Molecular and Experimental Mycobacteriology
The fight against tuberculosis (TB) and other lung diseases based on a better understanding of the causative agents. In the main focus of the Research Group (RG) are M. tuberculosis complex strains (Mtbc) and other bacterial lung pathogens. The translational research agenda comprises the following topics: local and global transmission dynamics, determination of resistance and compensatory mechanisms, population structure and evolution of Mtbc-strains and other mycobacteria, virulence/physiology/pathobiology of mycobacteria, application of high through put technologies in research and diagnostics as well as for individualized therapy and evolutionary medicine (Fig.1).
The successful work of the research group is based on an excellent methodological expertise. Next generation sequencing (NGS) approaches are applied for high resolution characterization of pathogen genomes and transcriptomes. More than 300 strains per weak are currently under investigation in our pathogenomic laboratory and overall, genome data of more than 15.000 Mtbc-strains and of other lung pathogens are available for downstream analyses. In line with the increasing amount of genome sequencing data, IT-infrastructure (e.g. server, storage) and bioinformatic data analysis pipeline have been set up and are constantly further developed. In the pathobiology laboratory, in vitro and in vivo models are available to analyze Mtbc-strains in clinical relevant stress conditions (dormancy, antibiotic stress, infection) with connected pipelines for the analysis of DNA, RNA and proteins. The validation of relevant target genes e.g. involved in virulence or resistance is possible by established “knock in” or “knock out” approaches.
Research interests of the working group are focused on the analysis of the epidemiology of tuberculosis (TB) by applying molecular epidemiological tools, the analysis of resistance mechanisms, the analysis of the global population structure, genomic diversity and virulence, and the microevolution of clinical M. tuberculosis complex isolates.
These main focuses of research are described in more detail in the following.
Molecular epidemiology:
All “gold standard” methods for molecular typing of M. tuberculosis complex isolates are available for molecular epidemiological studies. In recent years, we have already carried out several studies on the epidemiology of TB in different settings that provided e.g. for the first time precise data on transmission dynamics of TB strains, risk factors for recent transmission or the spread of multidrug resistant strains in Germany. In the coming years, ongoing and newly initiated molecular epidemiological studies will be focused on hot topic research questions e.g. the analysis of specific pathogenic properties of strains of particular phylogenetic lineages (e.g. the Beijing genotype) such as a higher virulence or an enhanced propensity to acquire drug resistance. To address these questions, already established population based investigations in Germany will be continued as longitudinal model studies for low incidence countries. Furthermore, the initiation of studies in high incidence countries with a focus on Eastern Europe is intended. All strains will be archived and provide a unique bio bank for future research studies.
Resistance mechanisms:
The investigation of resistance mechanisms of clinical M. tuberculosis isolates has long been a main focus of research that should be continued and intensified in the next years. In addition to classical analysis methods, new tools for comparative genomics such as ultra fast massively parallel genome sequencing will be used to decipher new resistance mechanisms.
The significance of genetic variants for the development of particular resistances will be validated by screening of available strain collections and by generating isogenic mutants by allelic exchange that can be further investigated in vitro and in vivo in the mouse model for the presence of phenotypic resistance (in co-operation with the group of S. Ehlers).
Further studies aim to improve the detection of resistance conferring mutations by new detection systems e.g. micro arrays.
Global population structure, genomic diversity and virulence.
There is growing evidence that the genetic heterogeneity of M. tuberculosis complex isolates is greater than previously thought, and influences the transmissibility and virulence of clinical isolates as well as the immune response and clinical picture they evoke. Clinical TB, then, must be seen as the result of specific, genetically determined pathogenicity traits of mycobacteria encountering specific, genetically determined defects in antimycobacterial pathways of the patient. Ongoing studies applying high resolution genomic markers have already revealed insights into the global population structure of the M. tuberculosis complex that is composed of several phylogenetic lineages with large difference in geographical prevalence. Based on this, we have established a reference collection of well characterized clinical isolates representing the major phylogenetic lineages. These will be used to further explore the level of genomic diversity by comparative genome, transcriptome and proteome studies. Selected strains will be analyzed in infection model systems to investigate the importance of genomic diversity for differences in virulence and host-pathogen interaction.
Microevolution
Clinical M. tuberculosis complex isolates are characterized by a relative low level of genomic variation and a highly clonal population structure. Evolutionary changes are mainly based on the acquisition of single nucleotide polymorphisms. However, the mode and speed of evolutionary processes in M. tuberculosis have not been defined so far. Here, the newly available high throughput sequencing technologies offer new perspectives to address this question.
BMBF
- German Center for Infection Research (DZIF) - Tuberculosis Translational Unit (TTU TB): Coordination site, infrastructure: Laboratory for Next Generation Sequencing (EpiMyc)
- TBseqDISK: molecular test based on Next Generation Sequencing for rapid diagnosis and comprehensive resistance determination in tuberculosis
- TB Sequel: Comorbidities, risk factors and longterm sequelae defining the individual outcome and public health impact of TB disease
BMG
- SeqMDRTB_NET: Network for application of sequencing technology for the fight against resistant tuberculosis in high incidence settings
- PHIMS-TB: German wide integrated molecular surveillance of TB
DFG
- Trans Evo: PhD programme for translational evolutionary research
FP7 ERANET Lac
- MDR-TBNet: Hostpathogen interactions in MultidrugResistant Tuberculosis (MDRTB): Study of the Molecular Epidemiology, Host Immune Responses and GenomeBased Prediction and Early Identification of MDRTB in High Tuberculosis Burden Settings
HORIZON 2020/European Developing Countries Clinical Trials Partnership (EDCTP)
- WANETAM: West Africa Network of Excellence for TB, AIDS and Malaria
- RaPaed-AIDA-TB: Rapid and Accurate Diagnosis of Paediatric TB - An AIDA (Assessment of Innovative Diagnostics and Algorithms for Early and Sensitive Detection of Acute TB) platform study
European Centre for Disease Prevention and Control (ECDC)
- EUseqMyTB: Pilot study on the use of Whole Genome Sequencing for molecular typing and characterization of tuberculosis in the EU/EEA
Innovative Medicines Initiative (IMI)
- ETBRA: European tuberculosis regimen accelerator: Characterization of new compounds active against TB
European Union
- CORVOS: Complement Regulation and Variations in opportunistic infections: Definition der Aufgabe des Komplementsystems für die TB Infektion unter Berücksichtigung der Stamm-Variation
- DRTB-HDT: stratifizierte Wirt-gerichtete Therapy der Medikamenten-resistenten Tuberkulose: eine randomisiert kontrollierte Multi-Center Studie
Wellcome Trust/ Bill&Melinda Gates Stiftung
- Cryptic/Wellcome Trust: Comprehensive Resistance Prediction for Tuberculosis: An International Consortium
Leibniz ScienceCampus
- EvoLUNG: Evolutionary Medicine of the Lung
Leibniz Center Infection
- Epigenetic consequences of Mtbc infection: Performance of infection experiments, RNAseq and methylome analysis
European and Developing Countries Clinical Trials Partnership (EDCTP)
- Core-NB: Collision of three global pandemics: the effect of tuberculosis and HIV on the epidemiological, clinical, virological and immunological trajectory of COVID-19 in Botswana and Namibia
Core-NB is an observational study supported by EDCTP and conducted by epidemiologists and researchers from Namibia, Botswana and Germany...
