann-Yuan Wang

E-Mail Website
Guest Editor
1. Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan
2. Department of Internal Medicine, National Taiwan University College of Medicine, Taipei, Taiwan
Interests: tuberculosis; nontuberculous mycobacterium; latent tuberculosis infection; chronic pulmonary aspergillosis
Dr. Horng-Yunn Dou

E-Mail Website
Guest Editor
Institute of Infectious Diseases and Vaccinology, National Health Research Institutes, Miaoli County, Taiwan
Interests: tuberculosis; immune response; molecular diagnosis; molecular epidemiology
Dr. Abhishek Mishra

E-Mail Website
Guest Editor
Houston Methodist Research Institute, Houston, TX, USA
Interests: mycobacterium tuberculosis; autophagy; infectious disease; genomic medicine; vaccine; free radical biology; microbiology; biochemistry; nanotechnology; genomics proteomics; immunology

Special Issue Information

Dear Colleagues,

Though effective treatment has been available for more than sixty years, tuberculosis (TB) remains one of the deadly infectious diseases worldwide. Early diagnosis and treatment are crucial to prevent transmission and reduce mortality. However, many aspects of TB pathogenesis and transmission are still unclear, preventing accurate diagnosis and effective intervention. More translational research works for the management of TB are urgently needed. Another critical element in TB control is preventive therapy for latent TB infection (LTBI). Correct diagnosis and safe, short treatment both contribute to the effectiveness of LTBI intervention programs and public acceptance. With the introduction of interferon-gamma release assay (IGRA) and rifapentine, a long-acting rifamycin drug, there has been tremendous improvement in the implementation of LTBI programs. However, current clinical practice for LTBI is far from optimal. There are still many research gaps concerning the molecular basis of host immune response against TB bacilli and adverse drug reactions, as well as short, safe, and personalized treatment.

Dr. Jann-Yuan Wang
Dr. Horng-Yunn Dou
Dr. Abhishek Mishra
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. Biomedicines 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 2600 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

  • adverse reaction
  • biological pathway
  • gene signature
  • host immunity
  • latent tuberculosis infection
  • microbial virulence
  • molecular epidemiology
  • tuberculosis
  • preventive therapy

Published Papers (3 papers)

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Research

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21 pages, 5425 KiB  
Article
Tuberculosis Severity Predictive Model Using Mtb Variants and Serum Biomarkers in a Colombian Cohort of APTB Patients
by Juan C. Ocampo, Juan F. Alzate, Luis F. Barrera and Andres Baena
Biomedicines 2023, 11(12), 3110; https://doi.org/10.3390/biomedicines11123110 - 22 Nov 2023
Viewed by 1754
Abstract
Currently, tuberculosis (TB) is a bacterial infection caused by Mycobacterium tuberculosis (Mtb) that primarily affects the lungs. The severity of active pulmonary TB (APTB) is an important determinant of transmission, morbidity, mortality, disease experience, and treatment outcomes. Several publications have shown a high [...] Read more.
Currently, tuberculosis (TB) is a bacterial infection caused by Mycobacterium tuberculosis (Mtb) that primarily affects the lungs. The severity of active pulmonary TB (APTB) is an important determinant of transmission, morbidity, mortality, disease experience, and treatment outcomes. Several publications have shown a high prevalence of disabling complications in individuals who have had severe APTB. Furthermore, certain strains of Mtb were associated with more severe disease outcomes. The use of biomarkers to predict severe APTB patients who are candidates for host-directed therapies, due to the high risk of developing post-tuberculous lung disease (PTLD), has not yet been implemented in the management of TB patients. We followed 108 individuals with APTB for 6 months using clinical tools, flow cytometry, and whole-genome sequencing (WGS). The median age of the study population was 26.5 years, and the frequency of women was 53.7%. In this study, we aimed to identify biomarkers that could help us to recognize individuals with APTB and improve our understanding of the immunopathology in these individuals. In this study, we conducted a follow-up on the treatment progress of 121 cases of APTB. The follow-up process commenced at the time of diagnosis (T0), continued with a control visit at 2 months (T2), and culminated in an exit appointment at 6 months following the completion of medical treatment (T6). People classified with severe APTB showed significantly higher levels of IL-6 (14.7 pg/mL; p < 0.05) compared to those with mild APTB (7.7 pg/mL) at T0. The AUCs for the ROC curves and the Matthews correlation coefficient values (MCC) demonstrate correlations ranging from moderate to very strong. We conducted WGS on 88 clinical isolates of Mtb, and our analysis revealed a total of 325 genes with insertions and deletions (Indels) within their coding regions when compared to the Mtb H37Rv reference genome. The pattern of association was found between serum levels of CHIT1 and the presence of Indels in Mtb isolates from patients with severe APTB. A key finding in our study was the high levels of CHIT1 in severe APTB patients. We identified a biomarker profile (IL-6, IFN-γ, IL-33, and CHIT1) that allows us to identify individuals with severe APTB, as well as the identification of a panel of polymorphisms (125) in clinical isolates of Mtb from individuals with severe APTB. Integrating these findings into a predictive model of severity would show promise for the management of APTB patients in the future, to guide host-directed therapy and reduce the prevalence of PTLD. Full article
(This article belongs to the Special Issue Tuberculosis and Latent Tuberculosis Infection: Molecular Basis and Translational Research)
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11 pages, 1355 KiB  
Article
The Dynamic Change of Immune Checkpoints and CD14+ Monocytes in Latent Tuberculosis Infection
by Ping-Huai Wang, Ming-Fang Wu, Chi-Yu Hsu, Shu-Yung Lin, Ya-Nan Chang, Ho-Shen Lee, Yu-Feng Wei and Chin-Chung Shu
Biomedicines 2021, 9(10), 1479; https://doi.org/10.3390/biomedicines9101479 - 15 Oct 2021
Cited by 11 | Viewed by 1846
Abstract
Controlling latent tuberculosis infection (LTBI) is important for preventing tuberculosis (TB). However, the immune regulation of LTBI remains uncertain. Immune checkpoints and CD14+ monocytes are pivotal for immune defense but have been scarcely studied in LTBI. We prospectively enrolled participants with LTBI and [...] Read more.
Controlling latent tuberculosis infection (LTBI) is important for preventing tuberculosis (TB). However, the immune regulation of LTBI remains uncertain. Immune checkpoints and CD14+ monocytes are pivotal for immune defense but have been scarcely studied in LTBI. We prospectively enrolled participants with LTBI and controls from January 2017 to December 2019. We measured their CD14+ monocytes and the expression of immune checkpoints, including programmed death-1 (PD-1), cytotoxic T-lymphocyte-associated protein 4 (CTLA-4), and T cell immunoglobulin mucin domain-containing-3 (TIM3) on T lymphocytes in peripheral blood mononuclear cells before and after LTBI treatment. A total of 87 subjects were enrolled, including 29 IGRA-negative healthy controls (HC), 58 in the LTBI group (19 without chronic kidney disease (non-CKD), and 39 with end-stage renal disease (ESRD)). All PD-1, CTLA-4, and TIM3 on lymphocytes and monocytes were higher in the LTBI group than that in the HC group. Total CD14+ monocytes were higher and PD-L2+CD14+ over monocytes were lower in patients with LTBI-non-CKD than that in the HC group. After LTBI treatment, CD14+ monocytes, TIM3+ on CD4+ and monocytes, and CTLA-4 on lymphocytes decreased significantly. Multivariable logistic regression indicated that CD14+ monocytes was an independent factor for LTBI-non-CKD from the HC group, whereas PD-L2+CD14+ monocytes and TIM3+ monocytes were significant for LTBI-ESRD from the HC group. In conclusion, LTBI status was associated with increasing CD14+ monocytes plus low PD-L2 expression. By contrast, increased expression of immune checkpoints over all immune cells might be due to Mycobacterium tuberculosis related immune exhaustion, which decreased after treatment. Full article
(This article belongs to the Special Issue Tuberculosis and Latent Tuberculosis Infection: Molecular Basis and Translational Research)
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Review

