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88 results for “Mycobacteria”
Dataset / Code: Targeted protein degradation in mycobacteria uncovers antibacterial effects and potentiates antibiotic efficacy
<p><strong>Targeted protein degradation in mycobacteria uncovers antibacterial effects and potentiates antibiotic efficacy</strong></p> <p><strong> </strong></p> <p>Harim I. Won<sup>1,#</sup>, Samuel Zinga<sup>1,#</sup>, Olga Kandror<sup>1</sup>, Tatos Akopian<sup>1</sup>, Ian D. Wolf<sup>1</sup>, Jessica T.P. Schweber<sup>1</sup>, Ernst W. Schmid<sup>2</sup>, Michael C. Chao<sup>1</sup>, Maya Waldor<sup>1</sup>, Eric J. Rubin<sup>1,*</sup>, Junhao Zhu<sup>1,3,*</sup></p> <p><strong> </strong></p> <p><sup>1</sup>Department of Immunology and Infectious Diseases, Harvard T.H. Chan School of Public Health, Boston, Massachusetts 02115, USA.</p> <p><sup>2</sup>Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Blavatnik Institute, Boston, Massachusetts 02115, USA.</p> <p><sup>3</sup>CAS Key Laboratory of Pathogen Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences, Beijing, China.</p> <p><sup>#</sup>These authors contributed equally to this work.</p> <p>*Corresponding authors: <a href="mailto:zhujh@im.ac.cn">zhujh@im.ac.cn</a> (J.Z.), <a href="mailto:erubin@hsph.harvard.edu">erubin@hsph.harvard.edu</a> (E. J. R.)</p> <p><strong> </strong></p> <p><strong>Abstract</strong></p> <p>Proteolysis-targeting chimeras (PROTACs) represent a new therapeutic modality involving selectively directing disease-causing proteins for degradation through proteolytic systems. Our ability to exploit targeted protein degradation (TPD) for antibiotic development remains nascent due to our limited understanding of which bacterial proteins are amenable to a TPD strategy. Here, we use a genetic system to model chemically-induced proximity and degradation to screen essential proteins in <em>Mycobacterium smegmatis </em>(<em>Msm</em>)<em>, </em>a model for the human pathogen <em>M. tuberculosis </em>(<em>Mtb</em>). By integrating experimental screening of 72 protein candidates and machine learning, we find that drug-induced proximity to the bacterial ClpC1P1P2 proteolytic complex leads to the degradation of many endogenous proteins, especially those with disordered termini. Additionally, TPD of essential <em>Msm </em>proteins inhibits bacterial growth and potentiates the effects of existing antimicrobial compounds. Together, our results provide biological principles to select and evaluate attractive targets for future <em>Mtb</em> PROTAC development, as both standalone antibiotics and potentiators of existing antibiotic efficacy.</p> <p> </p>
Species-specific proteotypic peptides for characterization of non-tuberculosis mycobacteria
<p>Non-tuberculous mycobacteria are opportunistic bacteria that closely resemble <i>Mycobacterium tuberculosis,</i> causing respiratory infections in humans. While genotyping through genome sequencing is found accurate in detecting mycobacterial species but struggles with distinguishing bacterial co-infection. These challenges lead to delayed therapeutic intervention, drug resistance, and disease complications. Lately, mass spectrometry-based (MALDI-TOF-MS) proteomics has routinely been used in diagnosing mycobacterial species in clinical samples. However, it suffers accurate species detection owing to extensive bacterial cultures and poor specificity in polymicrobial infections. In contrast, due to its sensitivity, LC-MS/MS based proteomics is widely employed for accurate bacterial proteome mapping. In this study, in-depth proteomics of 9 NTM species with proteome database searches of 26 datasets was used. In total 20 million peptide spectrum matches were identified aiding to ≥40% proteome coverage in 7 NTMs with highest in <i>M. abscessus</i>. Further, metaproteomic analysis and rescoring of peptides resulted in high-confidence species-specificity proteotypic peptides in <i>M. smegmatis</i> (2342), <i>M. vaccae</i> (960), <i>M. abscessus</i> (75), <i>M. avium</i> subsp. <i>paratuberculosis</i> (3) and <i>M. fortuitum</i> (1). Finally, database search results were converted to spectral library format for easier future usage in targeted proteomic workflows. This workflow in deriving species-specific peptides with high confidence can be extended in distinguishing closely related bacterial species for enhancing microbial diagnostics.</p>
Supplemented material to "Mycobacteriosis in various pet and wild birds from Germany: pathological findings, coinfections, and characterisation of causative Mycobacteria."
