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  • 1
    Online Resource
    Online Resource
    Updated Reference Genome Sequence and Annotation of Mycobacterium bovis AF2122/97
    American Society for Microbiology ; 2017
    In:  Genome Announcements Vol. 5, No. 14 ( 2017-04-06)
    Details
    In: Genome Announcements, American Society for Microbiology, Vol. 5, No. 14 ( 2017-04-06)
    Abstract: We report here an update to the reference genome sequence of the bovine tuberculosis bacillus Mycobacterium bovis AF2122/97, generated using an integrative multiomics approach. The update includes 42 new coding sequences (CDSs), 14 modified annotations, 26 single-nucleotide polymorphism (SNP) corrections, and disclosure that the RD900 locus, previously described as absent from the genome, is in fact present.
    Type of Medium: Online Resource
    ISSN: 2169-8287
    URL: Article
    DOI: 10.1128/genomeA.00157-17
    Language: English
    Publisher: American Society for Microbiology
    Publication Date: 2017
    detail.hit.zdb_id: 2968655-6
    detail.hit.zdb_id: 2704277-7
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  • 2
    Online Resource
    Online Resource
    Expression Dysregulation as a Mediator of Fitness Costs in Antibiotic Resistance
    American Society for Microbiology ; 2021
    In:  Antimicrobial Agents and Chemotherapy Vol. 65, No. 9 ( 2021-08-17)
    Details
    In: Antimicrobial Agents and Chemotherapy, American Society for Microbiology, Vol. 65, No. 9 ( 2021-08-17)
    Abstract: Antimicrobial resistance (AMR) poses a threat to global health and the economy. Rifampicin-resistant Mycobacterium tuberculosis accounts for a third of the global AMR burden. Gaining the upper hand on AMR requires a deeper understanding of the physiology of resistance. AMR often results in a fitness cost in the absence of drug. Identifying the molecular mechanisms underpinning this cost could help strengthen future treatment regimens. Here, we used a collection of M. tuberculosis strains that provide an evolutionary and phylogenetic snapshot of rifampicin resistance and subjected them to genome-wide transcriptomic and proteomic profiling to identify key perturbations of normal physiology. We found that the clinically most common rifampicin resistance-conferring mutation, RpoB Ser450Leu, imparts considerable gene expression changes, many of which are mitigated by the compensatory mutation in RpoC Leu516Pro. However, our data also provide evidence for pervasive epistasis—the same resistance mutation imposed a different fitness cost and functionally distinct changes to gene expression in genetically unrelated clinical strains. Finally, we report a likely posttranscriptional modulation of gene expression that is shared in most of the tested strains carrying RpoB Ser450Leu, resulting in an increased abundance of proteins involved in central carbon metabolism. These changes contribute to a more general trend in which the disruption of the composition of the proteome correlates with the fitness cost of the RpoB Ser450Leu mutation in different strains.
    Type of Medium: Online Resource
    ISSN: 0066-4804 , 1098-6596
    URL: Article
    DOI: 10.1128/AAC.00504-21
    RVK:
    XA 24552
    Language: English
    Publisher: American Society for Microbiology
    Publication Date: 2021
    detail.hit.zdb_id: 1496156-8
    SSG: 12
    SSG: 15,3
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  • 3
    Online Resource
    Online Resource
    Mycobacterium tuberculosis in the Proteomics Era
    American Society for Microbiology ; 2014
    In:  Microbiology Spectrum Vol. 2, No. 2 ( 2014-03-14)
    Details
    In: Microbiology Spectrum, American Society for Microbiology, Vol. 2, No. 2 ( 2014-03-14)
    Abstract: The emerging field of proteomics has contributed greatly to improving our understanding of the human pathogen Mycobacterium tuberculosis over the last two decades. In this chapter we provide a comprehensive overview of mycobacterial proteome research and highlight key findings. First, studies employing a combination of two-dimensional gel electrophoresis and mass spectrometry (MS) provided insights into the proteomic composition, initially of the whole bacillus and subsequently of subfractions, such as the cell wall, cytosol, and secreted proteins. Comparison of results obtained under various culture conditions, i.e., acidic pH, nutrient starvation, and low oxygen tension, aiming to mimic facets of the intracellular lifestyle of M. tuberculosis, provided initial clues to proteins relevant for intracellular survival and manipulation of the host cell. Further attempts were aimed at identifying the biological functions of the hypothetical M. tuberculosis proteins, which still make up a quarter of the gene products of M. tuberculosis , and at characterizing posttranslational modifications. Recent technological advances in MS have given rise to new methods such as selected reaction monitoring (SRM) and data-independent acquisition (DIA). These targeted, cutting-edge techniques combined with a public database of specific MS assays covering the entire proteome of M. tuberculosis allow the simple and reliable detection of any mycobacterial protein. Most recent studies attempt not only to identify but also to quantify absolute amounts of single proteins in the complex background of host cells without prior sample fractionation or enrichment. Finally, we will discuss the potential of proteomics to advance vaccinology, drug discovery, and biomarker identification to improve intervention and prevention measures for tuberculosis.
