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Microorganisms
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Prevention, Treatment and Diagnosis of Tuberculosis, 2nd Edition
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Prevention, Treatment and Diagnosis of Tuberculosis, 2nd Edition

A special issue of Microorganisms (ISSN 2076-2607). This special issue belongs to the section "Public Health Microbiology".

Deadline for manuscript submissions: 31 December 2024 | Viewed by 6194

Special Issue Editor

Dr. Rogelio Hernández Pando

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Guest Editor
Sección de Patología Experimental, Departamento de Patología, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Mexico City 14080, Mexico
Interests: tuberculosis; anti-tuberculosis
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

This Special Issue is a continuation of our 2023 Special Issue "Prevention, Treatment and Diagnosis of Tuberculosis”.

Tuberculosis (TB) has been a prevalent infectious disease since ancient times and remains a major worldwide health problem. With 10 million active cases and 1.4 million deaths annually, TB morbidity represents the most significant number of incidences and human deaths attributable to a single bacterial agent. Its causal agent, Mycobacterium tuberculosis (Mtb), can survive in a latent state in infected individuals, thereby serving as a reservoir, awaiting reactivation that usually occurs in immune-suppressed individuals. According to the World Health Organization estimation, 2 billion people, almost one-quarter of the world’s population, are latent infected. From this vast population, it is estimated that 10% will reactivate progressive suffering disease. TB control has been severely limited by imperfect diagnostic testing. The gold-standard method of diagnosing TB is acid-fast bacilli (AFB) smear microscopy and sputum cultures for Mtb, followed by growth-based drug-susceptibility testing. The sensitivity of AFB is low and variable (ranges from 45% to 80%), is affected by specimen concentration and laboratory experience, and usually, these diagnostic testing takes months to complete. Molecular diagnostic testing for the detection of Mtb is rapid but complex and requires expensive equipment. Regarding TB prevention, the vaccine BCG (Bacillus Calmette-Guérin) is the most widely used vaccine in history but has proven insufficient for reversing this epidemic. The BCG vaccine has been outstandingly successful in preventing severe forms of TB (meningeal and miliary). Nonetheless, the vaccine presents considerable shortcomings in terms of preventing pulmonary TB, with considerable variability in efficacy, ranging from 0 to 75% in different regions of the world. Another significant problem is the continued emergence of multidrug-resistant (MDR) strains, which is currently considered a serious global health problem. The emergence of MDR strain is often associated with poor compliance due to the long, complex, toxic and expensive treatment. New therapeutic candidates should short the standard regimens and ideally be effective against MDR strains. Thus, new diagnostic methods, new vaccines and better anti-TB drugs and therapeutic strategies are urgently needed. In this Research Topic, we aim to provide a comprehensive overview of recent progress in the prevention, diagnosis and treatment of TB. We welcome the submission of Original Research, Reviews, and Perspective articles covering, but not limited to, the following sub-topics:

  • Novel methodologies for TB diagnosis.
  • Novel anti-TB drugs and therapeutic strategies, including immunotherapy.
  • Novel approaches in the design of new vaccines against TB.

Dr. Rogelio Hernández Pando
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. Microorganisms 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 2700 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

  • tuberculosis
  • anti-TB drugs
  • therapy
  • TB vaccines

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Published Papers (6 papers)

