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ACS Omega Oct 2023The aim of this study was to evaluate the potential antibiofilm activity of () compounds over BCG ( BCG) as a model for (). We evaluated the antibiofilm activity as...
The aim of this study was to evaluate the potential antibiofilm activity of () compounds over BCG ( BCG) as a model for (). We evaluated the antibiofilm activity as the ability to both inhibit biofilm formation and disrupt preformed biofilms (bactericidal) of compounds, which have been previously described as being antimycobacterials against . BCG developed air-liquid interface biofilms with surface attachment ability and drug tolerance. Of the extracts and compounds that were tested, precatorin A (PreA) displayed the best biofilm inhibitory activity, as evaluated by biofilm biomass quantification, viable cell count, and confocal and atomic force microscopy procedures. Furthermore, its combination with isoniazid at subinhibitory concentrations inhibited BCG biofilm formation. Nonetheless, neither PreA nor the extract showed bactericidal effects. PreA is the compound responsible for biofilm inhibitory activity against BCG.
PubMed: 37929145
DOI: 10.1021/acsomega.3c05703 -
Pathogens (Basel, Switzerland) Nov 2023The bacillus Calmette-Guérin (BCG) is an attenuated bacterium derived from virulent . It is the only licensed vaccine used for preventing severe forms of tuberculosis... (Review)
Review
The bacillus Calmette-Guérin (BCG) is an attenuated bacterium derived from virulent . It is the only licensed vaccine used for preventing severe forms of tuberculosis in children. Besides its specific effects against tuberculosis, BCG administration is also associated with beneficial non-specific effects (NSEs) following heterologous stimuli in humans and mice. The NSEs from BCG could be related to both adaptive and innate immune responses. The latter is also known as trained immunity (TI), a recently described biological feature of innate cells that enables functional improvement based on metabolic and epigenetic reprogramming. Currently, the mechanisms related to BCG-mediated TI are the focus of intense research, but many gaps are still in need of elucidation. This review discusses the present understanding of TI induced by BCG, exploring signaling pathways that are crucial to a trained phenotype in hematopoietic stem cells and monocytes/macrophages lineage. It focuses on BCG-mediated TI mechanisms, including the metabolic-epigenetic axis and the inflammasome pathway in these cells against intracellular pathogens. Moreover, this study explores the TI in different immune cell types, its ability to protect against various intracellular infections, and the integration of trained innate memory with adaptive memory to shape next-generation vaccines.
PubMed: 38133271
DOI: 10.3390/pathogens12121386 -
Microbiology Spectrum May 2024causes animal tuberculosis in livestock and wildlife, with an impact on animal health and production, wildlife management, and public health. In this work, we sampled a...
UNLABELLED
causes animal tuberculosis in livestock and wildlife, with an impact on animal health and production, wildlife management, and public health. In this work, we sampled a multi-host tuberculosis community from the official hotspot risk area of Portugal over 16 years, generating the largest available data set in the country. Using phylogenetic and ecological modeling, we aimed to reconstruct the history of circulating lineages across the livestock-wildlife interface to inform intervention and the implementation of genomic surveillance within the official eradication plan. We find evidence for the co-circulation of European 1 (Eu1), Eu2, and Eu3 clonal complexes, with Eu3 providing sufficient temporal signal for further phylogenetic investigation. The Eu3 most recent common ancestor (bovine) was dated in the 1990s, subsequently transitioning to wildlife (red deer and wild boar). Isolate clustering based on sample metadata was used to inform phylogenetic inference, unravelng frequent transmission between two clusters that represent an ecological corridor of previously unrecognized importance in Portugal. The latter was associated with transmission at the livestock-wildlife interface toward locations with higher temperature and precipitation, lower agriculture and road density, and lower host densities. This is the first analysis of Eu3 complex in Iberia, shedding light on background ecological factors underlying long-term transmission and informing where efforts could be focused within the larger hotspot risk area of Portugal.
IMPORTANCE
Efforts to strengthen surveillance and control of animal tuberculosis (TB) are ongoing worlwide. Here, we developed an eco-phylodynamic framework based on discrete phylogenetic approaches informed by whole-genome sequence data representing a multi-host transmission system at the livestock-wildlife interface, within a rich ecological landscape in Portugal, to understand transmission processes and translate this knowledge into disease management benefits. We find evidence for the co-circulation of several clades, with frequent transmission of the Eu3 lineage among cattle and wildlife populations. Most transition events between different ecological settings took place toward host, climate and land use gradients, underscoring animal TB expansion and a potential corridor of unrecognized importance for maintenance. Results stress that animal TB is an established wildlife disease without ecological barriers, showing that control measures in place are insufficient to prevent long-distance transmission and spillover across multi-host communities, demanding new interventions targeting livestock-wildlife interactions.
