Mycobacterial Tuberculosis Pathogenesis and Vaccine Development

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

Deadline for manuscript submissions: 30 June 2024 | Viewed by 6233

Special Issue Editors


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Guest Editor
Department of Pathobiological Sciences, School of Veterinary Medicine, University of Wisconsin, Madison, WI 53706, USA
Interests: nanoparticle-based vaccine development

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Guest Editor
Johns Hopkins School of Medicine, Baltimore, MD, USA
Interests: vaccines; immunotherapy; immunopathology; experimental modeling; tuberculosis; infectious diseases
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

It is time to renew our understanding of tuberculosis pathogenesis and the development of immunity. With recent development in the fields of genomics, system biology and chemical synthesis, new frontiers for studying infectious diseases and their impact on host health have increased tremendously. Already, strong gains have been in the field of tuberculosis. In this this Special Issue, we welcome your contributions (original research articles, opinions, short articles, reviews) from studying various species of Mycobacterium causing diseases to both animals and humans. Research areas may include (but are not limited to) the following areas: mycobacterial pathogenesis, immunity, genomics, epidemiology, therapy and vaccine development.

I/We look forward to receiving your contributions.

Prof. Dr. Adel M. Talaat
Prof. Dr. Petros C. Karakousis
Guest Editors

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Keywords

  • tuberculosis
  • pathogenesis
  • vaccine
  • immunity
  • epidemiology
  • therapy

Published Papers (5 papers)