Drittmittel
European and Developing Countries Clinical Trials Partnership (EDCTP)
- Core-NB: Collision of three global pandemics: the effect of tuberculosis and HIV on the epidemiological, clinical, virological and immunological trajectory of COVID-19 in Botswana and Namibia
Core-NB is an observational study supported by EDCTP and conducted by epidemiologists and researchers from Namibia, Botswana and Germany.
Since February 2020, COVID-19 has become a global pandemic with unprecedented impact on public health and society in general. So far, most cases have occurred in high-income countries, and consequently, COVID-19 diagnostics and research have been established mainly in these countries. Looking at the global South, it becomes apparent that here Sars-Cov 2 meets already existing infectious diseases such as HIV and tuberculosis (TB). Both diseases themselves affect the immune systems of the patients and subsequently affect the immune response to further infection with other pathogens. The influence of HIV and tuberculosis on the course of COVID-19 disease is a particular gap in our knowledge. It is therefore important to understand how these three pandemics interact.
Core-NB brings together researchers from the University of Namibia (UNAM) with health experts from VICTUS GLOBAL BOTSWANA ORGANISATION (VGBO) and Health POVERTY ACTIONS (HPA). Both VGB and HPA are non-profit organisations (NGOs) working to improve lives through health promotion and economic empowerment. It is worth noting that VGBO was founded by women in Botswana, who also form the board of this organisation. The Research Center Borstel Leibniz Lung Center, as the coordinating institute, will not only be responsible for management and reporting, but will also offer training workshops to push capacity building in the partner countries.
The project includes two studies that will be conducted sequentially. The first study will follow the WHO protocol for household transmission investigations in the context of COVID-19. It will explore transmission frequency and describe the clinical spectrum of disease. Samples collected will also serve as basis for COVID-19 molecular epidemiology and host immunological response. The second study will evaluate the presentation, diagnosis and clinical characteristics of individuals presenting to sentinel health facilities in both countries. The project will have a strong laboratory strengthening component which will enhance COVID-19 laboratory and research capacity.
This will include the development of skills and knowledge for diagnostic testing and COVID-19 sequencing and will build scientific and research capacity. The findings from this project will provide robust data to assist in guiding national responses to COVID-19 in both countries as well as assisting with our understanding of the pathogenesis of the virus in the context of TB and HIV, in turn providing vital information on how to deliver clinical care and how to design therapeutics and vaccines.
Consortium
Research Center Borstel
Leibniz Lung Center
Prof. Dr. Stefan Niemann
www.fz-borstel.de
UNAM – UNIVERSITY OF NAMIBIA
Prof. Dr. Mareli Claassens
www.unam.edu.na
VICTUS GLOBAL BOTSWANA ORGANISATION
Dr. Chawanga Modongo
www.victusglobal.org
HEALTH POVERTY ACTION
Dr. Tadesse Kassaye Woldetsadik
www.healthpovertyaction.org
Management Team
Coordination
Prof. Dr. Stefan Niemann
Scientific Project Management
Dr. Christiane Gerlach
LINQ Management GmbH
www.linq-management.com
- Standardized culture systems for investigation of clinical M. tuberculosis complex isolates.
- Standardized methods for isolation of genomic DNA, RNA and intracellular protein.
- Molecular tools for analyses of genomic DNA and RNA (Agarose Gel Electrophoresis, Southern Blot, PCR, Real Time PCR, DNA-Sequencing, Microarray)
- Genotyping of M. tuberculosis complex isolates by:
- IS6110-DNA-Fingerprint
- Spoligotyping
- Mycobacterial Interspersed Repetitive Units Variable Number Repeats (MIRU-VNTR)-typing
- Analysis of Large Sequence Polymorphisms (Regions of Difference)
- Analysis of Single Nucleotide Polymorphisms (SNPs)
- Gene expression analysis of M. tuberculosis complex isolates by:
- Real-Time PCR
- Whole genome expression profiling
- Generation of M. tuberculosis mutants (S3)
- Bioinformatic analysis and storage of typing data by using the Bionumerics software
- Bioinformatic analysis of DNA sequence data by using different software packages (SeqScape, Lasergene, GenDB)
2024
Barilar, I, Fernando, T, Utpatel, C, Abujate, C, Madeira, CM, José, B, Mutaquiha, C, Kranzer, K, Niemann, T & Ismael, N et al. 2024, 'Emergence of bedaquiline-resistant tuberculosis and of multidrug-resistant and extensively drug-resistant Mycobacterium tuberculosis strains with rpoB Ile491Phe mutation not detected by Xpert MTB/RIF in Mozambique: a retrospective observational study', Lancet Infectious Diseases, Jg. 24, Nr. 3, S. 297-307. https://doi.org/10.1016/S1473-3099(23)00498-X