PubMed: 38771094
DOI: 10.1128/spectrum.03829-23 -
Human Vaccines & Immunotherapeutics Dec 2024Tuberculosis (TB), caused by the intracellular pathogen (), affects the lungs of infected individuals (pulmonary TB) but can also affect other sites (extrapulmonary...
Tuberculosis (TB), caused by the intracellular pathogen (), affects the lungs of infected individuals (pulmonary TB) but can also affect other sites (extrapulmonary TB). The only licensed vaccine bacillus (BCG) protects infants and young children but exhibits variable efficacy in protecting against adult pulmonary TB. Poor compliance and prolonged treatment regimens associated with the use of chemotherapy has contributed to the development of multidrug-resistant (MDR) and extensively drug-resistant (XDR) . Thus, there is an urgent need for the design of more effective vaccines against TB. The development of safe and novel adjuvants for human use is critical. In this study, we demonstrate that saponin-based TQL1055 adjuvant when formulated with a TLR4 agonist (PHAD) and specific immunodominant antigens (ESAT-6 and Ag85B) and delivered intramuscularly in mice, the SA-TB vaccine induced potent lung immune responses. Additionally, the SA-TB vaccine conferred significant protection against infection, comparable with levels induced by BCG. These findings support the development of a SA-TB vaccine comprising TQL1055, as a novel, safe and effective TB vaccine for potential use in humans.
Topics: Adult; Child; Infant; Humans; Animals; Mice; Child, Preschool; Mycobacterium tuberculosis; BCG Vaccine; Adjuvants, Immunologic; Tuberculosis Vaccines; Tuberculosis, Pulmonary; Mycobacterium bovis; Saponins
PubMed: 38190806
DOI: 10.1080/21645515.2024.2302070 -
Virulence Dec 2024(APP) is an important pathogen of the porcine respiratory disease complex, which leads to huge economic losses worldwide. We previously demonstrated that -producing...
(APP) is an important pathogen of the porcine respiratory disease complex, which leads to huge economic losses worldwide. We previously demonstrated that -producing bovine neutrophil β-defensin-5 (B5) could resist the infection by the bovine intracellular pathogen . In this study, the roles of synthetic B5 in regulating mucosal innate immune response and protecting against extracellular APP infection were further investigated using a mouse model. Results showed that B5 promoted the production of tumour necrosis factor (TNF)-α, interleukin (IL)-1β, and interferon (IFN)-β in macrophages as well as dendritic cells (DC) and enhanced DC maturation . Importantly, intranasal B5 was safe and conferred effective protection against APP via reducing the bacterial load in lungs and alleviating pulmonary inflammatory damage. Furthermore, in the early stage of APP infection, we found that intranasal B5 up-regulated the secretion of TNF-α, IL-1β, IL-17, and IL-22; enhanced the rapid recruitment of macrophages, neutrophils, and DC; and facilitated the generation of group 3 innate lymphoid cells in lungs. In addition, B5 activated signalling pathways associated with cellular response to IFN-β and activation of innate immune response in APP-challenged lungs. Collectively, B5 via the intranasal route can effectively ameliorate the immune suppression caused by early APP infection and provide protection against APP. The immunization strategy may be applied to animals or human respiratory bacterial infectious diseases. Our findings highlight the potential importance of B5, enhancing mucosal defence against intracellular bacteria like APP which causes early-phase immune suppression.
Topics: Humans; Swine; Animals; Cattle; Immunity, Innate; Actinobacillus pleuropneumoniae; Lymphocytes; Lung; Tumor Necrosis Factor-alpha; Immunosuppression Therapy
PubMed: 38378464
DOI: 10.1080/21505594.2024.2316459 -
Microorganisms Oct 2023Hydroxamic acid (HA) derivatives display antibacterial and antifungal activities. HA with various numbers of carbon atoms (C, C, C, C, C and C), complexed with different...
Hydroxamic acid (HA) derivatives display antibacterial and antifungal activities. HA with various numbers of carbon atoms (C, C, C, C, C and C), complexed with different metal ions, including Fe(II/III), Ni(II), Cu(II) and Zn(II), were evaluated for their antimycobacterial activities and their anti-biofilm activities. Some derivatives showed antimycobacterial activities, especially in biofilm growth conditions. For example, 20-100 µM of HA10Fe2, HA10FeCl, HA10Fe3, HA10Ni2 or HA10Cu2 inhibited , BCG and biofilm development. HA10Fe2, HA12Fe2 and HA12FeCl could even attack pre-formed biofilms at higher concentrations (around 300 µM). The phthiocerol dimycocerosate (PDIM)-deficient H37Ra was more sensitive to the ion complexes of HA compared to other mycobacterial strains. Furthermore, HA10FeCl could increase the susceptibility of BCG to vancomycin. Proteomic profiles showed that the potential targets of HA10FeCl were mainly related to mycobacterial stress adaptation, involving cell wall lipid biosynthesis, drug resistance and tolerance and siderophore metabolism. This study provides new insights regarding the antimycobacterial activities of HA and their complexes, especially about their potential anti-biofilm activities.
