Research for New Drugs against Tuberculosis and Other Mycobacterial Diseases

Topic Information

Dear Colleagues,

Mycobacterium tuberculosis is the major etiological agent for tuberculosis (TB), an infectious disease. TB is the leading cause of single pathogen infection-related deaths with more than 4000 TB-related deaths reported every day worldwide. In 2019, approximately 10 million individuals were diagnosed with TB and an estimated 25% of the population suffered from latent TB. The World Health Organization (WHO) has aimed to reduce TB-related deaths and infections by 90% and 80% by 2030, respectively, when compared with those reported in 2015. To achieve this goal, novel safe, and effective antibiotics must be developed against intracellular, non-replicant, and resistant strains. On the other hand Non-tuberculous mycobacteria (NTM) are ubiquitously present in the environment, but NTM diseases occur infrequently. NTM are generally considered to be less virulent than Mycobacterium tuberculosis, however, these organisms can cause diseases in both immunocompromised and immunocompetent hosts. Therefore, there is an urgent need to develop novel drugs for effectively treating MDR-TB, and NTM decreasing the treatment duration, and minimizing the toxicity and cost of the drugs. This Research Topic requires the coordinated effort of multiple scientific disciplines as microbiology, pharmacology, chemistry, medical and correlated. We welcome your contributions on all aspects of novel drugs for treating MDR-TB in this Topic.

Prof. Dr. Fernando Rogério Pavan
Prof. Dr. Alzir Azevedo Batista
Dr. Adelino Vieira de Godoy Netto
Dr. Daniela Fernandes Ramos
Topic Editors

Keywords

Participating Journals

Journal Name	Impact Factor	CiteScore	Launched Year	First Decision (median)	APC
Biomedicines biomedicines	4.7	3.7	2013	15.4 Days	CHF 2600
Future Pharmacology futurepharmacol	-	-	2021	20.5 Days	CHF 1000
Journal of Clinical Medicine jcm	3.9	5.4	2012	17.9 Days	CHF 2600
Pharmaceutics pharmaceutics	5.4	6.9	2009	14.2 Days	CHF 2900
Tropical Medicine and Infectious Disease tropicalmed	2.9	4.1	2016	19.4 Days	CHF 2700

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Published Papers (3 papers)

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All Biomedicines Future Pharmacology JCM Pharmaceutics TropicalMed

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27 pages, 7084 KiB  

Open AccessReview

Moles of Molecules against Mycobacterium abscessus: A Review of Current Research

by Mario Cocorullo, Christian Bettoni, Sara Foiadelli and Giovanni Stelitano

Future Pharmacol. 2023, 3(3), 637-663; https://doi.org/10.3390/futurepharmacol3030041 - 11 Sep 2023

Viewed by 940

Abstract

Mycobacterium abscessus is an emerging opportunistic pathogen that infects mainly the respiratory tract of individuals with pre-existing clinical pictures. In recent years, the incidence of infections of this microorganism has risen, in particular in patients with cystic fibrosis, leading to an exacerbation of [...] Read more.

Mycobacterium abscessus is an emerging opportunistic pathogen that infects mainly the respiratory tract of individuals with pre-existing clinical pictures. In recent years, the incidence of infections of this microorganism has risen, in particular in patients with cystic fibrosis, leading to an exacerbation of their conditions. The actual therapeutic regimen has low efficacy and is extended for long periods since it is mainly based on a combination of repurposed drugs, generally from treatments of Mycobacterium tuberculosis infections. For this reason, it is necessary to develop new drugs or alternative strategies in order to improve the efficacy and shorten the time of treatments. This review aims to give an overview of drugs in the pre-clinical and clinical phases of evaluation against M. abscessus and the molecules that have been in development for the past five years in the early drug-discovery phase. Full article

(This article belongs to the Topic Research for New Drugs against Tuberculosis and Other Mycobacterial Diseases)

