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Microbiology Resource Announcements Apr 2024, a slow-growing Actinobacterium, typically induces tuberculosis-like disease in fish. Here, we report a new reference sequence for ATCC 927, along with its DNA...
, a slow-growing Actinobacterium, typically induces tuberculosis-like disease in fish. Here, we report a new reference sequence for ATCC 927, along with its DNA methylome. This aims to maximize the research potential of this type strain and facilitates investigations into the pathomechanisms of human tuberculosis.
PubMed: 38415640
DOI: 10.1128/mra.01016-23 -
Microorganisms Feb 2024Tuberculosis (TB) is caused by infection with (), which has a unique resistance to many antimicrobial agents. TB has emerged as a significant worldwide health issue...
Tuberculosis (TB) is caused by infection with (), which has a unique resistance to many antimicrobial agents. TB has emerged as a significant worldwide health issue because of the rise of multidrug-resistant strains causing drug-resistant TB (DR-TB). As a result, the development of new drugs or effective strategies is crucial for patients with TB. () and are both species of mycobacteria. In zebrafish, proliferates and forms chronic granulomatous infections, which are similar to infections in lung tissue. Syringaldehyde (SA) is a member of the phenolic aldehyde family found in various plants. Here, we investigated its antioxidative and antibacterial properties in -infected cells and zebrafish. Our results demonstrated that SA inhibits -infected pulmonary epithelial cells and inhibits the proliferation of in -infected zebrafish, suggesting that SA provides an antibacterial effect during infection. Further study demonstrated that supplementation with SA inhibits the production of malondialdehyde (MDA) and reactive oxygen species (ROS) and increases the levels of reduced glutathione (GSH) in -infection-induced macrophages. SA inhibits the levels of MDA in -infected zebrafish, suggesting that SA exerts antioxidative effects in vivo. Additionally, we found that SA promotes the expression of NRF2/HO-1/NQO-1 and the activation of the AMPK-α1/AKT/GSK-3β signaling pathway. In summary, our data demonstrated that SA exerts antioxidative and antibacterial effects during infection both in vivo and in vitro and that the antioxidative effects of SA may be due to the regulation of NRF2/HO-1/NQO-1 and the AMPK-α1/AKT/GSK-3β signaling pathway.
PubMed: 38399751
DOI: 10.3390/microorganisms12020348 -
PloS One 2024Retinoic acid inducible gene I (Rig-I) is a cytosolic pattern recognition receptor canonically described for its important role in sensing viral RNAs. Increasingly,...
Retinoic acid inducible gene I (Rig-I) is a cytosolic pattern recognition receptor canonically described for its important role in sensing viral RNAs. Increasingly, bacterially-derived RNA from intracellular bacteria such as Mycobacterium tuberculosis, have been shown to activate the same host Rig-I/Mitochondrial antiviral sensing protein (MAVS) signaling pathway to drive a type-I interferon response that contributes to bacterial pathogenesis in vivo. In M. tuberculosis, this response is mediated by the protein secretion system SecA2, but little is known about whether this process is conserved in other pathogenic mycobacteria or the mechanism by which these nucleic acids gain access to the host cytoplasm. Because the M. tuberculosis and M. marinum SecA2 protein secretion systems share a high degree of genetic and functional conservation, we hypothesized that Rig-I/MAVS activation and subsequent induction of IFN-β secretion by host macrophages will also be conserved between these two mycobacterial species. To test this, we generated a ΔsecA2 M. marinum strain along with complementation strains expressing either the M. marinum or M. tuberculosis secA2 genes. Our results suggest that the ΔsecA2 strain has a growth defect in vitro but not in host macrophages. These intracellular growth curves also suggested that the calculation applied to estimate the number of bacteria added to macrophage monolayers in infection assays underestimates bacterial inputs for the ΔsecA2 strain. Therefore, to better examine secreted IFN-β levels when bacterial infection levels are equal across strains we plated bacterial CFUs at 2hpi alongside our ELISA based infections. This enabled us to normalize secreted levels of IFN-β to a standard number of bacteria. Applying this approach to both WT and MAVS-/- bone marrow derived macrophages we observed equal or higher levels of secreted IFN-β from macrophages infected with the ΔsecA2 M. marinum strain as compared to WT. Together our findings suggest that activation of host Rig-I/MAVS cytosolic sensors and subsequent induction of IFN-β response in a SecA2-dependent manner is not conserved in M. marinum under the conditions tested.
