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Evolution of the Resistome

Prof. Dr. Matthias Merker
Prof. Dr. Matthias Merker
+49 4537 / 188-7570
+49 4537 / 188-3110
This email address is being protected from spambots. You need JavaScript enabled to view it.

 

We study how antimicrobial resistance (AMR) emerges, evolves, and shapes the biology of bacterial pathogens and their microbial communities. Our work focuses on genetic adaptations, evolutionary trade-offs, and mechanistic interactions between respiratory pathogens and the microbiome.

By combining whole genome and metagenome analyses with experimental evolution and host-cell models, we investigate how resistant bacterial populations are selected and what collateral effects arise in the process. We hypothesize that the genetic background of individual strains and their unique adaptive and exposure history can give rise to unexpected, yet largely unexplored phenotypes. These strain-specific differences influence virulence, antibiotic susceptibility, and microbial interactions, offering new perspectives for predicting disease outcomes and therapeutic success.

Our goal is to uncover the underlying evolutionary principles of resistance development and their consequences, and to translate this knowledge into strategies that limit pathogen adaptation and enable sustainable antimicrobial therapies.

 

  • Evolution of beta-lactam resistance in Haemophilus influenzae
  • Studies on the lung and gut microbiome in tuberculosis patients
  • Exploring microbiome signatures of the upper respiratory tract as biomarker for lung health
  • Strain-specific effects and microbial interactions in an epithelial cell model

 

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 / ITS amplicon sequencing
  • Whole metagenome analysis
  • Bacterial whole genome analysis
  • Population genomic analysis
  • Air liquid interface model with airway epithelial cells
  • Microbial co-culture model (iron limited conditions)

2025

Belheouane, M, Kalsdorf, B, Niemann, S, Gaede, KI, Lange, C, Heyckendorf, J & Merker, M 2025, 'Serratia sp. traits distinguish the lung microbiome of patients with tuberculosis and non-tuberculous mycobacterial lung diseases', PLOS ONE, Jg. 20, Nr. 6, S. e0325362. https://doi.org/10.1371/journal.pone.0325362

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

Petersen, S, Diricks, M, Utpatel, C, Schulenburg, H & Merker, M 2025, 'A novel mechanism of unstable heteroresistance via reversible ompP2 mutations in Haemophilus influenzae', INTERNATIONAL JOURNAL OF INFECTIOUS DISEASES , Jg. 161, S. 108178. https://doi.org/10.1016/j.ijid.2025.108178

Petersen, S, Diricks, M, Utpatel, C, Schulenburg, H & Merker, M 2025, 'Evolution of beta-lactam resistance causes fitness reductions and several cases of collateral sensitivities in the human pathogen Haemophilus influenzae', ANTIMICROBIAL AGENTS AND CHEMOTHERAPY, S. e0057625. https://doi.org/10.1128/aac.00576-25

Protic, D, Bascarevic, D, Dimitrijevic, S, Pesovic, J, Nikolic, V, Nikolic, S, Novicevic, V, Markovic, J, Arandjelovic, I, Savic-Pavicevic, D, Diricks, M, Belheouane, M & Merker, M 2025, 'Microbiome modulation and behavioural improvements in children with fragile X syndrome following probiotic intake: A pilot study', Scientific Reports. https://doi.org/10.1038/s41598-025-29896-1

Rößler, S, Boutin, S, Berner, R, Tomidis Chatzimanouil, MK, Belheouane, M, Rupp, J, Merker, M, Dresden GAS Study Group, Töpfner, N & Nurjadi, D 2025, 'Evidence for early circulation of the M1UK sublineage of Streptococcus pyogenes in Germany, 2015-2023', Emerging microbes & infections, Jg. 14, Nr. 1, S. 2576587. https://doi.org/10.1080/22221751.2025.2576587