Blankson, HNA, Kamara, RF, Barilar, I, Andres, S, Conteh, OS, Dallenga, T, Foray, L, Maurer, F, Kranzer, K & Utpatel, C et al. 2024, 'Molecular determinants of multidrug-resistant tuberculosis in Sierra Leone', Microbiology spectrum, Jg. 12, Nr. 3, S. e0240523. https://doi.org/10.1128/spectrum.02405-23
CRyPTIC Consortium 2024, 'Quantitative drug susceptibility testing for Mycobacterium tuberculosis using unassembled sequencing data and machine learning', PLoS Computational Biology , Jg. 20, Nr. 8, S. e1012260. https://doi.org/10.1371/journal.pcbi.1012260
CRyPTIC Consortium 2024, 'Quantitative measurement of antibiotic resistance in Mycobacterium tuberculosis reveals genetic determinants of resistance and susceptibility in a target gene approach', Nature communications, Jg. 15, Nr. 1, S. 488. https://doi.org/10.1038/s41467-023-44325-5
Danchuk, SN, Solomon, OE, Kohl, TA, Dreyer, V, Barilar, I, Utpatel, C, Niemann, S, Soolingen, DV, Anthony, R & van Ingen, J et al. 2024, 'Challenging the gold standard: the limitations of molecular assays for detection of Mycobacterium tuberculosis heteroresistance', Thorax, Jg. 79, Nr. 7, S. 670-675. https://doi.org/10.1136/thorax-2023-220202
Diricks, M, Petersen, S, Bartels, L, Lâm, T-T, Claus, H, Bajanca-Lavado, MP, Hauswaldt, S, Stolze, R, Vázquez, OJ, Utpatel, C, Niemann, S, Rupp, J, Wohlers, I & Merker, M 2024, 'Revisiting mutational resistance to ampicillin and cefotaxime in Haemophilus influenzae', Genome medicine, Jg. 16, Nr. 1, S. 140. https://doi.org/10.1186/s13073-024-01406-4
Dreyer, V, Sonnenkalb, L, Diricks, M, Utpatel, C, Barilar, I, Mohr, V, Niemann, S, Kohl, TA & Merker, M 2024, 'Use of Whole Genome Sequencing for Mycobacterium tuberculosis Complex Antimicrobial Susceptibility Testing: From Sequence Data to Resistance Profiles', Methods in Molecular Biology, Jg. 2833, S. 195-210. https://doi.org/10.1007/978-1-0716-3981-8_18
Dyer, NP, Päuker, B, Baxter, L, Gupta, A, Bunk, B, Overmann, J, Diricks, M, Dreyer, V, Niemann, S, Holt, KE, Rahman, M, Brown, PE, Stark, R, Zhou, Z, Ott, S & Nübel, U 2024, 'EnteroBase in 2025: exploring the genomic epidemiology of bacterial pathogens', NUCLEIC ACIDS RESEARCH. https://doi.org/10.1093/nar/gkae902
Friesen, I, Dreyer, V, Klingmüller, A, Zuber, S, Hoffmann, AM, Suárez, I, Schütz, B, Preßel, T, Andres, S & Niemann, S et al. 2024, 'First detection of a Mycobacterium tuberculosis XDR clinical isolate harbouring an RpoB I491F mutation in a Ukrainian patient treated in Germany, October 2023', Eurosurveillance, Jg. 29, Nr. 28. https://doi.org/10.2807/1560-7917.ES.2024.29.28.2400420
Friesen, I, Saluzzo, F, Groenheit, R, Aubry, A, Anthony, R, Niemann, S, Mathys, V, Cirillo, DM & TB European Reference Laboratory Network (ERLTB-Net-3) 2024, 'Re: 'Availability of drugs and resistance testing for BPaLM regimen for rifampicin-resistant tuberculosis in Europe' by Lange et al', CLINICAL MICROBIOLOGY AND INFECTION , Jg. 30, Nr. 9, S. 1204-1206. https://doi.org/10.1016/j.cmi.2024.06.001
Germuskova, Z, Sosa, E, Lagos, AC, Aamot, HV, Beale, MA, Bertelli, C, Björkmann, J, Couto, N, Feige, L & Greub, G et al. 2024, 'Conference report: The first Bacterial Genome Sequencing Pan-European Network Conference', Microbes and Infection, S. 105410. https://doi.org/10.1016/j.micinf.2024.105410
Götz, MP, Duque Villegas, MA, Fageräng, B, Kerfin, A, Skjoedt, M-O, Garred, P & Rosbjerg, A 2024, 'Transient Binding Dynamics of Complement System Pattern Recognition Molecules on Pathogens', JOURNAL OF IMMUNOLOGY, Jg. 212, Nr. 9, S. 1493-1503. https://doi.org/10.4049/jimmunol.2300768
Gröschel, MI, Pérez-Llanos, FJ, Diel, R, Vargas, R, Escuyer, V, Musser, K, Trieu, L, Meissner, JS, Knorr, J & Klinkenberg, D et al. 2024, 'Differential rates of Mycobacterium tuberculosis transmission associate with host-pathogen sympatry', Nature Microbiology, Jg. 9, Nr. 8, S. 2113-2127. https://doi.org/10.1038/s41564-024-01758-y
Günther, G, Mhuulu, L, Diergaardt, A, Dreyer, V, Moses, M, Anyolo, K, Ruswa, N, Claassens, M, Niemann, S & Nepolo, E 2024, 'Bedaquiline Resistance after Effective Treatment of Multidrug-Resistant Tuberculosis, Namibia', EMERGING INFECTIOUS DISEASES, Jg. 30, Nr. 3, S. 568-571. https://doi.org/10.3201/eid3003.240134
Idris, R, Zielbauer, A-S, Koepsell, J, Kloka, J & Wetzstein, N 2024, 'Extracorporeal membrane oxygenation (ECMO) in patients with tuberculosis: systematic review and meta-analysis of 43 cases', BMC PULMONARY MEDICINE, Jg. 24, Nr. 1, S. 47. https://doi.org/10.1186/s12890-023-02715-x