PubMed: 37894269
DOI: 10.3390/microorganisms11102611 -
Veterinary Medicine and Science Jan 2024The European bison (Bison bonasus), a symbol of Polish nature, is a protected species that requires active health monitoring. However, conservation efforts are made...
BACKGROUND
The European bison (Bison bonasus), a symbol of Polish nature, is a protected species that requires active health monitoring. However, conservation efforts are made difficult by the zoonotic diseases such as brucellosis and tuberculosis.
OBJECTIVE
The aim of this study was to screen the Polish European bison population for exposure to the Mycobacterium tuberculosis complex (MTC) and Brucella spp.
METHODS
A total of 323 free-living and captive European bison from 13 localities were tested serologically for antibodies against the M. bovis P22 multi-protein complex (in-house ELISA) and against Brucella spp. (commercial ELISA).
RESULTS
Antibodies against the MTC (P22) were detected in 7% (22/323) of the tested European bison. Anti-MTC antibody positivity was not significantly different by sex, age, and captive/free range status. Anti-MTC antibodies were found in six of 13 populations sampled, always in populations with larger sample sizes including the four free-living ones. Antibodies against Brucella spp. were detected in 36% (116/323) of the tested bison. While Brucella spp. antibody prevalence was not different by sex, it was significantly different by age (lower in adults) and captive/free-living status. Brucella spp. seroprevalence decreased with sample size and seropositive bison were found in 12 of 13 sampling populations.
CONCLUSIONS
Our findings identify potential emerging threats to the European bison population and confirm the first serological response to P22 in European bison. As Poland is currently officially free of brucellosis and bovine tuberculosis, our results require careful interpretation. Further studies are needed to establish the presence of cross-reactions with atypical mycobacteria in the case of MTC and other bacteria (e.g. Yersinia enterocolitica O:9) in the case of Brucella spp.
Topics: Animals; Bison; Poland; Brucella; Mycobacterium tuberculosis; Seroepidemiologic Studies; Brucellosis; Antibodies, Bacterial
PubMed: 37943991
DOI: 10.1002/vms3.1314 -
Veterinary Research Mar 2024Tuberculosis BCG vaccination induced non-specific protective effects in humans led to postulate the concept of trained immunity (TRAIM) as an innate type of immune...
Tuberculosis BCG vaccination induced non-specific protective effects in humans led to postulate the concept of trained immunity (TRAIM) as an innate type of immune mechanism that triggered by a pathogen, protects against others. Killed vaccines have been considered not to be effective. However, field efficacy of a commercial vaccine against paratuberculosis, as well as of a recently developed M. bovis heat-inactivated vaccine (HIMB) prompted to test whether it could also induce TRAIM. To this, we used a sarcoptic mange rabbit model. Twenty-four weaned rabbits were treated orally or subcutaneously with a suspension of either HIMB (10 UFC) or placebo. Eighty-four days later the animals were challenged with approximately 5000 S. scabiei mites on the left hind limb. Skin lesion extension was measured every 2 weeks until 92 days post-infection (dpi). Two animals were killed at 77 dpi because of extensive skin damage. The rest were euthanized and necropsied and the lesion area and the mite burden per squared cm were estimated. Specific humoral immune responses to S. scabiei and to M. bovis were investigated with the corresponding specific ELISA tests. Subcutaneously and orally HIMB vaccinated animals compared with placebo showed reduced lesion scores (up to 74% and 62%, respectively) and mite counts (-170% and 39%, respectively). This, together with a significant positive correlation (r = 0.6276, p = 0.0031) between tuberculosis-specific antibodies and mite count at 92 dpi supported the hypothesis of non-specific effects of killed mycobacterial vaccination. Further research is needed to better understand this mechanism to maximize cross protection.
Topics: Humans; Rabbits; Animals; Mycobacterium bovis; Scabies; Tuberculosis; Enzyme-Linked Immunosorbent Assay; Immunity, Humoral; Vaccines, Inactivated; BCG Vaccine
PubMed: 38532491
DOI: 10.1186/s13567-024-01293-y -
Human Vaccines & Immunotherapeutics Dec 2023The BCG vaccine, like all other vaccines, is associated with adverse events following immunization (AEFI). Reducing the incidence of AEFI is crucial in reposing...