Sonnenkalb, L, Trubenová, B, Regoes, RR, Merker, M & Niemann, S 2025, 'The mutant selection window of moxifloxacin and bedaquiline resistant Mycobacterium tuberculosis', Journal of infection, S. 106523. https://doi.org/10.1016/j.jinf.2025.106523

 

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

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

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

Chesov, E, Chesov, D, Reimann, M, Dreyer, V, Utpatel, C, Gröschel, MI, Ciobanu, N, Crudu, V, Lange, C, Heyckendorf, J & Merker, M 2023, 'Impact of Mycobacterium tuberculosis strain type on multidrug-resistant tuberculosis severity, Republic of Moldova', Journal of infection, Jg. 87, Nr. 6, S. 588-591. https://doi.org/10.1016/j.jinf.2023.10.001

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

Economou Lundeberg, E, Andersson, V, Wijkander, M, Groenheit, R, Mansjö, M, Werngren, J, Cortes, T, Barilar, I, Niemann, S, Merker, M, Köser, CU & Davies Forsman, L 2023, 'In vitro activity of new combinations of β-lactam and β-lactamase inhibitors against the Mycobacterium tuberculosis complex', Microbiology spectrum, Jg. 11, Nr. 5, S. e0178123. https://doi.org/10.1128/spectrum.01781-23

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

Noroc, E, Chesov, D, Merker, M, Gröschel, MI, Barilar, I, Dreyer, V, Ciobanu, N, Reimann, M, Crudu, V & Lange, C 2023, 'Limited Nosocomial Transmission of Drug-Resistant Tuberculosis, Moldova', EMERGING INFECTIOUS DISEASES, Jg. 29, Nr. 5, S. 1046-1050. https://doi.org/10.3201/eid2905.230035

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

Schlanderer, J, Hoffmann, H, Lüddecke, J, Golubov, A, Grasse, W, Kindler, EV, Kohl, TA, Merker, M, Metzger, C, Mohr, V, Niemann, S, Pilloni, C, Plesnik, S, Raya, B, Shresta, B, Utpatel, C, Zengerle, R, Beutler, M & Paust, N 2023, 'Two-stage tuberculosis diagnostics: combining centrifugal microfluidics to detect TB infection and Inh and Rif resistance at the point of care with subsequent antibiotic resistance profiling by targeted NGS', Lab on a chip, Jg. 24, Nr. 1, S. 74-84. https://doi.org/10.1039/d3lc00783a

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, 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

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

Fowler, PW, Wright, C, Spiers, H, Zhu, T, Baeten, EML, Hoosdally, SW, Gibertoni Cruz, AL, Roohi, A, Kouchaki, S, Walker, TM, Peto, TEA, Miller, G, Lintott, C, Clifton, D, Crook, DW, Walker, AS, Zooniverse Volunteer Community & The CRyPTIC Consortium 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

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

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

The CRyPTIC Consortium, 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

 

Head

Prof. Dr. Matthias Merker
Prof. Dr. Matthias Merker
+49 4537 / 188-7570
+49 4537 / 188-3110
This email address is being protected from spambots. You need JavaScript enabled to view it.

 

Scientific staff

Nurper Alacatli
Nurper Alacatli
Doktorandin
This email address is being protected from spambots. You need JavaScript enabled to view it.
Dr. Meriem Belheouane
Dr. Meriem Belheouane
Stellvertretung / Deputy
+49 4537 / 188-7550
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Technical staff

Dörte Grella
Dörte Grella
+49 4537 / 188-3200
+49 4537 / 188-7450
This email address is being protected from spambots. You need JavaScript enabled to view it.
Anja Lüdemann
Anja Lüdemann
+49 4537 / 188-7638
+49 4537 / 188-3110
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Alumni

  • Jeniffer Asiimwe
  • Xènia Camprubí Márquez
  • Elina Guzmann
  • Lea Jäger
  • Loide Ngolombe
  • Sabine Petersen
  • Tim Studt

 

Last Update: 24.11.2025