Köser, CU, Miotto, P, Ismail, N, Anthony, RM, Utpatel, C, Merker, M, Niemann, S, Tahseen, S, Rigouts, L & Rodrigues, C et al. 2024, 'A composite reference standard is needed for bedaquiline antimicrobial susceptibility testing for Mycobacterium tuberculosis complex', The European respiratory journal, Jg. 64, Nr. 1. https://doi.org/10.1183/13993003.00391-2024
Larsson, L, Corbett, C, Kalmambetova, G, Utpatel, C, Ahmedov, S, Antonenka, U, Iskakova, A, Kadyrov, A, Kohl, TA & Barilar, V et al. 2024, 'Whole-genome sequencing drug susceptibility testing is associated with positive MDR-TB treatment response', INTERNATIONAL JOURNAL OF TUBERCULOSIS AND LUNG DISEASE, Jg. 28, Nr. 10, S. 494-499. https://doi.org/10.5588/ijtld.24.0052
Machado, E, Vasconcellos, S, Gomes, L, Catanho, M, Ramos, J, de Carvalho, L, Goldenberg, T, Redner, P, Caldas, P & Campos, C et al. 2024, 'Phylogenomic and genomic analysis reveals unique and shared genetic signatures of Mycobacterium kansasii complex species', Microbial genomics, Jg. 10, Nr. 7. https://doi.org/10.1099/mgen.0.001266
Meiwes, L, Kontsevaya, I, Chesov, D, Kulciţkaia, S, Dreyer, V, Hillemann, D, Dlamini, Q, Williams, C, Barer, M & Brinkmann, F et al. 2024, 'Whispers in the wind: Face mask sampling for Mycobacterium tuberculosis detection in children with pulmonary tuberculosis', JOURNAL OF INFECTIOUS DISEASES. https://doi.org/10.1093/infdis/jiae282
Mohr, V, Sonnenkalb, L, Utpatel, C, Barilar, I, Diricks, M, Dreyer, V, Niemann, S, Kohl, TA & Merker, M 2024, 'Use of Whole Genome Sequencing for Mycobacterium tuberculosis Complex Antimicrobial Susceptibility Testing', Methods in Molecular Biology, Jg. 2833, S. 185-193. https://doi.org/10.1007/978-1-0716-3981-8_17
Phelan, JE, Utpatel, C, Ismail, N, Cortes, T, Niemann, S, Cirillo, DM, Schön, T, Miotto, P & Köser, CU 2024, 'Careful classification of potential bedaquiline resistance mutations is critical when analysing their clinical impact', INTERNATIONAL JOURNAL OF TUBERCULOSIS AND LUNG DISEASE, Jg. 28, Nr. 6, S. 312-313. https://doi.org/10.5588/ijtld.24.0083
Rachwal, N, Idris, R, Dreyer, V, Richter, E, Wichelhaus, TA, Niemann, S, Wetzstein, N & Götsch, U 2024, 'Pathogen and host determinants of extrapulmonary tuberculosis among 1035 patients in Frankfurt am Main, Germany, 2008-2023', CLINICAL MICROBIOLOGY AND INFECTION . https://doi.org/10.1016/j.cmi.2024.11.009
Rupasinghe, P, Reenaers, R, Vereecken, J, Mulders, W, Cogneau, S, Merker, M, Niemann, S, Vally Omar, S, Rigouts, L & Köser, CU et al. 2024, 'Refined understanding of the impact of the Mycobacterium tuberculosis complex diversity on the intrinsic susceptibility to pretomanid', Microbiology spectrum, Jg. 12, Nr. 3, S. e0007024. https://doi.org/10.1128/spectrum.00070-24
Shavuka, O, Iipumbu, E, Boois, L, Günther, G, Hoddinott, G, Lin, H-H, Nepolo, E, Niemann, S, Ruswa, N & Seddon, J et al. 2024, 'Enhanced active case finding of drug-resistant tuberculosis in Namibia: a protocol for the hotspots, hospitals, and households (H3TB) study', BMJ open, Jg. 14, Nr. 2, S. e082665. https://doi.org/10.1136/bmjopen-2023-082665
Svensson, E, Ketelsen, H, Andres, S, Folkvardsen, DB, Hillemann, D, Conteh, O, Norman, A, Niemann, S, Lillebaek, T & Kuhns, M 2024, 'Dual-centre evaluation of the FluoroType MTBDR version 2 assay for detection of Mycobacterium tuberculosis complex and resistance-conferring mutations in pulmonary and extrapulmonary samples from Denmark, Germany and Sierra Leone', CLINICAL MICROBIOLOGY AND INFECTION , Jg. 30, Nr. 8, S. 1055-1060. https://doi.org/10.1016/j.cmi.2024.04.006
Utpatel, C, Zavaleta, M, Rojas-Bolivar, D, Mühlbach, A, Picoy, J, Portugal, W, Esteve-Solé, A, Alsina, L, Miotto, P & Bartholomeu, DC et al. 2024, 'Prison as a driver of recent transmissions of multidrug-resistant tuberculosis in Callao, Peru: a cross-sectional study', Lancet regional health. Americas, Jg. 31, S. 100674. https://doi.org/10.1016/j.lana.2024.100674
Wetzstein, N, Diricks, M, Andres, S, Kuhns, M, Marschall, L, Biciusca, T, Smaczny, C, Friesen, I, Niemann, S & Wichelhaus, TA 2024, 'Genomic diversity and clinical relevance of Mycobacterium simiae', ERJ Open Research, Jg. 10, Nr. 2, 00773-2023. https://doi.org/10.1183/23120541.00773-2023
Wetzstein, N, Diricks, M, Anton, TB, Andres, S, Kuhns, M, Kohl, TA, Schwarz, C, Lewin, A, Kehrmann, J & Kahl, BC et al. 2024, 'Clinical and genomic features of Mycobacterium avium complex: a multi-national European study', Genome medicine, Jg. 16, Nr. 1, S. 86. https://doi.org/10.1186/s13073-024-01359-8
2023
Baker, CR, Barilar, I, de Araujo, LS, Rimoin, AW, Parker, DM, Boyd, R, Tobias, JL, Moonan, PK, Click, ES, Finlay, A, Oeltmann, JE, Minin, VN, Modongo, C, Zetola, NM, Niemann, S & Shin, SS 2023, 'Use of High-Resolution Geospatial and Genomic Data to Characterize Recent Tuberculosis Transmission, Botswana', EMERGING INFECTIOUS DISEASES, Jg. 29, Nr. 5, S. 977-987. https://doi.org/10.3201/eid2905.220796