<p>This is the supplemented material to the publication "Mycobacteriosis in Various Pet and Wild Birds from Germany: Pathological Findings, Coinfections, and Characterization of Causative Mycobacteria". <br>The causative agents and confounding factors of mycobacteriosis in a set of pet (n=45) and some wild birds (n=5) from Germany were examined in this study. Not only Mycobacterium genavense (Mg), but also M. avium subsp. avium (Maa) and M. avium subsp. hominissuis (Mah), contributed to mycobacteriosis in these birds. The isolates were characterized by a combination of different typing methods. The genetic diversity of isolates belonging to Mg, Maa and Mah differed. Various coinfections by viruses, endoparasites, fungi and other bacterial species did not affect the manifestation of mycobacteriosis. Cross pathological fidings were more often seen in mycobacteriosis caused by Ma compared to Mg suggesting a different pathogenicity of the two species. New genotypes of Mah were identified in these birds that is important for epidemiological studies and for understanding the zoonotic role of this pathogen, as the subsp. hominissuis represents an increasing public health concern. The study provides some evidence of correlation between individual Maa genotypes and virulence which will have to be confirmed by broader studies.</p>
Defining the genes required for survival of Mycobacterium bovis in the bovine host offers novel insights into the genetic basis of survival of pathogenic mycobacteria
<p>Supplementary dataset from "<strong><em>Defining the genes required for survival of Mycobacterium bovis in the bovine host offers novel insights into the genetic basis of survival of pathogenic mycobacteria</em></strong>"</p> <p> </p> <p><strong>Supplementary Figure legends</strong></p> <p><strong>Figure S1. Illustration of the transposon insertions around the <em>M. bovis </em>genome. </strong>Sequencing of the input library showed that transposon insertions were evenly distributed around the genome and 27,419 of the permissible 66,931 thymine–adenine dinucleotide (TA) sites contained an insertion representing an insertion density of ~41%. The outer ring are the genomic coordinates, the blue lines represent transposon insertions and the gray boxes indicate regions of that did not have any insertions. Plot made with Circlize (Gu et al, 2014).</p> <p> </p> <p><strong>Figure S2. Diversity of the output library isolated from lung and thoracic lymph node lesions compared to the input library. </strong>On average, libraries recovered from lung lesions contained 14,456 unique mutants and those recovered from the lymph nodes contained an average of 16,210 unique mutants. Insertion density is represented as a proportion of the TA sites that contained insertions. The numbers on the x-axis refer to the sequencing file from that sample and come from individual animals (Bioproject ID: PRJNA816175, Submission ID: SUB11067380).</p> <p> </p> <p><strong>Figure S3. Volcano plots showing the distribution of log<sub>2</sub> fold-changes and -log<sub>10</sub> of adjusted p-values for representative lung (A) and lymph node (B) samples. </strong>Adjusted p-values (BH-fdr correction) < 0.000001 cluster at the limits of the plot and precision reflects the number of resampling iterations (10,000).</p> <p> </p> <p><strong>Figure S4. Scatterplot of mean log<sub>2</sub> fold change per gene for all lung samples against all thoracic lymph node samples</strong>. Correlation between mean log<sub>2</sub> fold change among genes between the tissues was calculated with Spearman's ranked correlation, = 0.878, p-value < 2.2e-16.</p> <p> </p> <p><strong>Figure S5. Fold-changes caused by transposon insertions in <em>RD1<sup>BCG</sup></em> and <em>RD1<sup>MIC</sup> </em>in the lungs and lymph nodes of infected cattle. </strong>Boxplot for log<sub>2 </sub>fold-changes in genes of the RD1<sup>BCG</sup> region. Samples with adjusted p-values (BH-fdr corrected) <0.05 are indicated with purple points. Gene names highlighted in magenta have fewer than 5 TA sites located in the gene; too few to determine the statistical significance of changes in insertion levels with this method.</p> <p> </p> <p><strong>Supplementary Tables </strong></p> <p><strong>Table S1. Sequencing statistics of the input and output transposon libraries. </strong>The numbers in the column labelled “filename” refers to the sequencing file from that sample and come from individual animals (Bioproject ID: PRJNA816175, Submission ID: SUB11067380).</p> <p> </p> <p><strong>Table S2. Tissues collected and scored for gross pathology. </strong>Tissues from head and neck lymph nodes (from the right and left sub-mandibular lymph nodes, the right and left medial retropharyngeal lymph nodes), thoracic lymph nodes (the right and left bronchial lymph nodes, the cranial tracheobronchial lymph nodes, the cranial and caudal mediastinal lymph nodes) and from lung lesions, were collected and scored.</p> <p> </p> <p><strong>Table S3. Log<sub>2</sub> fold-changes for insertions across the entire genome of <em>M. bovis</em> AF2122/97. </strong>Cells are coloured according to log<sub>2</sub> fold-change. Refer to the text for the gene groups in individual tabs.</p> <p> </p> <p><strong>Table S4. </strong>Custom transposon sequencing primers and adaptors used in sequencing of the transposon libraries.</p> <p> </p>
Genetic analysis of mycobacteria isolated from suspect bovine tuberculosis lesions in Wolaita, Ethiopia - code and datasets.