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13 pages, 1339 KiB  

Open AccessCommunication

Single Turnover of Transient of Reactants Supports a Complex Interplay of Conformational States in the Mode of Action of Mycobacterium tuberculosis Enoyl Reductase

by Leonardo Kras Borges Martinelli, Mariane Rotta, Cristiano Valim Bizarro, Pablo Machado and Luiz Augusto Basso

Future Pharmacol. 2023, 3(2), 379-391; https://doi.org/10.3390/futurepharmacol3020023 - 30 Mar 2023

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Abstract

The enoyl reductase from Mycobacterium tuberculosis (MtInhA) was shown to be a major target for isoniazid, the most prescribed first-line anti-tuberculosis agent. The MtInhA (EC 1.3.1.9) protein catalyzes the hydride transfer from the 4S hydrogen of β-NADH to carbon-3 [...] Read more.

The enoyl reductase from Mycobacterium tuberculosis (MtInhA) was shown to be a major target for isoniazid, the most prescribed first-line anti-tuberculosis agent. The MtInhA (EC 1.3.1.9) protein catalyzes the hydride transfer from the 4S hydrogen of β-NADH to carbon-3 of long-chain 2-trans-enoyl thioester substrates (enoyl-ACP or enoyl-CoA) to yield NAD⁺ and acyl-ACP or acyl-CoA products. The latter are the long carbon chains of the meromycolate branch of mycolic acids, which are high-molecular-weight α-alkyl, β-hydroxy fatty acids of the mycobacterial cell wall. Here, stopped-flow measurements under single-turnover experimental conditions are presented for the study of the transient of reactants. Single-turnover experiments at various enzyme active sites were carried out. These studies suggested isomerization of the MtInhA:NADH binary complex in pre-incubation and positive cooperativity that depends on the number of enzyme active sites occupied by the 2-trans-dodecenoyl-CoA (DD-CoA) substrate. Stopped-flow results for burst analysis indicate that product release does not contribute to the rate-limiting step of the MtInhA-catalyzed chemical reaction. The bearings that the results presented herein have on function-based anti-tuberculosis drug design are discussed. Full article

(This article belongs to the Topic Research for New Drugs against Tuberculosis and Other Mycobacterial Diseases)

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12 pages, 1646 KiB  

Open AccessArticle

Latent Tuberculosis: A Promising New Compound to Treat Non-Replicating and Intramacrophagic Mycobacteria

by Débora Leite Campos, Fernanda Manaia Demarqui, Mariana Cristina Solcia, Paula Carolina de Souza, Pedro Ivo da Silva Maia, Victor Marcelo Deflon and Fernando Rogério Pavan

Biomedicines 2022, 10(10), 2398; https://doi.org/10.3390/biomedicines10102398 - 26 Sep 2022

Cited by 2 | Viewed by 1362

Abstract

As a biologic reservoir of Mycobacterium tuberculosis (M. tb), one-quarter of the world population is infected with the well-known latent tuberculosis (LTBI). About 5–10% of LTBI patients will progress to active disease in the first years after primary infection and, despite [...] Read more.

As a biologic reservoir of Mycobacterium tuberculosis (M. tb), one-quarter of the world population is infected with the well-known latent tuberculosis (LTBI). About 5–10% of LTBI patients will progress to active disease in the first years after primary infection and, despite using the recommended treatment, 20% can still reactivate the infection. A new LTBI treatment could minimize adverse effects and antibiotic resistance that can occur when the same drug is used to treat the latent and active disease. New hydrazones were evaluated, and they showed great inhibitory activity against intramacrophagic and non-replicating M. tb, commonly found at this stage of infection, in addition to bactericidal and narrow-spectrum activity. When tested against eukaryotic cells, the hydrazones showed great safety at different exposure times. In vitro, these compounds performed better than isoniazid and could be considered new candidates for LTBI treatment, which may promote greater engagement in its prescription and adherence. Full article

(This article belongs to the Topic Research for New Drugs against Tuberculosis and Other Mycobacterial Diseases)

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