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Research

15 pages, 1548 KiB  
Article
Antimycobacterial Activity of Solid Lipid Microparticles Loaded with Ursolic Acid and Oleanolic Acid: In Vitro, In Vivo, and Toxicity Assessments
by Vinay Saini, Dulce Mata Espinosa, Alok Pandey, Vikas Dighe, Jorge Barrios Payán, Vithal Prasad Myneedu, Ivan Valdez Zarate, Dhanji P. Rajani, Lalit D. Anande, Rogelio Hernandez Pando and Rohit Srivastava
Microorganisms 2024, 12(11), 2140; https://doi.org/10.3390/microorganisms12112140 - 25 Oct 2024
Viewed by 828
Abstract
Ursolic acid (UA) and oleanolic acid (OA) are hydrophobic triterpenoid isomers with demonstrated anti-mycobacterial (Mtb) and immune-regulatory properties, although their poor solubility limits clinical use. We report the development of solid lipid microparticles (SLMs) as delivery vehicles for UA and OA and evaluate [...] Read more.
Ursolic acid (UA) and oleanolic acid (OA) are hydrophobic triterpenoid isomers with demonstrated anti-mycobacterial (Mtb) and immune-regulatory properties, although their poor solubility limits clinical use. We report the development of solid lipid microparticles (SLMs) as delivery vehicles for UA and OA and evaluate their anti-Mtb efficacy in vitro and in vivo, as well as their acute toxicity. SLMs measured 0.7–0.89 µM in size, with complete in vitro release of OA and UA at 40 and 32 h, respectively. The minimum inhibitory concentration (MIC) of SLMs loaded with OA and UA was 40 µg/mL SLMs + 20 µg/mL OA + 20 µg/mL UA for drug-sensitive Mtb and 80 µg/mL SLMs + 40 µg/mL OA + 40 µg/mL UA for multidrug-resistant (MDR) Mtb. These SLMs showed an efficient reduction in Mtb burden in infected alveolar macrophages. In a murine model of late-stage progressive MDR-TB, aerosolized delivery of SLMs containing OA and UA via a metered-dose inhaler significantly reduced pulmonary bacterial loads and extended survival. In vivo, acute toxicity studies revealed no mortality or signs of toxicity. These findings demonstrate that SLMs are an optimal delivery system for terpenoids, providing potent in vitro and in vivo anti-TB activity with an excellent safety profile. Full article
(This article belongs to the Special Issue Prevention, Treatment and Diagnosis of Tuberculosis, 2nd Edition)
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10 pages, 2199 KiB  
Communication
Comparison of Power Ultrasound and NALC-NaOH Decontamination Methods for Stool Mycobacterial Culture: A Prospective Study
by Peng Tian, Jing He, Xiaojie Ling, Yan Wang, Yunfeng Deng and Zhongfa Zhang
Microorganisms 2024, 12(9), 1799; https://doi.org/10.3390/microorganisms12091799 - 30 Aug 2024
Viewed by 713
Abstract
Stool samples have been reported to be useful for the diagnosis of pulmonary tuberculosis (PTB), especially in patients who are unable to produce sputum. However, contamination limits the usefulness of stool specimens in mycobacterial culture. In this study, a novel decontamination method of [...] Read more.
Stool samples have been reported to be useful for the diagnosis of pulmonary tuberculosis (PTB), especially in patients who are unable to produce sputum. However, contamination limits the usefulness of stool specimens in mycobacterial culture. In this study, a novel decontamination method of power ultrasound (PU) was evaluated for mycobacterial isolation from suspected PTB cases. Stool samples (n = 650) were collected, and each sample was divided into approximately three equal groups. In addition to an AFB smear (Auramine O method), the stool samples were treated using different decontamination methods (NaOH-NALC vs. PU methods). The sensitivity (calculated against CRS) and contamination rates between the two methods were compared using McNemar’s test. Of the 650 samples, 32 (4.92%) stool samples treated with the NaOH-NALC method were culture-positive, including Mycobacterium tuberculosis (M.TB; n = 21, 3.23%) and nontuberculous mycobacteria (NTM; n = 11, 1.69%). Sixty-one (9.38%) stool samples treated with the PU method were culture-positive, including M.TB (n = 37, 5.69%) and NTM (n = 24, 3.69%). Statistical analysis showed that a significant difference was found in the isolation rate of M.TB and NTM between the two methods (p < 0.05). Additionally, compared with the NALC-NaOH method (19.07%), stool samples treated with the PU method (13.23%) had a significantly lower contamination rate (p < 0.05). In conclusion, our findings suggest that the utilization of the PU method as a novel decontamination technique could significantly enhance the isolation rates of both NTM and M.TB when stool specimens are employed for culture. Compared to the NaOH-NALC method, this approach proves to be more effective in facilitating stool mycobacterial culture. Full article
(This article belongs to the Special Issue Prevention, Treatment and Diagnosis of Tuberculosis, 2nd Edition)