    Type of Medium: Online Resource
    ISSN: 2165-0497
    URL: Article
    DOI: 10.1128/microbiolspec.MGM2-0020-2013
    Language: English
    Publisher: American Society for Microbiology
    Publication Date: 2014
    detail.hit.zdb_id: 2807133-5
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  • 4
    Online Resource
    Online Resource
    All Driven by Energy Demand? Integrative Comparison of Metabolism of Enterococcus faecalis Wildtype and a Glutamine Synthase Mutant
    American Society for Microbiology ; 2022
    In:  Microbiology Spectrum Vol. 10, No. 2 ( 2022-04-27)
    Details
    In: Microbiology Spectrum, American Society for Microbiology, Vol. 10, No. 2 ( 2022-04-27)
    Abstract: Lactic acid bacteria (LAB) play a significant role in biotechnology, e.g., food industry and also in human health. Many LAB genera have developed a multidrug resistance in the past few years, causing a serious problem in controlling hospital germs worldwide. Enterococcus faecalis accounts for a large part of the human infections caused by LABs. Therefore, studying its adaptive metabolism under various environmental conditions is particularly important to promote the development of new therapeutic approaches. In this study, we investigated the effect of glutamine auxotrophy (Δ glnA mutant) on metabolic and proteomic adaptations of E. faecalis in response to a changing pH in its environment. Changing pH values are part of the organism’s natural environment in the human body and play a role in the food industry. We compared the results with those of the wildtype. Using a genome-scale metabolic model constrained by metabolic and proteomic data, our integrative method allows us to understand the bigger picture of the adaptation strategies of this bacterium. The study showed that energy demand is the decisive factor in adapting to a new environmental pH. The energy demand of the mutant was higher at all conditions. It has been reported that Δ glnA mutants of bacteria are energetically less effective. With the aid of our data and model we are able to explain this phenomenon as a consequence of a failure to regulate glutamine uptake and the costs for the import of glutamine and the export of ammonium. Methodologically, it became apparent that taking into account the nonspecificity of amino acid transporters is important for reproducing metabolic changes with genome-scale models because it affects energy balance. IMPORTANCE The integration of new pH-dependent experimental data on metabolic uptake and release fluxes, as well as of proteome data with a genome-scale computational model of a glutamine synthetase mutant of E. faecalis is used and compared with those of the wildtype to understand why glutamine auxotrophy results in a less efficient metabolism and how—in comparison with the wildtype—the glutamine synthetase knockout impacts metabolic adjustments during acidification or simply exposure to lower pH. We show that forced glutamine auxotrophy causes more energy demand and that this is likely due to a disregulated glutamine uptake. Proteome changes during acidification observed for the mutant resemble those of the wildtype with the exception of glycolysis-related genes, as the mutant is already energetically stressed at a higher pH and the respective proteome changes were in effect.
    Type of Medium: Online Resource
    ISSN: 2165-0497
    URL: Article
    DOI: 10.1128/spectrum.02400-21
    Language: English
    Publisher: American Society for Microbiology
    Publication Date: 2022
    detail.hit.zdb_id: 2807133-5
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  • 5
    Online Resource
    Online Resource
    Epigenetics and Proteomics Join Transcriptomics in the Quest for Tuberculosis Biomarkers
    American Society for Microbiology ; 2015
    In:  mBio Vol. 6, No. 5 ( 2015-10-30)
    Details
    In: mBio, American Society for Microbiology, Vol. 6, No. 5 ( 2015-10-30)
    Abstract: DNA methylation modifies the transcriptional program of cells. We have focused on two major populations of leukocytes involved in immune response to infectious diseases, granulocytes and monocytes, both of which are professional phagocytes that engulf and kill bacteria. We have interrogated how DNA methylation, gene expression, and protein translation differ in these two cell populations between healthy individuals and patients suffering from TB. To better understand the underlying biologic mechanisms, we harnessed a statistical enrichment analysis, taking advantage of predefined and well-characterized gene sets. Not only were there clear differences on various levels between the two populations, but there were also differences between TB patients and healthy controls in the transcriptome, proteome, and, for the first time, DNA methylome in these cells. Our pilot study emphasizes the value of a large-scale study of the DNA methylome taking into account our findings.
    Type of Medium: Online Resource
    ISSN: 2161-2129 , 2150-7511
    URL: Article
    DOI: 10.1128/mBio.01187-15
    Language: English
    Publisher: American Society for Microbiology
    Publication Date: 2015
    detail.hit.zdb_id: 2557172-2
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