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Research

12 pages, 1016 KiB  
Article
Transcriptional Profiling of Homologous Recombination Pathway Genes in Mycobacterium bovis BCG Moreau
by Marcos Gustavo Araujo Schwarz, Paloma Rezende Corrêa and Leila Mendonça-Lima
Microorganisms 2023, 11(10), 2534; https://doi.org/10.3390/microorganisms11102534 - 11 Oct 2023
Viewed by 786
Abstract
Mycobacterium bovis BCG Moreau is the main Brazilian strain for vaccination against tuberculosis. It is considered an early strain, more like the original BCG, whereas BCG Pasteur, largely used as a reference, belongs to the late strain clade. BCG Moreau, contrary to Pasteur, [...] Read more.
Mycobacterium bovis BCG Moreau is the main Brazilian strain for vaccination against tuberculosis. It is considered an early strain, more like the original BCG, whereas BCG Pasteur, largely used as a reference, belongs to the late strain clade. BCG Moreau, contrary to Pasteur, is naturally deficient in homologous recombination (HR). In this work, using a UV exposure test, we aimed to detect differences in the survival of various BCG strains after DNA damage. Transcription of core and regulatory HR genes was further analyzed using RT-qPCR, aiming to identify the molecular agent responsible for this phenotype. We show that early strains share the Moreau low survival rate after UV exposure, whereas late strains mimic the Pasteur phenotype, indicating that this increase in HR efficiency is linked to the evolutionary clade history. Additionally, RT-qPCR shows that BCG Moreau has an overall lower level of these transcripts than Pasteur, indicating a correlation between this gene expression profile and HR efficiency. Further assays should be performed to fully identify the molecular mechanism that may explain this differential phenotype between early and late BCG strains. Full article
(This article belongs to the Special Issue Mycobacterial Tuberculosis Pathogenesis and Vaccine Development)
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12 pages, 802 KiB  
Article
Vaccination of White-Tailed Deer with Mycobacterium bovis Bacillus Calmette–Guérin (BCG): Effect of Mycobacterium avium ssp. paratuberculosis Infection
by Mitchell V. Palmer, Carly Kanipe, Kimberly A. Lehman, Tyler C. Thacker, Ellie J. Putz and Paola M. Boggiatto
Microorganisms 2023, 11(10), 2488; https://doi.org/10.3390/microorganisms11102488 - 04 Oct 2023
Viewed by 1026
Abstract
In many parts of the world, bovine tuberculosis eradication efforts are hampered by wildlife reservoirs of Mycobacterium bovis, which serve as a constant source of M. bovis for nearby cattle. The human tuberculosis vaccine, M. bovis BCG has been investigated for use [...] Read more.
In many parts of the world, bovine tuberculosis eradication efforts are hampered by wildlife reservoirs of Mycobacterium bovis, which serve as a constant source of M. bovis for nearby cattle. The human tuberculosis vaccine, M. bovis BCG has been investigated for use in several wildlife species, including deer. In the US, white-tailed deer in Michigan have been the source of infection for over 82 cattle herds since M. bovis was discovered in free-ranging deer in 1995. The efficacy of BCG may be influenced by many factors, including prior exposure or infection with non-tuberculous mycobacteria, that is, species other than members of the M. tuberculosis complex. M. avium subspecies paratuberculosis (Map) infection is not uncommon in ruminants such as deer. Using natural exposure to Map and experimental infection with M. bovis, we demonstrate that Map infection increased BCG vaccine efficacy as measured by lesion severity scores. Full article
(This article belongs to the Special Issue Mycobacterial Tuberculosis Pathogenesis and Vaccine Development)
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15 pages, 1344 KiB  
Article
Functional Whole Genome Screen of Nutrient-Starved Mycobacterium tuberculosis Identifies Genes Involved in Rifampin Tolerance
by William M. Matern, Harley T. Harris, Carina Danchik, Marissa McDonald, Gopi Patel, Aashish Srivastava, Thomas R. Ioerger, Joel S. Bader and Petros C. Karakousis
Microorganisms 2023, 11(9), 2269; https://doi.org/10.3390/microorganisms11092269 - 09 Sep 2023
Viewed by 1256
Abstract
Mycobacterium tuberculosis (Mtb), the causative agent of tuberculosis (TB), poses a global health challenge and is responsible for over a million deaths each year. Current treatment is lengthy and complex, and new, abbreviated regimens are urgently needed. Mtb adapts to nutrient [...] Read more.
Mycobacterium tuberculosis (Mtb), the causative agent of tuberculosis (TB), poses a global health challenge and is responsible for over a million deaths each year. Current treatment is lengthy and complex, and new, abbreviated regimens are urgently needed. Mtb adapts to nutrient starvation, a condition experienced during host infection, by shifting its metabolism and becoming tolerant to the killing activity of bactericidal antibiotics. An improved understanding of the mechanisms mediating antibiotic tolerance in Mtb can serve as the basis for developing more effective therapies. We performed a forward genetic screen to identify candidate Mtb genes involved in tolerance to the two key first-line antibiotics, rifampin and isoniazid, under nutrient-rich and nutrient-starved conditions. In nutrient-rich conditions, we found 220 mutants with differential antibiotic susceptibility (218 in the rifampin screen and 2 in the isoniazid screen). Following Mtb adaptation to nutrient starvation, 82 mutants showed differential antibiotic susceptibility (80 in the rifampin screen and 2 in the isoniazid screen). Using targeted mutagenesis, we validated the rifampin-hypersusceptible phenotype under nutrient starvation in Mtb mutants lacking the following genes: ercc3, moeA1, rv0049, and rv2179c. These findings shed light on potential therapeutic targets, which could help shorten the duration and complexity of antitubercular regimens. Full article