Botelho, J, Tüffers, L, Fuss, J, Buchholz, F, Utpatel, C, Klockgether, J, Niemann, S, Tümmler, B & Schulenburg, H 2023, 'Phylogroup-specific variation shapes the clustering of antimicrobial resistance genes and defence systems across regions of genome plasticity in Pseudomonas aeruginosa', EBioMedicine, Jg. 90, S. 104532. https://doi.org/10.1016/j.ebiom.2023.104532
Comprehensive Resistance Prediction for Tuberculosis: an International Consortium, Sonnenkalb, L, Carter, JJ, Spitaleri, A, Iqbal, Z, Hunt, M, Malone, KM, Utpatel, C, Cirillo, DM, Rodrigues, C, Nilgiriwala, KS, Fowler, PW, Merker, M & Niemann, S 2023, 'Bedaquiline and clofazimine resistance in Mycobacterium tuberculosis: an in-vitro and in-silico data analysis', The Lancet. Microbe, Jg. 4, Nr. 5, S. e358-e368. https://doi.org/10.1016/S2666-5247(23)00002-2
de Araujo, L, Cabibbe, AM, Mhuulu, L, Ruswa, N, Dreyer, V, Diergaardt, A, Günther, G, Claassens, M, Gerlach, C, Utpatel, C, Cirillo, DM, Nepolo, E & Niemann, S 2023, 'Implementation of targeted next-generation sequencing for the diagnosis of drug-resistant tuberculosis in low-resource settings: a programmatic model, challenges, and initial outcomes', Frontiers in public health, Jg. 11, S. 1204064. https://doi.org/10.3389/fpubh.2023.1204064
Diel, R, Meywald-Walther, K, Schwarzbach, C, Voss, K, Dreyer, V & Niemann, S 2023, 'Risk of tuberculosis transmission by children in Hamburg, Germany', RESPIRATORY MEDICINE , Jg. 209, S. 107152. https://doi.org/10.1016/j.rmed.2023.107152
ERA4TB consortium, van Wijk, RC, Lucía, A, Sudhakar, PK, Sonnenkalb, L, Gaudin, C, Hoffmann, E, Dremierre, B, Aguilar-Ayala, DA, Molin, MD, Rybniker, J, de Giorgi, S, Cioetto-Mazzabò, L, Segafreddo, G, Manganelli, R, Degiacomi, G, Recchia, D, Pasca, MR, Simonsson, USH & Ramón-García, S 2023, 'Implementing best practices on data generation and reporting of Mycobacterium tuberculosis in vitro assays within the ERA4TB consortium', iScience, Jg. 26, Nr. 4, S. 106411. https://doi.org/10.1016/j.isci.2023.106411
Gries, R, Dal Molin, M, Chhen, J, van Gumpel, E, Dreyer, V, Niemann, S & Rybniker, J 2023, 'Characterization of Two Novel Inhibitors of the Mycobacterium tuberculosis Cytochrome bc1 Complex', ANTIMICROBIAL AGENTS AND CHEMOTHERAPY, Jg. 67, Nr. 7, S. e0025123. https://doi.org/10.1128/aac.00251-23
Ismael, N, van Wyk, S, Tegally, H, Giandhari, J, San, JE, Moir, M, Pillay, S, Utpatel, C, Singh, L, Naidoo, Y, Ramphal, U, Mabunda, N, Abílio, N, Arnaldo, P, Xavier, J, Amoako, DG, Everatt, J, Ramphal, Y, Maharaj, A, de Araujo, L, Anyaneji, UJ, Tshiabuila, D, Viegas, S, Lessells, R, Engelbrecht, S, Gudo, E, Jani, I, Niemann, S, Wilkinson, E & de Oliveira, T 2023, 'Genomic epidemiology of SARS-CoV-2 during the first four waves in Mozambique', PLOS global public health, Jg. 3, Nr. 3, S. e0001593. https://doi.org/10.1371/journal.pgph.0001593
Koehler, N, Andres, S, Merker, M, Dreyer, V, John, A, Kuhns, M, Krieger, D, Choong, E, Verougstraete, N, Zur Wiesch, PA, Wicha, SG, König, C, Kalsdorf, B, Sanchez Carballo, PM, Schaub, D, Werngren, J, Schön, T, Peloquin, CA, Schönfeld, N, Verstraete, AG, Decosterd, LA, Aarnoutse, R, Niemann, S, Maurer, FP & Lange, C 2023, 'Pretomanid-Resistant Tuberculosis', Journal of infection, Jg. 86, Nr. 5, S. 520-524. https://doi.org/10.1016/j.jinf.2023.01.039
Pérez-Llanos, FJ, Dreyer, V, Barilar, I, Utpatel, C, Kohl, TA, Murcia, MI, Homolka, S, Merker, M & Niemann, S 2023, 'Transmission Dynamics of a Mycobacterium tuberculosis Complex Outbreak in an Indigenous Population in the Colombian Amazon Region', Microbiology spectrum, S. e0501322. https://doi.org/10.1128/spectrum.05013-22
Rollo, RF, Mori, G, Hill, TA, Hillemann, D, Niemann, S, Homolka, S, Fairlie, DP & Blumenthal, A 2023, 'Wollamide Cyclic Hexapeptides Synergize with Established and New Tuberculosis Antibiotics in Targeting Mycobacterium tuberculosis', Microbiology spectrum, Jg. 11, Nr. 4, S. e0046523. https://doi.org/10.1128/spectrum.00465-23
Smith, JP, Modongo, C, Oeltmann, JE, Dima, M, Matsiri, O, Fane, O, Molefi, T, Shin, SS, Barilar, I, Niemann, S, Zetola, NM & Moonan, PK 2023, 'High-Resolution Characterization of Nosocomial Mycobacterium tuberculosis Transmission Events in Botswana', American journal of epidemiology, Jg. 192, Nr. 3, S. 503-506. https://doi.org/10.1093/aje/kwac214
Tagliani, E, Kohl, TA, Ghodousi, A, Groenheit, R, Holicka, Y, Niemann, S, Maurer, FP, Cirillo, DM & Cambau, E 2023, 'Appeal from the European reference laboratory network for tuberculosis for improving the diagnosis of infections caused by non-tuberculous mycobacteria', CLINICAL MICROBIOLOGY AND INFECTION . https://doi.org/10.1016/j.cmi.2023.06.005