<p>Bovine tuberculosis (bTB), caused by Mycobacterium bovis and other members of the Mycobacterium tuberculosis complex (MTBC), is a significant concern for livestock and public health in Ethiopia. This study aimed to assess the prevalence and causative agents of bTB in cattle from four abattoirs in the Wolaita region of Ethiopia. </p>
Databases for MyCodentifier: A tool for routine identification of nontuberculous mycobacteria using MGIT enriched shotgun metagenomics.
<p>Databases used for MyCodentifier a Nextflow pipeline to identify Mycobacterium tuberculosis complex (MTBC) and Nontuberculous mycobacteria (NTM) species from Next-generation sequencing (NGS) data.<br> <br> <strong>Short description:</strong><br> The pipeline is constructed using nextflow as workflow manager running in a docker container. It is able to identify species of MTBC/NTM from positive Mycobacterial Growth Indicator Tube (MGIT) cultures. To do so it uses an hsp65 database for fast identification coupled with a Metagenomic method using centrifuge to identify on genome level. For TB it also is able to identify subspecies. Results are presented in automated pdf and html reports.</p> <table> <caption><strong>Databases</strong></caption> <tbody> <tr> <td><strong>Name</strong></td> <td><strong>Short Description</strong></td> </tr> <tr> <td>20220726_ref.tar.gz</td> <td>7 major mycobacterial genomes as centrifuge classification database, used for reference-based mapping and genotype resistance prediction</td> </tr> <tr> <td>20220726_wgs_centrifuge_db_Radboudumc_MB.tar.gz</td> <td>centrifuge classification database using Tortoli <em>et al</em> 2017 Mycobacterium strains + additional strains</td> </tr> <tr> <td>genomes.tar.gz</td> <td>7 major mycobacterial genomes, annotation and Genbank files. Files are paired with 20220726_ref.tar.gz</td> </tr> <tr> <td>snpEff.tar.gz</td> <td>7 major mycobacterial genomes annotation models for snpEff.</td> </tr> <tr> <td>Tortoli_etal_hsp65.tar.gz</td> <td>KMA database of hsp65 gene extractions of the Tortoli <em>et al</em> 2017 Mycobacterium strains.</td> </tr> <tr> <td> <p>Used in the study:<br> p_compressed+h+v.tar.gz (12/06/2016)</p> </td> <td> <p>Databases available via <a>ftp://ftp.ccb.jhu.edu/pub/infphilo/centrifuge/data</a> or <a href="https://ccb.jhu.edu/software/centrifuge/manual.shtml#custom-database">https://ccb.jhu.edu/software/centrifuge/manual.shtml#custom-database</a></p> </td> </tr> </tbody> </table> <p><strong>MyCodentifier Github:</strong></p> <p><a href="https://jordycoolen.github.io/MyCodentifier/">https://jordycoolen.github.io/MyCodentifier/</a></p> <p> </p> <p> </p>
Global burden of non-tuberculous mycobacteria in the cystic fibrosis population: A systematic review and meta-analysis
<p><span><strong>Background</strong>:</span><span> People living with cystic fibrosis have an increased risk of lung infection with non-tuberculous mycobacteria (NTM), which is reportedly increasing. We conducted a systematic review of the literature to estimate the burden (prevalence and incidence) of non-tuberculous mycobacteria in the cystic fibrosis population. </span></p> <p><span><strong>Methods</strong>: Electronic databases, registries, and grey literature sources were searched for cohort and cross-sectional studies reporting epidemiological measures (incidence and prevalence) of NTM infection or NTM pulmonary disease (NTM-PD) in cystic fibrosis. The last search was conducted in September 2021; we included reports since database creation and registry reports published since 2010. The methodological quality of studies was appraised with the Joanna Briggs Institute tool. A random-effects meta-analysis was conducted to summarize the prevalence of NTM infection, and the remaining results are presented in a narrative synthesis. </span></p> <p><span><strong>Results</strong>: Ninety-five studies were included in this review. All 95 studies reported on NTM infection, and 14 of these also reported on NTM-PD. The pooled estimate for the point prevalence of NTM infection was 7.9% (CI 95%, 5.1–12.0%). In meta-regression, sample size and geographical location of the study modified the estimate. Longitudinal analysis of registry reports showed an increasing trend in NTM infection prevalence between 2010 and 2019. </span></p> <p><span><strong>Conclusions</strong>: The overall prevalence of NTM infection in CF is 7.9% and is increasing over time based on international registry reports. Future studies should report screening frequency, microbial identification methods, and incidence rates of progression from NTM infection to pulmonary disease.</span></p>
Global burden of non-tuberculous mycobacteria in the cystic fibrosis population: A systematic review and meta-analysis
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Data from: Mechanical morphotype switching as an adaptive response in Mycobacteria