Topics: Humans; Mycobacterium tuberculosis; Mycobacterium marinum; Signal Transduction; Macrophages; DEAD Box Protein 58; Tuberculosis
PubMed: 38394154
DOI: 10.1371/journal.pone.0281564 -
Emerging Microbes & Infections Dec 2024The discovery of promising cytokines and clarification of their immunological mechanisms in controlling the intracellular fate of (Mtb) are necessary to identify...
The discovery of promising cytokines and clarification of their immunological mechanisms in controlling the intracellular fate of (Mtb) are necessary to identify effective diagnostic biomarkers and therapeutic targets. To escape immune clearance, Mtb can manipulate and inhibit the normal host process of phagosome maturation. Phagosome maturation arrest by Mtb involves multiple effectors and much remains unknown about this important aspect of Mtb pathogenesis. In this study, we found that interleukin 16 (IL-16) is elevated in the serum samples of Tuberculosis (TB) patients and can serve as a specific target for treatment TB. There was a significant difference in IL-16 levels among active TB, latent TB infection (LTBI), and non-TB patients. This study first revealed that macrophages are the major source of IL-16 production in response to Mtb infection, and elucidated that IL-16 can promote Mtb intracellular survival by inhibiting phagosome maturation and suppressing the expression of Rev-erbα which can inhibit IL-10 secretion. The experiments using zebrafish larvae infected with and mice challenged with H37Rv demonstrated that reducing IL-16 levels resulted in less severe pathology and improved survival, respectively. In conclusion, this study provided direct evidence that Mtb hijacks the host macrophages-derived interleukin 16 to enhance intracellular growth. It is suggesting the immunosuppressive role of IL-16 during Mtb infection, supporting IL-16 as a promising therapeutic target.
Topics: Animals; Humans; Mice; Interleukin-16; Macrophages; Mycobacterium tuberculosis; Phagosomes; Tuberculosis; Zebrafish
PubMed: 38380651
DOI: 10.1080/22221751.2024.2322663 -
Fish & Shellfish Immunology Apr 2024IFN-γ plays a crucial role in both innate and adaptive immune responses and is a typical Th1 cytokine that promotes Th1 response and activates macrophages. When...
IFN-γ plays a crucial role in both innate and adaptive immune responses and is a typical Th1 cytokine that promotes Th1 response and activates macrophages. When macrophages were incubated with IFN-γ, their phagocytosis ratio against Mycobacterium marinum increased significantly, as observed under fluorescence microscopy. The macrophages engulfed a large number of M. marinum. The proliferative ability of macrophages treated with IFN-γ was significantly weaker on the 4th and 7th day after phagocytosis and subsequent re-infection with marine chlamydia (P < 0.001). This suggests that IFN-γ enhances the phagocytosis and killing ability of macrophages against M. marinum. IFN-γ protein also significantly increased the production of reactive oxygen species (HO) and nitric oxide (NO) by macrophages. Additionally, the expression levels of toll-like receptor 2 (tlr2) and caspase 8 (casp8) were significantly higher in macrophages after IFN-γ incubation compared to direct infection after 12 h of M. marinum stimulation. Apoptosis was also observed to a higher degree in IFN-γ incubated macrophage. Moreover, mRNA expression of major histocompatibility complex (MHC) molecules produced by macrophages after IFN-γ incubation was significantly higher than direct infection. This indicates that IFN-γ enhances antigen presentation by upregulating MHC expression. It also upregulates tlr2 and casp8 expression through the TLR2 signaling pathway to induce apoptosis in macrophages. The pro-inflammatory cytokine showed an initial increase followed by a decline, suggesting that IFN-γ enhances the immune response of macrophages against M. marinum infection. On the other hand, the anti-inflammatory cytokine showed a delayed increase, significantly reducing the expression of pro-inflammatory cytokines. The expression of both cytokines balanced each other and together regulated the inflammatory reaction against M. marinum infection.