(This article belongs to the Special Issue Mycobacterial Tuberculosis Pathogenesis and Vaccine Development)
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15 pages, 5430 KiB  
Article
The Immunogenicity and Safety of Mycobacterium tuberculosis-mosR-Based Double Deletion Strain in Mice
by Rachel E. Hildebrand, Chungyi Hansen, Brock Kingstad-Bakke, Chia-Wei Wu, Marulasiddappa Suresh and Adel Talaat
Microorganisms 2023, 11(8), 2105; https://doi.org/10.3390/microorganisms11082105 - 18 Aug 2023
Viewed by 1379
Abstract
Mycobacterium tuberculosis (M. tuberculosis) remains a significant global health threat, accounting for ~1.7 million deaths annually. The efficacy of the current vaccine, M. bovis BCG, ranges from 0 to 80% in children and does not prevent adulthood tuberculosis. We explored the [...] Read more.
Mycobacterium tuberculosis (M. tuberculosis) remains a significant global health threat, accounting for ~1.7 million deaths annually. The efficacy of the current vaccine, M. bovis BCG, ranges from 0 to 80% in children and does not prevent adulthood tuberculosis. We explored the immune profile and safety of a live-attenuated M. tuberculosis construct with double deletions of the mosR and echA7 genes, where previously, single mutations were protective against an M. tuberculosis aerosol challenge. Over 32 weeks post-vaccination (WPV), immunized mice with M. tuberculosisΔmosRΔechA7 (double mutant) were sacrificed to evaluate the vaccine persistence, histopathology, and immune responses. Interestingly, despite similar tissue colonization between the vaccine double mutant and wild-type M. tuberculosis, the vaccine construct showed a greater reaction to the ESAT-6, TB.10, and Ag85B antigens with peptide stimulation. Additionally, there was a greater number of antigen-specific CD4 T cells in the vaccine group, accompanied by significant polyfunctional T-cell responses not observed in the other groups. Histologically, mild but widely distributed inflammatory responses were recorded in the livers and lungs of the immunized animals at early timepoints, which turned into organized inflammatory foci via 32WPV, a pathology not observed in BCG-immunized mice. A lower double-mutant dose resulted in significantly less tissue colonization and less tissue inflammation. Overall, the double-mutant vaccine elicited robust immune responses dominated by antigen-specific CD4 T cells, but also triggered tissue damage and vaccine persistence. The findings highlight key features associated with the immunogenicity and safety of the examined vaccine construct that can benefit the future evaluation of other live vaccines. Full article
(This article belongs to the Special Issue Mycobacterial Tuberculosis Pathogenesis and Vaccine Development)
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18 pages, 2356 KiB  
Article
Association between High Interferon-Gamma Production in Avian Tuberculin-Stimulated Blood from Mycobacterium avium subsp. paratuberculosis-Infected Cattle and Candidate Genes Implicated in Necroptosis
by Gerard Badia-Bringué, María Canive, Patricia Vázquez, Joseba M. Garrido, Almudena Fernández, Ramón A. Juste, José Antonio Jiménez, Oscar González-Recio and Marta Alonso-Hearn
Microorganisms 2023, 11(7), 1817; https://doi.org/10.3390/microorganisms11071817 - 15 Jul 2023
Cited by 1 | Viewed by 1114
Abstract
The mechanisms underlying host resistance to Mycobacterium avium subsp. paratuberculosis (MAP) infection are largely unknown. In the current study, we hypothesize that cows with an ability to produce higher levels of interferon-gamma (IFNɣ) might control MAP infection more successfully. To test this hypothesis, [...] Read more.
The mechanisms underlying host resistance to Mycobacterium avium subsp. paratuberculosis (MAP) infection are largely unknown. In the current study, we hypothesize that cows with an ability to produce higher levels of interferon-gamma (IFNɣ) might control MAP infection more successfully. To test this hypothesis, IFNɣ production was measured using a specific IFNɣ ELISA kit in avian purified protein derivative (aPPD)-stimulated blood samples collected from 152 Holstein cattle. DNA isolated from peripheral blood samples of the animals included in the study was genotyped with the EuroG Medium-Density Bead Chip, and the genotypes were imputed to whole-genome sequencing. A genome-wide association analysis (GWAS) revealed that high levels of IFNɣ in response to the aPPD were associated with a specific genetic profile (heritability = 0.64) and allowed the identification of 71 SNPs, 40 quantitative trait loci (QTL), and 104 candidate genes. A functional analysis using the 104 candidate genes revealed a significant enrichment of genes involved in the innate immune response and, more specifically, in necroptosis. Taken together, our results define a heritable and distinct immunogenetic profile associated with the production of high IFNɣ levels and with the capacity of the host to lyse MAP-infected macrophages by necroptosis. Full article
(This article belongs to the Special Issue Mycobacterial Tuberculosis Pathogenesis and Vaccine Development)
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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.

Immunogenicity and safety of Mycobacterium tuberculosis-mosR-based double deletion strain in Mice”, but it might change when we are ready for submission
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