<p><span>Invading microbes face a myriad of cidal mechanisms of phagocytes that inflict physical damage to microbial structures. How intracellular bacterial pathogens adapt to these stresses is not fully understood. Here, we report a new virulence mechanism by which changes to the mechanical stiffness of the mycobacterial cell surface confers refraction to killing during infection. Long-Term Time-Lapse Atomic Force Microscopy was used to reveal a process of "mechanical morphotype switching" in mycobacteria exposed to host intracellular stress. A "soft" mechanical morphotype switch enhances tolerance to intracellular macrophage stress, including cathelicidin. Both pharmacologic treatment, with bedaquiline, and a genetic mutant lacking <em>uvrA</em> modified the basal mechanical state of mycobacteria into a "soft" mechanical morphotype, enhancing survival in macrophages. Our study proposes microbial cell mechanical adaptation as a critical axis for surviving host-mediated stressors.</span></p>
Nontuberculous mycobacteria persistence in a cell model mimicking alveolar macrophages (genome assembly and annotation dataset)
<p>This dataset includes the assembled contigs (.fasta and .gbk files), the nucleotide sequences of the prediction transcripts (CDS, rRNA, tRNA, tmRNA, misc_RNA) (.ffn files) and the respective amino acid sequences of the translated CDS sequences (.faa files) for the following Nontuberculous mycobacteria (NTM) strains: <em>Mycobacterium smegmatis </em>mc<sup>2</sup>155 (reference strain), <em>Mycobacterium avium</em> ATCC25921 (reference strain), <em>M. avium </em>60/08 (clinical strain), <em>Mycobacterium fortuitum</em> ATCC6841 (reference strain) and <em>M. fortuitum</em> 747/08 (clinical strain).</p> <p>All raw sequence reads used in this study were deposited in the European Nucleotide Archive (ENA) (BioProject PRJEB30455).</p> <p>The associated article can be found here: <a href="https://www.ncbi.nlm.nih.gov/pubmed/31035520">https://www.ncbi.nlm.nih.gov/pubmed/31035520</a></p> <p> </p>
Prospective Healthcare-Associated Links in Transmission of Nontuberculous Mycobacteria
ClinicalTrials.gov study NCT05686837. IPD Sharing: YES. Countries: 1. Publications: 6.
Liposomal Amikacin for Inhalation (LAI) for Nontuberculous Mycobacteria
ClinicalTrials.gov study NCT01315236. IPD Sharing: Not stated. Countries: 2. Publications: 2.
Transmission and Acquisition of Nontuberculous Mycobacteria Outbreak Investigation (TrANsMIt)
ClinicalTrials.gov study NCT06155747. IPD Sharing: YES. Countries: 1. Publications: 3.
Sequencing Mycobacteria and Algorithm-determined Resistant Tuberculosis Treatment Trial
ClinicalTrials.gov study NCT05017324. IPD Sharing: YES. Countries: 1. Publications: 1.
Confocal images for Mycobacteria biofilm from: Lipoarabinomannan regulates septation in Mycobacterium smegmatis
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Integrative genomics of the mammalian alveolar macrophage response to intracellular mycobacteria: RNA-seq statistics and results
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Data from: Mechanical morphotype switching as an adaptive response in Mycobacteria
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Targeted metabolomics data for riboflavin, FMN and FAD in <em>Mycobacteria tuberculosis</em> and <em>Mycolicibacterium smegmatis</em>
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Myeloid ATG7 Functions as a Sentinel for Pulmonary Defense Against Infection with Nontuberculous Mycobacteria
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Tigecycline for Treatment of Rapidly Growing Mycobacteria
ClinicalTrials.gov study NCT00600600. IPD Sharing: NO. Countries: 1. Publications: 1.
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Allen Brain Atlas
Allen Brain Atlas is an Allen Institute collection of brain map atlases, datasets, APIs, and analysis tools covering mouse, human, and non-human primate brain resources.
Annotated Behaviour and Observability Dataset (ABODe)
ABODe is a University of Edinburgh DataShare dataset for behavior classification in group-housed mice using home-cage video, identities, bounding boxes, ground-plate positions, and annotator labels.
DANDI Archive for NWB datasets
DANDI is a BRAIN Initiative archive for publishing and sharing neurophysiology data, including electrophysiology, optophysiology, and behavioral data packaged as NWB and related standards.
International Brain Laboratory public data
The International Brain Laboratory public data releases expose standardized mouse decision-making experiments, including Neuropixels recordings, widefield calcium imaging, behavior, and session metadata accessed through the ONE API.
OpenNeuro
OpenNeuro is a free, open platform for sharing neuroimaging datasets, with public search, dataset pages, and download paths for web, S3, DataLad, and the OpenNeuro CLI.