TBNET and RESIST-TB networks, Domínguez, J, Boeree, MJ, Cambau, E, Chesov, D, Conradie, F, Cox, V, Dheda, K, Dudnyk, A, Farhat, MR, Gagneux, S, Grobusch, MP, Gröschel, MI, Guglielmetti, L, Kontsevaya, I, Lange, B, van Leth, F, Lienhardt, C, Mandalakas, AM, Maurer, FP, Merker, M, Miotto, P, Molina-Moya, B, Morel, F, Niemann, S, Veziris, N, Whitelaw, A, Horsburgh, CR & Lange, C 2023, 'Clinical implications of molecular drug resistance testing for Mycobacterium tuberculosis: a 2023 TBnet/RESIST-TB consensus statement', Lancet Infectious Diseases, Jg. 23, Nr. 4, S. e122-e137. https://doi.org/10.1016/S1473-3099(22)00875-1
Trauth, J, Matt, U, Kohl, TA, Niemann, S & Herold, S 2023, 'Blind spot in endocarditis guidelines: Mycobacterium chimaera prosthetic valve endocarditis after cardiac surgery-a case series', European heart journal. Case reports, Jg. 7, Nr. 8, S. ytad400. https://doi.org/10.1093/ehjcr/ytad400
Wetzstein, N, Kohl, TA, Diricks, M, Mas-Peiro, S, Holubec, T, Kessel, J, Graf, C, Koch, B, Herrmann, E, Vehreschild, MJGT, Hogardt, M, Niemann, S, Stephan, C & Wichelhaus, TA 2023, 'Clinical characteristics and outcome of Mycobacterium chimaera infections after cardiac surgery: systematic review and meta-analysis of 180 heater-cooler unit associated cases', CLINICAL MICROBIOLOGY AND INFECTION , Jg. 29, Nr. 8, S. 1008-1014. https://doi.org/10.1016/j.cmi.2023.03.005
Zwyer, M, Rutaihwa, LK, Windels, E, Hella, J, Menardo, F, Sasamalo, M, Sommer, G, Schmülling, L, Borrell, S, Reinhard, M, Dötsch, A, Hiza, H, Stritt, C, Sikalengo, G, Fenner, L, De Jong, BC, Kato-Maeda, M, Jugheli, L, Ernst, JD, Niemann, S, Jeljeli, L, Ballif, M, Egger, M, Rakotosamimanana, N, Yeboah-Manu, D, Asare, P, Malla, B, Dou, HY, Zetola, N, Wilkinson, RJ, Cox, H, Carter, EJ, Gnokoro, J, Yotebieng, M, Gotuzzo, E, Abimiku, A, Avihingsanon, A, Xu, ZM, Fellay, J, Portevin, D, Reither, K, Stadler, T, Gagneux, S & Brites, D 2023, 'Back-to-Africa introductions of Mycobacterium tuberculosis as the main cause of tuberculosis in Dar es Salaam, Tanzania', PLOS PATHOGENS, Jg. 19, Nr. 4, S. e1010893. https://doi.org/10.1371/journal.ppat.1010893
2022
Abdul, JBPAA, Adegbite, BR, Ndanga, MED, Edoa, JR, Mevyann, RC, Mfoumbi, GRAI, de Dieu, TJ, Mahoumbou, J, Biyogho, CM, Jeyaraj, S, Niemann, S, Lell, B, Kremsner, PG, Alabi, AS, Adegnika, AA & Grobusch, MP 2022, 'Resistance patterns among drug-resistant tuberculosis patients and trends-over-time analysis of national surveillance data in Gabon, Central Africa', Infection, S. 1-8. https://doi.org/10.1007/s15010-022-01941-5
Akwani, WC, van Vliet, AHM, Joel, JO, Andres, S, Diricks, M, Maurer, FP, Chambers, MA & Hingley-Wilson, SM 2022, 'The Use of Comparative Genomic Analysis for the Development of Subspecies-Specific PCR Assays for Mycobacterium abscessus', Frontiers in Cellular and Infection Microbiology, Jg. 12, S. 816615. https://doi.org/10.3389/fcimb.2022.816615
Antimycobacterial Susceptibility Testing Group 2022, 'Updating the approaches to define susceptibility and resistance to anti-tuberculosis agents: implications for diagnosis and treatment', The European respiratory journal, Jg. 59, Nr. 4, 2200166. https://doi.org/10.1183/13993003.00166-2022
Bateson, A, Ortiz Canseco, J, McHugh, TD, Witney, AA, Feuerriegel, S, Merker, M, Kohl, TA, Utpatel, C, Niemann, S, Andres, S, Kranzer, K, Maurer, FP, Ghodousi, A, Borroni, E, Cirillo, DM, Wijkander, M, Toro, JC, Groenheit, R, Werngren, J, Machado, D, Viveiros, M, Warren, RM, Sirgel, F, Dippenaar, A, Köser, CU, Sun, E & Timm, J 2022, 'Ancient and recent differences in the intrinsic susceptibility of Mycobacterium tuberculosis complex to pretomanid', JOURNAL OF ANTIMICROBIAL CHEMOTHERAPY, Jg. 77, Nr. 6, S. 1685-1693. https://doi.org/10.1093/jac/dkac070
Brandenburg, J, Heyckendorf, J, Marwitz, F, Zehethofer, N, Linnemann, L, Gisch, N, Karaköse, H, Reimann, M, Kranzer, K, Kalsdorf, B, Sanchez-Carballo, P, Weinkauf, M, Scholz, V, Malm, S, Homolka, S, Gaede, KI, Herzmann, C, Schaible, UE, Hölscher, C, Reiling, N & Schwudke, D 2022, 'Tuberculostearic Acid-Containing Phosphatidylinositols as Markers of Bacterial Burden in Tuberculosis', ACS infectious diseases, Jg. 8, Nr. 7, S. 1303-1315. https://doi.org/10.1021/acsinfecdis.2c00075
Chesov, E, Chesov, D, Maurer, FP, Andres, S, Utpatel, C, Barilar, I, Donica, A, Reimann, M, Niemann, S, Lange, C, Crudu, V, Heyckendorf, J & Merker, M 2022, 'Emergence of bedaquiline resistance in a high tuberculosis burden country', The European respiratory journal, Jg. 59, Nr. 3, 2100621. https://doi.org/10.1183/13993003.00621-2021
