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Frontiers in Cellular and Infection... 2024The causative agent of tuberculosis in pinnipeds is , a member of the complex (MTC). The natural hosts are pinnipeds; however, other non-marine mammals, including...
The causative agent of tuberculosis in pinnipeds is , a member of the complex (MTC). The natural hosts are pinnipeds; however, other non-marine mammals, including humans, can also be infected. The transmissibility of a pathogen is related to its virulence. The transmissibility of a strain (i.e., 1856) was investigated in a murine model and compared with that of two strains (i.e., 534 and 04-303) with different reported virulence. Non-inoculated mice (sentinels) were co-housed with intratracheally inoculated mice. Detailed inspection of mice to search for visible tuberculosis lesions in the lungs and spleen was performed, and bacillus viability at 30, 60, and 90 days post-inoculation (dpi) was assayed. A transmissibility of 100% was recorded at 30 dpi in sentinel mice co-housed with the inoculated mice from the and 04-303 groups, as evidenced by the recovery of viable and from the lungs of sentinel mice. Mice inoculated with (1856) and (534) survived until euthanized, whereas five of the 04-303-inoculated mice died at 17 dpi. This study constitutes the first report of the transmissibility of a strain in mice and confirms the utility of this experimental model to study virulence features such as the transmission of poorly characterized MTC species.
Topics: Humans; Animals; Mice; Disease Models, Animal; Tuberculosis; Mycobacterium bovis; Caniformia; Spleen; Mycobacterium tuberculosis
PubMed: 38606297
DOI: 10.3389/fcimb.2024.1328981 -
Veterinary Journal (London, England :... Jun 2024Canine mycobacterial disease was first recognised over 100 years ago but is now an emerging concern. All reported cases of tuberculous disease in dogs have been caused... (Review)
Review
Canine mycobacterial disease was first recognised over 100 years ago but is now an emerging concern. All reported cases of tuberculous disease in dogs have been caused by infection with one of three Mycobacterium tuberculosis-complex (MTBC) organisms (M. tuberculosis, Mycobacterium bovis, and Mycobacterium microti). Molecular PCR and interferon-gamma release assays offer alternative or complementary diagnostic pathways to that of specialist culture, which is limited by availability, sensitivity, and the time it takes to get a result. Optimised triple antimicrobial protocols offer an excellent chance of a successful outcome in dogs where treatment can be considered and is attempted. In this review, the clinical presentation, diagnosis, treatment, and prognosis of canine tuberculosis are discussed.
Topics: Dogs; Dog Diseases; Animals; Tuberculosis; Antitubercular Agents; Mycobacterium tuberculosis
PubMed: 38604331
DOI: 10.1016/j.tvjl.2024.106111 -
Preventive Veterinary Medicine Jun 2024Tuberculosis (TB) is a zoonotic infectious disease caused by bacteria belonging to the Mycobacterium tuberculosis complex (MTC), which can affect a wide variety of...
Tuberculosis (TB) is a zoonotic infectious disease caused by bacteria belonging to the Mycobacterium tuberculosis complex (MTC), which can affect a wide variety of domestic and wild animal species. Although the role of goats as a reservoir of MTC bacteria has been evidenced, information about the circulation of MTC strains in this species is still very scarce. The aim of the present study was to determine the seroprevalence, spatial distribution, risk factors and MTC spoligotypes circulating in goats from Andalusia (Southern Spain), the Spanish region with the largest goat census and a hotspot area of TB in both cattle and wild ungulates. A total of 2155 serum samples from 80 goat flocks were analyzed by an in-house ELISA using the P22 protein complex as a coating antigen. Antibodies against MTC were detected in 473 goats (21.9%, 95% CI: 20.2-23.7) and the true seroprevalence was 22.3% (95% CI: 20.6-24.1). Seropositivity was found in 72 (90.0%) of the 80 flocks analyzed. The generalized estimating equation model showed that the management system (higher seroprevalence on intensive and semi-intensive farms), and the presence of hospital pens inside the regular stables, were risk factors potentially associated with MTC exposure in goats in Southern Spain. The spatial analysis identified a significant spatial cluster (p < 0.001) in Eastern Andalusia. A total of 16 different MTC spoligotypes, including five of M. caprae and eleven of M. bovis, were identified in goats between 2015 and 2022 in the study area, with SB0157 as the most frequently isolated. The results obtained indicate widespread and non-homogeneous spatial distribution of MTC in goat herds from Southern Spain. The high individual and herd-level seroprevalence values found suggest that goats could play a significant role in the maintenance and transmission of MTC in the study area. Our results highlight the importance of implementing control measures in this species.