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18 pages, 1775 KiB  
Article
Adherence to Short-Duration Treatment (3HP) for Latent Tuberculosis among International Migrants in Manaus, Amazonas: Evaluation of the Efficacy of Different Treatment Modalities
by Yan Mathias Alves, Thaís Zamboni Berra, Sonia Vivian de Jezus, Vânia Maria Silva Araújo, Jair dos Santos Pinheiro, Lara Bezerra de Oliveira de Assis, Marvis Canelonez, Daniel Souza Sacramento, Freddy Perez, Ethel Leonor Noia Maciel and Ricardo Alexandre Arcêncio
Microorganisms 2024, 12(8), 1629; https://doi.org/10.3390/microorganisms12081629 - 9 Aug 2024
Viewed by 840
Abstract
Migration, a multifaceted phenomenon, has a significant impact on health. Migrants perform similar movement patterns within their country of origin, in transit, and in the country of destination, thus making it difficult to monitor TB treatment throughout the journey. The objective was to [...] Read more.
Migration, a multifaceted phenomenon, has a significant impact on health. Migrants perform similar movement patterns within their country of origin, in transit, and in the country of destination, thus making it difficult to monitor TB treatment throughout the journey. The objective was to compare the effectiveness of different treatment modalities in adherence to the short-term regimen for LTBI (3HP) among international migrants and refugees. This is a quasi-experimental study conducted in Manaus-AM. The study population was made up of international migrants. The certification and monitoring of medication intake employed three strategies: self-administration (SA), directly observed conventional therapy (DOT), and Video Telemonitoring System for Tuberculosis Treatment (VDOT). The VDOT group and SA group exhibited the lowest rate of treatment dropout or interruption at 16.1%, followed by the DOT group at 23.1%. The results suggest that the most effective strategy for ensuring adherence among migrants and refugees was VDOT (OR_adj 0.26; CI 0.7–0.94), suggesting that migrants may be more likely to adhere to and complete their treatment. The results show that relying on different treatment strategies, adapted to the individuals’ needs and risk factors, is a viable and effective way of providing person-centered TB care. Full article
(This article belongs to the Special Issue Prevention, Treatment and Diagnosis of Tuberculosis, 2nd Edition)
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14 pages, 5294 KiB  
Article
Antimicrobial Effect of Chitosan Nanoparticles and Allium Species on Mycobacterium tuberculosis and Several Other Microorganisms
by Jocelyn Olivas-Flores, José Román Chávez-Méndez, Nydia Alejandra Castillo-Martínez, Héctor Javier Sánchez-Pérez, Aracely Serrano-Medina and José Manuel Cornejo-Bravo
Microorganisms 2024, 12(8), 1605; https://doi.org/10.3390/microorganisms12081605 - 6 Aug 2024
Viewed by 1111
Abstract
This study evaluates the antimicrobial efficacy of chitosan nanoparticles (CNPs), varying in size, against clinical isolates of Mycobacterium tuberculosis (MTB), E. coli, S. aureus, E. faecalis, and C. albicans, as well as the antimicrobial effects of aqueous extracts and [...] Read more.
This study evaluates the antimicrobial efficacy of chitosan nanoparticles (CNPs), varying in size, against clinical isolates of Mycobacterium tuberculosis (MTB), E. coli, S. aureus, E. faecalis, and C. albicans, as well as the antimicrobial effects of aqueous extracts and lyophilized powders of Allium (garlic) species. CNPs were synthesized through ionotropic gelation and characterized by Z potential, hydrodynamic diameter (dynamic light scattering, DLS), and SEM. Aqueous garlic extracts were prepared via decoction. We assessed antimicrobial activity using disk diffusion and broth microdilution methods; in addition, a modified agar proportion method in blood agar was used for antimicrobial activity against MTB. CNPs inhibited MTB growth at 300 μg for 116.6 nm particles and 400 μg for 364.4 nm particles. The highest antimicrobial activity was observed against E. faecalis with nanoparticles between 200 and 280 nm. Allium sativum extract produced inhibition for C. albicans at 100 μg. The results indicate that CNPs possess significant antimicrobial properties against a range of pathogens, including MTB, at high concentrations. On the other hand, aqueous Allium sativum extracts exhibited antimicrobial activity. Nonetheless, due to their instability in solution, the use of lyophilized Allium sativum powder is preferable. Full article
(This article belongs to the Special Issue Prevention, Treatment and Diagnosis of Tuberculosis, 2nd Edition)
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13 pages, 2720 KiB  
Article
The Repurposing of FDA-Approved Drugs as FtsZ Inhibitors against Mycobacterium tuberculosis: An In Silico and In Vitro Study