The BCG vaccine, like all other vaccines, is associated with adverse events following immunization (AEFI). Reducing the incidence of AEFI is crucial in reposing confidence in BCG vaccination and reducing hesitancy associated with the vaccine. This requires safety precautions before and during vaccinations, as well as reporting AEFIs after vaccination. This study assessed the adherence of health-care professionals to pre-vaccination precautions and adverse events following immunization (AEFI) reporting practices during BCG vaccination in four hospitals in Ghana. It is hoped that the findings of the study will serve as a baseline to identify gaps for further studies to generate a stronger evidence for policy formulation aimed at improving BCG vaccine safety in Ghana and other tuberculosis endemic countries. A cross-sectional study design was employed, and Statistical Package for Social Sciences, IBM® SPSS version 25 (SPSS Inc. USA) software was used for analysis. Chi-square and binary logistic regression tests were used to test the association between categorical variables and predictors of adherence to pre-BCG vaccination precautions, respectively, and a p-value of <.05 was considered statistically significant. The AEFIs commonly reported by mothers included abscess, injection site pain, injection site redness, fever, rash, muscle weakness, diarrhea, vomiting, coughing and rhinitis. Ninety-three participants (73.2%) were adherent to pre-BCG vaccination precautions. Ninety-two participants (72.4%) informed mothers to report all AEFIs encountered. Adherence to pre-BCG vaccination precautions and AEFI reporting were generally good; however, there is still room for improvement.
Topics: Female; Humans; Adverse Drug Reaction Reporting Systems; BCG Vaccine; Cross-Sectional Studies; Ghana; Immunization; Vaccination
PubMed: 37127290
DOI: 10.1080/21645515.2023.2199654 -
Microbiology Spectrum Aug 2023Tuberculosis (TB) is an ongoing threat to public health, and furthermore, the incidence of infections by nontuberculous mycobacteria (NTM), whose symptoms are not...
Tuberculosis (TB) is an ongoing threat to public health, and furthermore, the incidence of infections by nontuberculous mycobacteria (NTM), whose symptoms are not distinguishable from TB, is increasing globally, thus indicating a need for accurate diagnostics for patients with suspected mycobacterial infections. Such diagnostic strategies need to include two steps, (i) detecting the mycobacterial infections and, if the case is an NTM infection, (ii) identifying the causative NTM pathogen. To eliminate a false-positive TB diagnosis for a host vaccinated by the bacillus Calmette-Guérin (BCG) strain of Mycobacterium bovis, a new target specific for M. tuberculosis species was selected, together with the species-specific targets for the six dominant NTM species of clinical importance, i.e., M. intracellulare, M. avium, M. kansasii, M. massiliense, M. abscessus, and M. fortuitum. Using sets of primers and probes, a two-step real-time multiplex PCR method was designed. The diagnostic performance was assessed by using a total of 1,772 clinical specimens from patients with suspected TB or NTM infection. A total of 69.4% of M. tuberculosis and 28.8% of NTM infections were positive for the primary step of the real-time PCR corresponding to the culture within 10 weeks, and mycobacterial species of 75.5% of the NTM-positive cases were identified by the secondary step. The two-step method described herein presented promising results and similar diagnostic sensitivity and specificity to commercially available real-time PCR kits for detecting TB and NTM infections. The method also enabled the identification of mycobacterial species in three-quarters of NTM infection cases, thus providing a better treatment strategy. Tuberculosis (TB) is an ongoing threat to public health. In addition, infection by nontuberculous mycobacteria (NTM) is a nonnegligible issue for global public health, with increasing incidences. Since the antimicrobial treatment strategy needs to be differed by the causative pathogen, a rapid and accurate diagnostic method is necessary. In this study, we developed a two-step molecular diagnostic method using clinical specimens of TB and NTM infection-suspected patients. The diagnostic power of the new method using the novel target was similar to the widely used TB detection kit, and, among the NTM-positive specimens, three-quarters of the NTM species were able to be identified. This simple and powerful method will be useful as it is, and it could be applied easily to a point-of-care diagnostic apparatus for better application to patients, especially those living in developing countries.
Topics: Humans; Real-Time Polymerase Chain Reaction; Tuberculosis; Mycobacterium Infections, Nontuberculous; Nontuberculous Mycobacteria; Mycobacterium tuberculosis; Mycobacterium bovis
PubMed: 37378523
DOI: 10.1128/spectrum.01606-23