Topics: Animals; Goats; Spain; Goat Diseases; Seroepidemiologic Studies; Tuberculosis; Mycobacterium tuberculosis; Risk Factors; Female; Enzyme-Linked Immunosorbent Assay; Male; Prevalence
PubMed: 38604014
DOI: 10.1016/j.prevetmed.2024.106204 -
Journal of Clinical Tuberculosis and... May 2024Antimicrobial resistance alongside other challenges in tuberculosis (TB) therapeutics have stirred renewed interest in host-directed interventions, including the role of...
Antimicrobial resistance alongside other challenges in tuberculosis (TB) therapeutics have stirred renewed interest in host-directed interventions, including the role of antibodies as adjunct therapeutic agents. This study assessed the binding efficacy of two novel IgG1 opsonic monoclonal antibodies (MABs; GG9 & JG7) at 5, 10, and 25 µg/mL to live cultures of , , , , and American Type Culture Collection laboratory reference strains, as well as clinical susceptible, multi-drug resistant, and extensively drug resistant strains using indirect enzyme-linked immunosorbent assays. These three MAB concentrations were selected from a range of concentrations used in previous optimization (binding and functional) assays. Both MABs bound to all mycobacterial species and sub-types tested, albeit to varying degrees. Statistically significant differences in MAB binding activity were observed when comparing the highest and lowest MAB concentrations (p < 0.05) for both MABs GG9 and JG7, irrespective of the resistance profile. Binding affinity increased with an increase in MAB concentration, and optimal binding was observed at 25 µg/mL. JG7 showed better binding activity than GG9. Both MABs also bound to five MOTT species, albeit at varied levels. This non-selective binding to different mycobacterial species suggests a potential role for GG9 and JG7 as adjunctive agents in anti-TB chemotherapy with the aim to enhance bacterial killing.
PubMed: 38601919
DOI: 10.1016/j.jctube.2024.100435 -
Cancer Pathogenesis and Therapy Apr 2024Bladder cancer encapsulates a wide spectrum of disease severities, with non-muscle invasive bladder cancer (NMIBC) representing an entirely different entity from... (Review)
Review
Bladder cancer encapsulates a wide spectrum of disease severities, with non-muscle invasive bladder cancer (NMIBC) representing an entirely different entity from muscle-invasive disease. Bacillus Calmette-Guérin (BCG) is one of the most successful intravesical treatment methods for patients diagnosed. However, a considerable proportion of patients fail to respond to BCG treatment. Given the propensity for recurrence in patients with high-risk bladder cancer, these patients present with surgical dilemmas. There is currently no gold standard for salvage treatment post-BCG failure or unified definition as to what that means. In this review, we discuss the mechanisms of action and pathophysiology of BCG, potential theories behind BCG failure, and the scope of novel treatments for this surgical conundrum.
PubMed: 38601486
DOI: 10.1016/j.cpt.2023.11.004 -
Atypical ulcerative cutaneous tuberculosis in a zosteriform distribution due to Mycobacterium bovis.Indian Journal of Dermatology,... Mar 2024
PubMed: 38594992
DOI: 10.25259/IJDVL_370_2023 -
Frontiers in Immunology 2024There is currently no vaccine against Chagas disease (ChD), and the medications available confer multiple side effects. Bacillus Calmette-Guérin (BCG) produces...
INTRODUCTION
There is currently no vaccine against Chagas disease (ChD), and the medications available confer multiple side effects. Bacillus Calmette-Guérin (BCG) produces balanced Th1, Th2, and Th17 modulatory immune responses and has improved efficacy in controlling chronic infections through nonspecific immunity. We aimed to improve the response to infection by inducing a stronger immune response and greater protection against the parasite by trained immunity.
METHODS
BALB/c mice were immunized with BCG subcutaneously, and 60 days later, they were infected with intraperitoneally. An evaluation of the progression of the disease from the acute to the chronic stage, analyzing various aspects such as parasitemia, survival, clinical status, and humoral and cellular immune response, as well as the appearance of visceral megas and the histopathological description of target organs, was performed.
RESULTS
Vaccination reduced parasitemia by 70%, and 100% survival was achieved in the acute stage; although the presentation of clinical signs was reduced, there was no increase in the antibody titer or in the differential production of the isotypes.
CONCLUSION
Serum cytokine production indicated a proinflammatory response in infected animals, while in those who received BCG, the response was balanced by inducing Th1/Th2-type cytokines, with a better prognosis of the disease in the chronic stage.
