Evolution of the Resistome
Main Emphasis
The global rise of antimicrobial resistance (AMR) is a public health crisis. The human microbiome and all associated resistance genes ("the resistome") are under constant evolutionary pressure. Disease, treatment, microbiome cross-talk, and the host immune system can change the composition of host microbes ("dysbiosis") or select for antimicrobial resistances. We employ laboratory evolution experiments and microbial genomics, such as whole (meta)genome sequencing, to understand bacterial evolutionary pathways that influence disease progression or treatment outcomes. In the long run, we seek to identify improved therapies which reduce or prevent pathogen adaptation, e.g. resistance evolution, and preserve a healthy microbiome.
We are particularly interested in the changes of the microbiome composition in patients treated for tuberculosis, or other lung infections as well as bronchial carcinoma. Therefore, we analyze within the Schleswig-Holstein Excellence Cluster "Precision Medicine in chronic Inflammation" (PMI) the microbiome of stool and bronchoscopy specimens. Furthermore, we sought to identify and isolate key bacterial species which potentially influence therapy outcomes.
In the near future we plan evolutionary experiments to analyze the adaptation of lung pathogens especially under therapy conditions. Are there possibly therapeutic interventions which can stall or reverse antibiotic resistance evolution?
EXC2167 PMI Mini-Proposal:
"Analysis of the gut and lung microbiome in bacterial infections and inflammatory diseases of the lower respiratory tract"
- 16s rRNA sequencing
- Whole metagenome sequencing
- Whole genome sequencing
- Evolutionary Genomics
2024
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