Claassens, M, Dreyer, V, Nepolo, E, Mokomele, Q, van Rooyen, G, Ruswa, N, Günther, G & Niemann, S 2022, 'Whole-Genome Sequencing for Resistance Prediction and Transmission Analysis of Mycobacterium tuberculosis Complex Strains from Namibia', Microbiology spectrum, Jg. 10, Nr. 5, S. e0158622. https://doi.org/10.1128/spectrum.01586-22
CRyPTIC Consortium 2022, 'A data compendium associating the genomes of 12,289 Mycobacterium tuberculosis isolates with quantitative resistance phenotypes to 13 antibiotics', PLOS BIOLOGY , Jg. 20, Nr. 8, S. e3001721. https://doi.org/10.1371/journal.pbio.3001721
CRyPTIC Consortium 2022, 'High fluoroquinolone resistance proportions among multidrug-resistant tuberculosis driven by dominant L2 Mycobacterium tuberculosis clones in the Mumbai Metropolitan Region', Genome medicine, Jg. 14, Nr. 1, S. 95. https://doi.org/10.1186/s13073-022-01076-0
CRyPTIC Consortium, Barilar, I, Dreyer, V, Kohl, T, Merker, M, Niemann, S & Utpatel, C 2022, 'The 2021 WHO catalogue of Mycobacterium tuberculosis complex mutations associated with drug resistance: A genotypic analysis', The Lancet. Microbe, Jg. 3, Nr. 4, S. e265-e273. https://doi.org/10.1016/S2666-5247(21)00301-3
CRyPTIC Consortium, Niemann, S, Barilar, I, Dreyer, V, Merker, M, Kohl, T & Utpatel, C 2022, 'Epidemiological cutoff values for a 96-well broth microdilution plate for high-throughput research antibiotic susceptibility testing of M. tuberculosis', The European respiratory journal, Jg. 60, Nr. 4, 2200239. https://doi.org/10.1183/13993003.00239-2022
Diricks, M, Kohl, TA, Käding, N, Leshchinskiy, V, Hauswaldt, S, Jiménez Vázquez, O, Utpatel, C, Niemann, S, Rupp, J & Merker, M 2022, 'Whole genome sequencing-based classification of human-related Haemophilus species and detection of antimicrobial resistance genes', Genome medicine, Jg. 14, Nr. 1, S. 13. https://doi.org/10.1186/s13073-022-01017-x
Diricks, M, Merker, M, Wetzstein, N, Kohl, TA, Niemann, S & Maurer, FP 2022, 'Delineating Mycobacterium abscessus population structure and transmission employing high-resolution core genome multilocus sequence typing', Nature communications, Jg. 13, Nr. 1, S. 4936. https://doi.org/10.1038/s41467-022-32122-5
European Laboratory Initiative on TB, HIV and Viral Hepatitis(3) & Niemann, S 2022, 'Diagnostic Capacities for Multidrug-Resistant Tuberculosis in the World Health Organization European Region: Action is Needed by all Member States', Journal of Molecular Diagnostics, Jg. 24, Nr. 11, S. 1189-1194. https://doi.org/10.1016/j.jmoldx.2022.07.005
Finci, I, Albertini, A, Merker, M, Andres, S, Bablishvili, N, Barilar, I, Cáceres, T, Crudu, V, Gotuzzo, E, Hapeela, N, Hoffmann, H, Hoogland, C, Kohl, TA, Kranzer, K, Mantsoki, A, Maurer, FP, Nicol, MP, Noroc, E, Plesnik, S, Rodwell, T, Ruhwald, M, Savidge, T, Salfinger, M, Streicher, E, Tukvadze, N, Warren, R, Zemanay, W, Zurek, A, Niemann, S & Denkinger, CM 2022, 'Investigating resistance in clinical Mycobacterium tuberculosis complex isolates with genomic and phenotypic antimicrobial susceptibility testing: a multicentre observational study', The Lancet. Microbe, Jg. 3, Nr. 9, S. e672-e682. https://doi.org/10.1016/S2666-5247(22)00116-1
Gisch, N, Utpatel, C, Gronbach, LM, Kohl, TA, Schombel, U, Malm, S, Dobos, KM, Hesser, DC, Diel, R, Götsch, U, Gerdes, S, Shuaib, YA, Ntinginya, NE, Khosa, C, Viegas, S, Kerubo, G, Ali, S, Al-Hajoj, SA, Ndung’u, PW, Rachow, A, Hoelscher, M, Maurer, FP, Schwudke, D, Niemann, S, Reiling, N & Homolka, S 2022, 'Sub-Lineage Specific Phenolic Glycolipid Patterns in the Mycobacterium tuberculosis Complex Lineage 1', Frontiers in Microbiology, Jg. 13, S. 832054. https://www.frontiersin.org/article/10.3389/fmicb.2022.832054
Goldstein, IH, Bayer, D, Barilar, I, Kizito, B, Matsiri, O, Modongo, C, Zetola, NM, Niemann, S, Minin, VM & Shin, SS 2022, 'Using genetic data to identify transmission risk factors: Statistical assessment and application to tuberculosis transmission', PLoS Computational Biology , Jg. 18, Nr. 12, S. e1010696. https://doi.org/10.1371/journal.pcbi.1010696
Große, C, Kohl, TA, Niemann, S, Herzberg, M & Nies, DH 2022, 'Loss of mobile genomic islands in metal resistant, hydrogen-oxidizing Cupriavidus metallidurans', APPLIED AND ENVIRONMENTAL MICROBIOLOGY , Jg. 88, Nr. 4, S. e0204821. https://doi.org/10.1128/AEM.02048-21
Hansen, J, Kolbe, K, König, IR, Scherließ, R, Hellfritzsch, M, Malm, S, Müller-Loennies, S, Zallet, J, Hillemann, D, Wiesmüller, K-H, Herzmann, C, Brandenburg, J & Reiling, N 2022, 'Lipobiotin-capture magnetic bead assay for isolation, enrichment and detection of Mycobacterium tuberculosis from saliva', PLOS ONE, Jg. 17, Nr. 7, S. e0265554. https://doi.org/10.1371/journal.pone.0265554
Kerubo, G, Ndungu, P, Shuaib, YA, Amukoye, E, Revathi, G, Homolka, S, Kariuki, S, Merker, M & Niemann, S 2022, 'Molecular Epidemiology of Mycobacterium tuberculosis Complex Strains in Urban and Slum Settings of Nairobi, Kenya', Genes, Jg. 13, Nr. 3, 475. https://doi.org/10.3390/genes13030475