Topics: Animals; Mice; Mycobacterium bovis; BCG Vaccine; Parasitemia; Persistent Infection; Chagas Disease; Adjuvants, Immunologic
PubMed: 38576607
DOI: 10.3389/fimmu.2024.1380049 -
Journal of Cancer Prevention Mar 2024Bacillus Calmette-Guérin (BCG) is an attenuated strain of . Although it was developed as a prophylactic vaccine against tuberculosis (TB), researchers have also... (Review)
Review
Bacillus Calmette-Guérin (BCG) is an attenuated strain of . Although it was developed as a prophylactic vaccine against tuberculosis (TB), researchers have also evaluated it for preventing cancer development or progression. These studies were inspired by the available data regarding the protective effects of microbial infection against cancers and an inverse relationship between TB and cancer mortality. Initial studies demonstrated the efficacy of BCG in preventing leukemia, melanoma and a few other cancers. However, mixed results were observed in later studies. Importantly, these studies have led to the successful use of BCG in the tertiary prevention of non-muscle invasive bladder cancer, wherein BCG therapy has been found to be more effective than chemotherapy. Moreover, in a recently published 60-year follow-up study, childhood BCG vaccination has been found to significantly prevent lung cancer development. In the present manuscript, we reviewed the studies evaluating the efficacy of BCG in cancer prevention and discussed its putative mechanisms. Also, we sought to explain the mixed results of BCG efficacy in preventing different cancers.
PubMed: 38567111
DOI: 10.15430/JCP.23.036 -
BioRxiv : the Preprint Server For... Jun 2024Mycobacterium bovis BCG is the vaccine against tuberculosis and an immunotherapy for bladder cancer. When administered intravenously, BCG reprograms bone marrow...
Mycobacterium bovis BCG is the vaccine against tuberculosis and an immunotherapy for bladder cancer. When administered intravenously, BCG reprograms bone marrow hematopoietic stem and progenitor cells (HSPCs), leading to heterologous protection against infections. Whether HSPC-reprogramming contributes to the anti-tumor effects of BCG administered into the bladder is unknown. We demonstrate that BCG administered in the bladder in both mice and humans reprograms HSPCs to amplify myelopoiesis and functionally enhance myeloid cell antigen presentation pathways. Reconstitution of naive mice with HSPCs from bladder BCG-treated mice enhances anti-tumor immunity and tumor control, increases intratumor dendritic cell infiltration, reprograms pro-tumorigenic neutrophils, and synergizes with checkpoint blockade. We conclude that bladder BCG acts systemically, reprogramming HSPC-encoded innate immunity, highlighting the broad potential of modulating HSPC phenotypes to improve tumor immunity.
PubMed: 38562703
DOI: 10.1101/2024.03.21.586166 -
Tuberculosis (Edinburgh, Scotland) Jul 2024Tuberculosis, caused by Mycobacterium tuberculosis, remains one of the deadliest infections in humans. Because Mycobacterium bovis Bacillus Calmette-Guérin (BCG) share...
Tuberculosis, caused by Mycobacterium tuberculosis, remains one of the deadliest infections in humans. Because Mycobacterium bovis Bacillus Calmette-Guérin (BCG) share genetic similarities with Mycobacterium tuberculosis, it is often used as a model to elucidate the molecular mechanisms of more severe tuberculosis infection. Caveolin-1 has been implied in many physiological processes and diseases, but it's role in mycobacterial infections has barely been studied. We isolated macrophages from Wildtype or Caveolin-1 deficient mice and analyzed hallmarks of infection, such as internalization, induction of autophagy and apoptosis. For in vivo assays we intravenously injected mice with BCG and investigated tissues for bacterial load with colony-forming unit assays, bioactive lipids with mass spectrometry and changes of protein expressions by Western blotting. Our results revealed that Caveolin-1 was important for early killing of BCG infection in vivo and in vitro, controlled acid sphingomyelinase (Asm)-dependent ceramide formation, apoptosis and inflammatory cytokines upon infection with BCG. In accordance, Caveolin-1 deficient mice and macrophages showed higher bacterial burdens in the livers. The findings indicate that Caveolin-1 plays a role in infection of mice and murine macrophages with BCG, by controlling cellular apoptosis and inflammatory host response. These clues might be useful in the fight against tuberculosis.
Topics: Animals; Caveolin 1; Apoptosis; Mycobacterium bovis; Mice, Knockout; Mice, Inbred C57BL; Macrophages; Tuberculosis; Sphingomyelin Phosphodiesterase; Autophagy; Host-Pathogen Interactions; Disease Models, Animal; Bacterial Load; Cytokines; Ceramides; Liver; Cells, Cultured; Mice; Inflammation Mediators; Time Factors
PubMed: 38547568
DOI: 10.1016/j.tube.2024.102493