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15 pages, 2397 KiB  
Review
MmpL3 Inhibition as a Promising Approach to Develop Novel Therapies against Tuberculosis: A Spotlight on SQ109, Clinical Studies, and Patents Literature
by Mohd. Imran, Mandeep Kumar Arora, Anurag Chaudhary, Shah Alam Khan, Mehnaz Kamal, Manal Mutlaq Alshammari, Raghad Mohammad Alharbi, Nuha Abdullah Althomali, Ibrahim Mohammed Alzimam, Abdullah Ayed Alshammari, Bashair Hamed Alharbi, Amer Alshengeti, Abdulmonem A. Alsaleh, Shayea A. Alqahtani and Ali A. Rabaan
Biomedicines 2022, 10(11), 2793; https://doi.org/10.3390/biomedicines10112793 - 3 Nov 2022
Cited by 10 | Viewed by 3084
Abstract
Tuberculosis (TB) is accountable for considerable global morbidity and mortality. Effective TB therapy with multiple drugs completes in about six months. The longer duration of TB therapy challenges patient compliance and contributes to treatment collapse and drug resistance (DR) progress. Therefore, new medications [...] Read more.
Tuberculosis (TB) is accountable for considerable global morbidity and mortality. Effective TB therapy with multiple drugs completes in about six months. The longer duration of TB therapy challenges patient compliance and contributes to treatment collapse and drug resistance (DR) progress. Therefore, new medications with an innovative mechanism of action are desperately required to shorten the TB therapy’s duration and effective TB control. The mycobacterial membrane protein Large 3 (MmpL3) is a novel, mycobacteria-conserved and recognized promiscuous drug target used in the development of better treatments for multi-drug resistance TB (MDR-TB) and extensively drug-resistant TB (XDR-TB). This article spotlights MmpL3, the clinical studies of its inhibitor (SQ109), and the patent literature. The literature on MmpL3 inhibitors was searched on PubMed and freely available patent databases (Espacenet, USPTO, and PatentScope). SQ109, an analog of ethambutol (EMB), is an established MmpL3 inhibitor and has completed Phase 2b-3 clinical trials. Infectex and Sequella are developing orally active SQ109 in partnership to treat MDR pulmonary TB. SQ109 has demonstrated activity against drug-sensitive (DS) and drug-resistant (DR) Mycobacterium tuberculosis (Mtb) and a synergistic effect with isoniazid (INH), rifampicin (RIF), clofazimine (CFZ), and bedaquiline (BNQ). The combination of SQ109, clofazimine, bedaquiline, and pyrazinamide (PZA) has been patented due to its excellent anti-TB activity against MDR-TB, XDR-TB, and latent-TB. The combinations of SQ109 with other anti-TB drugs (chloroquine, hydroxychloroquine, and sutezolid) have also been claimed in the patent literature. SQ109 is more potent than EMB and could substitute EMB in the intensive stage of TB treatment with the three- or four-drug combination. Developing MmpL3 inhibitors is a promising approach to fighting the challenges associated with DS-TB and DR-TB. The authors foresee MmpL3 inhibitors such as SQ109 as future drugs for TB treatment. Full article
(This article belongs to the Special Issue Tuberculosis and Latent Tuberculosis Infection: Molecular Basis and Translational Research)
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