by Andrea Michel Tovar-Nieto, Luis Enrique Flores-Padilla, Bruno Rivas-Santiago, Juan Valentin Trujillo-Paez, Edgar Eduardo Lara-Ramirez, Yolanda M. Jacobo-Delgado, Juan Ernesto López-Ramos and Adrián Rodríguez-Carlos
Microorganisms 2024, 12(8), 1505; https://doi.org/10.3390/microorganisms12081505 - 23 Jul 2024
Viewed by 1138
Abstract
Mycobacterium tuberculosis (Mtb), the causative pathogen of tuberculosis, remains one of the leading causes of death from a single infectious agent. Furthermore, the growing evolution to multi-drug-resistant (MDR) strains requires de novo identification of drug targets for evaluating candidates or repurposing drugs. Hence, [...] Read more.
Mycobacterium tuberculosis (Mtb), the causative pathogen of tuberculosis, remains one of the leading causes of death from a single infectious agent. Furthermore, the growing evolution to multi-drug-resistant (MDR) strains requires de novo identification of drug targets for evaluating candidates or repurposing drugs. Hence, targeting FtsZ, an essential cell division protein, is a promising target. Methods: Using an in silico pharmacological repositioning strategy, four FDA-based drugs that bind to the catalytic site FtsZ were selected. The Alamar Blue colorimetric assay was used to assess antimicrobial activity and the effect of drugs on Mtb growth through growth curves. Bacterial load was determined with an in vitro infection model using colony-forming units (CFU)/mL, and cytotoxicity on human monocyte-derived macrophages (MDMhs) was assessed by flow cytometry. Results: Paroxetine and nebivolol exhibited antimycobacterial activity against both reference TB and MDR strains at a concentration of 25 µg/mL. Furthermore, both paroxetine and nebivolol demonstrated a significant reduction (p < 0.05) in viable bacteria compared to the untreated group in the in vitro infection model. Conclusions: Collectively, our findings demonstrate that the use of paroxetine and nebivolol is a promising strategy to help in the control of tuberculosis infection. Full article
(This article belongs to the Special Issue Prevention, Treatment and Diagnosis of Tuberculosis, 2nd Edition)
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14 pages, 5397 KiB  
Article
Exosomal Small RNA Sequencing Profiles in Plasma from Subjects with Latent Mycobacterium tuberculosis Infection
by Xiaogang Cui, Hangting Meng, Miao Li, Xia Chen, Dan Yuan and Changxin Wu
Microorganisms 2024, 12(7), 1417; https://doi.org/10.3390/microorganisms12071417 - 12 Jul 2024
Viewed by 998
Abstract
Despite huge efforts, tuberculosis (TB) is still a major public health threat worldwide, with approximately 23% of the human population harboring a latent TB infection (LTBI). LTBI can reactivate and progress to active and transmissible TB disease, contributing to its spread within the [...] Read more.
Despite huge efforts, tuberculosis (TB) is still a major public health threat worldwide, with approximately 23% of the human population harboring a latent TB infection (LTBI). LTBI can reactivate and progress to active and transmissible TB disease, contributing to its spread within the population. The challenges in diagnosing and treating LTBI patients have been major factors contributing to this phenomenon. Exosomes offer a novel avenue for investigating the process of TB infection. In this study, we conducted small RNA sequencing to investigate the small RNA profiles of plasma exosomes derived from individuals with LTBI and healthy controls. Our findings revealed distinct miRNA profiles in the exosomes between the two groups. We identified 12 differentially expressed miRNAs through this analysis, which were further validated via qRT-PCR using the same exosomes. Notably, six miRNAs (hsa-miR-7850-5p, hsa-miR-1306-5p, hsa-miR-363-5p, hsa-miR-374a-5p, hsa-miR-4654, has-miR-6529-5p, and hsa-miR-140-5p) exhibited specifically elevated expression in individuals with LTBI. Gene ontology and KEGG pathway analyses revealed that the targets of these miRNAs were enriched in functions associated with ferroptosis and fatty acid metabolism, underscoring the critical role of these miRNAs in regulating the intracellular survival of Mycobacterium tuberculosis (Mtb). Furthermore, our results indicated that the overexpression of miR-7850-5p downregulated the expression of the SLC11A1 protein in both Mtb-infected and Mtb-uninfected THP1 cells. Additionally, we observed that miR-7850-5p promoted the intracellular survival of Mtb by suppressing the expression of the SLC11A1 protein. Overall, our findings provide valuable insights into the role of miRNAs and repetitive region-derived small RNAs in exosomes during the infectious process of Mtb and contribute to the identification of potential molecular targets for the detection and diagnosis of latent tuberculosis. Full article
(This article belongs to the Special Issue Prevention, Treatment and Diagnosis of Tuberculosis, 2nd Edition)
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