Evolution of the Resistome

The rise of antimicrobial resistant (AMR) bacteria is a threat to global health. We investigate the evolution of resistance-associated genes (“the resistome”), for example, under therapeutic conditions, and collateral effects that may arise. Genetic changes in pathogens and their interactions with the microbiome can influence the effectiveness and success of a therapy. In this context, we use in vitro evolution experiments and microbial genome analyses to understand evolutionary adaptations of pathogens and the microbiome. Our goal is to use this knowledge to develop innovative therapeutic strategies that reduce AMR evolution in chronic lung diseases.
- Evolution of beta-lactam resistance in Haemophilus influenzae
- Studies on the lung and gut microbiome in drug resistant and drug susceptible tuberculosis patients
- Identification of biomarkers in the microbiome of COVID-19 patients
- Strain-specific effects in pathogen-microbiome-host Interactions
GHPP BMG9 (2024)
“Nasopharyngeal microbiomes of patients with suspected SARS-CoV2 infection”
EXC2167 PMI Mini-Proposal (2021)
“Analysis of the gut and lung microbiome in bacterial infections and inflammatory diseases of the lower respiratory tract”
- 16S rRNA sequencing
- Whole metagenome analysis
- Bacterial whole genome analysis
- Population genomic analysis
- Air liquid interface model with airway epithelial cells
2025
Boutin, S, Käding, N, Belheouane, M, Merker, M, Rupp, J & Nurjadi, D 2025, 'Towards unraveling antimicrobial resistance dynamics: a longitudinal exploration of rectal swab metagenomes', BMC MICROBIOLOGY, Jg. 25, Nr. 1, S. 150. https://doi.org/10.1186/s12866-025-03874-z
Diricks, M, Maurer, FP, Dreyer, V, Barilar, I, Utpatel, C, Merker, M, Wetzstein, N & Niemann, S 2025, 'Genomic insights into the plasmidome of non-tuberculous mycobacteria', Genome medicine, Jg. 17, Nr. 1, S. 19. https://doi.org/10.1186/s13073-025-01443-7
Krysenko, S, Emani, CS, Bäuerle, M, Oswald, M, Kulik, A, Meyners, C, Hillemann, D, Merker, M, Prosser, G, Wohlers, I, Hausch, F, Brötz-Oesterhelt, H, Mitulski, A, Reiling, N & Wohlleben, W 2025, 'GlnA3Mt is able to glutamylate spermine but it is not essential for the detoxification of spermine in Mycobacterium tuberculosis', JOURNAL OF BACTERIOLOGY, S. e0043924. https://doi.org/10.1128/jb.00439-24
2024
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
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
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
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
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
2023
Belheouane, M, Hermes, BM, Van Beek, N, Benoit, S, Bernard, P, Drenovska, K, Gerdes, S, Gläser, R, Goebeler, M, Günther, C, von Georg, A, Hammers, CM, Holtsche, MM, Homey, B, Horváth, ON, Hübner, F, Linnemann, B, Joly, P, Márton, D, Patsatsi, A, Pföhler, C, Sárdy, M, Huilaja, L, Vassileva, S, Zillikens, D, Ibrahim, S, Sadik, CD, Schmidt, E & Baines, JF 2023, 'Characterization of the skin microbiota in bullous pemphigoid patients and controls reveals novel microbial indicators of disease', Journal of advanced research, Jg. 44, S. 71-79. https://doi.org/10.1016/j.jare.2022.03.019
Chung, CJ, Hermes, BM, Gupta, Y, Ibrahim, S, Belheouane, M & Baines, JF 2023, 'Genome-wide mapping of gene-microbe interactions in the murine lung microbiota based on quantitative microbial profiling', Animal microbiome, Jg. 5, Nr. 1, S. 31. https://doi.org/10.1186/s42523-023-00250-y
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
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
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
2022
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
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
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, 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
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
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
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
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
Head

Scientific staff


Technical staff


Alumni
- Jeniffer Asiimwe
- Xènia Camprubí Márquez
- Elina Guzmann