Klein, C, Borsche, M, Balck, A, Föh, B, Rahmöller, J, Peters, E, Knickmann, J, Lane, M, Vollstedt, E-J, Elsner, SA, Käding, N, Hauswaldt, S, Lange, T, Hundt, JE, Lehrian, S, Giese, J, Mischnik, A, Niemann, S, Maurer, F, Homolka, S, Paulowski, L, Kramer, J, Twesten, C, Sina, C, Gillessen-Kaesbach, G, Busch, H, Ehlers, M, Taube, S, Rupp, J & Katalinic, A 2022, 'One-year surveillance of SARS-CoV-2 transmission of the ELISA cohort: A model for population-based monitoring of infection risk', Science advances, Jg. 8, Nr. 15, S. eabm5016. https://doi.org/10.1126/sciadv.abm5016
Mbelele, PM, Utpatel, C, Sauli, E, Mpolya, EA, Mutayoba, BK, Barilar, I, Dreyer, V, Merker, M, Sariko, ML, Swema, BM, Mmbaga, BT, Gratz, J, Addo, KK, Pletschette, M, Niemann, S, Houpt, ER, Mpagama, SG & Heysell, SK 2022, 'Whole genome sequencing-based drug resistance predictions of multidrug-resistant Mycobacterium tuberculosis isolates from Tanzania', JAC-antimicrobial resistance, Jg. 4, Nr. 2, S. dlac042. https://doi.org/10.1093/jacamr/dlac042
Merker, M, Rasigade, J-P, Barbier, M, Cox, H, Feuerriegel, S, Kohl, TA, Shitikov, E, Klaos, K, Gaudin, C, Antoine, R, Diel, R, Borrell, S, Gagneux, S, Nikolayevskyy, V, Andres, S, Crudu, V, Supply, P, Niemann, S & Wirth, T 2022, 'Transcontinental spread and evolution of Mycobacterium tuberculosis W148 European/Russian clade toward extensively drug resistant tuberculosis', Nature communications, Jg. 13, Nr. 1, S. 5105. https://doi.org/10.1038/s41467-022-32455-1
Mesfin, EA, Merker, M, Beyene, D, Tesfaye, A, Shuaib, YA, Addise, D, Tessema, B & Niemann, S 2022, 'Prediction of drug resistance by Sanger sequencing of Mycobacterium tuberculosis complex strains isolated from multidrug resistant tuberculosis suspect patients in Ethiopia', PLOS ONE, Jg. 17, Nr. 8, S. e0271508. https://doi.org/10.1371/journal.pone.0271508
Rachow, A, Saathoff, E, Mindru, R, Popescu, O, Lugoji, D, Mahler, B, Merker, M, Niemann, S, Olaru, ID, Kastner, S, Hoelscher, M, Lange, C & Ibraim, E 2022, 'Diagnostic performance of the AID line probe assay in the detection of Mycobacterium tuberculosis and drug resistance in Romanian patients with presumed TB', PLOS ONE, Jg. 17, Nr. 8, S. e0271297. https://doi.org/10.1371/journal.pone.0271297
Shuaib, YA, Utpatel, C, Kohl, TA, Barilar, I, Diricks, M, Ashraf, N, Wieler, LH, Kerubo, G, Mesfin, EA, Diallo, AB, Al-Hajoj, S, Ndung'u, P, Fitzgibbon, MM, Vaziri, F, Sintchenko, V, Martinez, E, Viegas, SO, Zhou, Y, Azmy, A, Al-Amry, K, Godreuil, S, Varma-Basil, M, Narang, A, Ali, S, Beckert, P, Dreyer, V, Kabwe, M, Bates, M, Hoelscher, M, Rachow, A, Gori, A, Tekwu, EM, Sidze, LK, Jean-Paul, AA, Beng, VP, Ntoumi, F, Frank, M, Diallo, AG, Mboup, S, Tessema, B, Beyene, D, Khan, SN, Diel, R, Supply, P, Maurer, FP, Hoffmann, H, Niemann, S & Merker, M 2022, 'Origin and Global Expansion of Mycobacterium tuberculosis Complex Lineage 3', Genes, Jg. 13, Nr. 6, 990. https://doi.org/10.3390/genes13060990
Sibandze, DB, Kay, A, Dreyer, V, Sikhondze, W, Dlamini, Q, DiNardo, A, Mtetwa, G, Lukhele, B, Vambe, D, Lange, C, Glenn Dlamini, M, Ness, T, Mejia, R, Kalsdorf, B, Heyckendorf, J, Kuhns, M, Maurer, FP, Dlamini, S, Maphalala, G, Niemann, S & Mandalakas, A 2022, 'Rapid molecular diagnostics of tuberculosis resistance by targeted stool sequencing', Genome medicine, Jg. 14, Nr. 1, S. 52. https://doi.org/10.1186/s13073-022-01054-6
The CRyPTIC Consortium & Niemann, S 2022, 'Genome-wide association studies of global Mycobacterium tuberculosis resistance to 13 antimicrobials in 10,228 genomes identify new resistance mechanisms', PLOS BIOLOGY , Jg. 20, Nr. 8, S. e3001755. https://doi.org/10.1371/journal.pbio.3001755
Wetzstein, N, Diricks, M, Kohl, TA, Wichelhaus, TA, Andres, S, Paulowski, L, Schwarz, C, Lewin, A, Kehrmann, J, Kahl, BC, Dichtl, K, Hügel, C, Eickmeier, O, Smaczny, C, Schmidt, A, Zimmermann, S, Nährlich, L, Hafkemeyer, S, Niemann, S, Maurer, FP & Hogardt, M 2022, 'Molecular Epidemiology of Mycobacterium abscessus Isolates Recovered from German Cystic Fibrosis Patients', Microbiology spectrum, Jg. 10, Nr. 4, S. e0171422. https://doi.org/10.1128/spectrum.01714-22
Zooniverse Volunteer Community & Niemann, S 2022, 'A crowd of BashTheBug volunteers reproducibly and accurately measure the minimum inhibitory concentrations of 13 antitubercular drugs from photographs of 96-well broth microdilution plates', eLife, Jg. 11, e75046. https://doi.org/10.7554/eLife.75046
Head
Scientific Project Management
Scientific staff
Campus Charité Mitte (CCM) and Campus Virchow-Klinikum (CVK)
Charité – Universitätsmedizin Berlin
Charitéplatz 1, 10117 Berlin
Theodor-Stern-Kai 7, 60590 Frankfurt/Main, Germany
Technical staff