Topics: Animals; Toll-Like Receptor 2; Mycobacterium marinum; Hydrogen Peroxide; Macrophages; Cytokines
PubMed: 38369071
DOI: 10.1016/j.fsi.2024.109436 -
Journal of Proteome Research Mar 2024Nontuberculous mycobacteria are opportunistic bacteria pulmonary and extra-pulmonary infections in humans that closely resemble . Although genome sequencing strategies...
Discovery of Species-Specific Proteotypic Peptides To Establish a Spectral Library Platform for Identification of Nontuberculosis Mycobacteria from Mass Spectrometry-Based Proteomics.
Nontuberculous mycobacteria are opportunistic bacteria pulmonary and extra-pulmonary infections in humans that closely resemble . Although genome sequencing strategies helped determine NTMs, a common assay for the detection of coinfection by multiple NTMs with in the primary attempt of diagnosis is still elusive. Such a lack of efficiency leads to delayed therapy, an inappropriate choice of drugs, drug resistance, disease complications, morbidity, and mortality. Although a high-resolution LC-MS/MS-based multiprotein panel assay can be developed due to its specificity and sensitivity, it needs a library of species-specific peptides as a platform. Toward this, we performed an analysis of proteomes of 9 NTM species with more than 20 million peptide spectrum matches gathered from 26 proteome data sets. Our metaproteomic analyses determined 48,172 species-specific proteotypic peptides across 9 NTMs. Notably, (26,008), (12,442), (6487), (1623), subsp. (844), subsp. (580), and (112) displayed >100 species-specific proteotypic peptides. Finally, these peptides and corresponding spectra have been compiled into a spectral library, FASTA, and JSON formats for future reference and validation in clinical cohorts by the biomedical community for further translation.
Topics: Animals; Humans; Proteomics; Chromatography, Liquid; Tandem Mass Spectrometry; Nontuberculous Mycobacteria; Mycobacterium tuberculosis; Peptides
PubMed: 38358903
DOI: 10.1021/acs.jproteome.3c00850 -
Veterinary Pathology Jul 2024ecovar Liflandii (Liflandii) was identified as the causative agent of mycobacteriosis in a research colony of Zaire dwarf clawed frogs () at the University of Michigan....
ecovar Liflandii (Liflandii) was identified as the causative agent of mycobacteriosis in a research colony of Zaire dwarf clawed frogs () at the University of Michigan. Clinical presentation included lethargy, generalized septicemia, cutaneous granulomas, coelomic effusion, and acute mortality. Identification of the mycobacterial species was based on molecular, microbiological, and histopathologic characteristics. These findings indicate that Liflandii is a primary cause of morbidity and mortality in Zaire dwarf clawed frogs and should be considered in the differential diagnosis of sepsis and coelomic effusion in amphibians. Mycobacterial speciation is important given the variability in pathogenesis within the family and the implications for both animal and human health as potential zoonoses. The Zaire dwarf clawed frog is a species common in the pet trade, and these findings provide consideration for this pathogen as a potentially important public health concern. This is the first report of Liflandii infection in the genus and illustrates the diagnostic challenges of differentiating among both mycolactone-producing mycobacteria and . Furthermore, we demonstrate the utility of environmental sampling for this pathogen within the tank system, suggesting this mode of sampling could replace the need for direct frog surveillance.
Topics: Animals; Mycobacterium Infections, Nontuberculous; Mycobacterium ulcerans; Anura
PubMed: 38345017
DOI: 10.1177/03009858241230103 -
Water Research Apr 2024Tracking nitrogen pollution sources is crucial for the effective management of water quality; however, it is a challenging task due to the complex contaminative...
Tracking nitrogen pollution sources is crucial for the effective management of water quality; however, it is a challenging task due to the complex contaminative scenarios in the freshwater systems. The contaminative pattern variations can induce quick responses of aquatic microorganisms, making them sensitive indicators of pollution origins. In this study, the soil and water assessment tool, accompanied by a detailed pollution source database, was used to detect the main nitrogen pollution sources in each sub-basin of the Liuyang River watershed. Thus, each sub-basin was assigned to a known class according to SWAT outputs, including point source pollution-dominated area, crop cultivation pollution-dominated area, and the septic tank pollution-dominated area. Based on these outputs, the random forest (RF) model was developed to predict the main pollution sources from different river ecosystems using a series of input variable groups (e.g., natural macroscopic characteristics, river physicochemical properties, 16S rRNA microbial taxonomic composition, microbial metagenomic data containing taxonomic and functional information, and their combination). The accuracy and the Kappa coefficient were used as the performance metrics for the RF model. Compared with the prediction performance among all the input variable groups, the prediction performance of the RF model was significantly improved using metagenomic indices as inputs. Among the metagenomic data-based models, the combination of the taxonomic information with functional information of all the species achieved the highest accuracy (0.84) and increased median Kappa coefficient (0.70). Feature importance analysis was used to identify key features that could serve as indicators for sudden pollution accidents and contribute to the overall function of the river system. The bacteria Rhabdochromatium marinum, Frankia, Actinomycetia, and Competibacteraceae were the most important species, whose mean decrease Gini indices were 0.0023, 0.0021, 0.0019, and 0.0018, respectively, although their relative abundances ranged only from 0.0004 to 0.1 %. Among the top 30 important variables, functional variables constituted more than half, demonstrating the remarkable variation in the microbial functions among sites with distinct pollution sources and the key role of functionality in predicting pollution sources. Many functional indicators related to the metabolism of Mycobacterium tuberculosis, such as K24693, K25621, K16048, and K14952, emerged as significant important factors in distinguishing nitrogen pollution origins. With the shortage of pollution source data in developing regions, this suggested approach offers an economical, quick, and accurate solution to locate the origins of water nitrogen pollution using the metagenomic data of microbial communities.
Topics: Nitrogen; Rivers; RNA, Ribosomal, 16S; Water Pollution; Microbiota; Environmental Monitoring; China; Water Pollutants, Chemical
PubMed: 38341971
DOI: 10.1016/j.watres.2024.121255 -
Mayo Clinic Proceedings Feb 2024
Topics: Humans; Mycobacterium marinum; Mycobacterium Infections, Nontuberculous; Mycobacterium tuberculosis
PubMed: 38309933
DOI: 10.1016/j.mayocp.2023.08.005 -
Life Science Alliance Apr 2024Regulation of host miRNA expression is a contested node that controls the host immune response to mycobacterial infection. The host must counter subversive efforts of...
Regulation of host miRNA expression is a contested node that controls the host immune response to mycobacterial infection. The host must counter subversive efforts of pathogenic mycobacteria to launch a protective immune response. Here, we examine the role of miR-126 in the zebrafish- infection model and identify a protective role for infection-induced miR-126 through multiple effector pathways. We identified a putative link between miR-126 and the and signalling axes resulting in the suppression of non- expressing macrophage accumulation at early granulomas. Mechanistically, we found a detrimental effect of expression that renders zebrafish embryos susceptible to higher bacterial burden and increased cell death via mTOR inhibition. We found that macrophage recruitment driven by the signalling axis was at the expense of the recruitment of classically activated -expressing macrophages and increased cell death around granulomas. Together, our results delineate putative pathways by which infection-induced miR-126 may shape an effective immune response to infection in zebrafish embryos.
Topics: Animals; Granuloma; Macrophages; MicroRNAs; Mycobacterium Infections, Nontuberculous; Zebrafish; Tuberous Sclerosis Complex 1 Protein; Chemokine CXCL12; Zebrafish Proteins
PubMed: 38307625
DOI: 10.26508/lsa.202302523