REAL

Characterization of antibiotic resistomes by reprogrammed bacteriophage-enabled functional metagenomics in clinical strains

Apjok, Gábor and Számel, Mónika and Christodoulou, Chryso and Seregi, Viktória and Vásárhelyi, Bálint Márk and Stirling, Tamás and Eszenyi, Bálint and Sári, Tóbiás and Vidovics, Fanni and Nagrand, Erika and Kovács, Dorina and Szili, Petra and Lantos, Ildikó Ilona and Méhi, Orsolya Katinka and Jangir, Pramod Kumar and Herczeg, Róbert and Gálik, Bence and Urbán, Péter and Gyenesei, Attila and Draskovits, Gábor and Nyerges, Ákos and Fekete, Gergely and Bodai, László and Zsindely, Nóra and Dénes, Béla and Yosef, Ido and Qimron, Udi and Papp, Balázs and Pál, Csaba and Kintses, Bálint (2023) Characterization of antibiotic resistomes by reprogrammed bacteriophage-enabled functional metagenomics in clinical strains. NATURE MICROBIOLOGY, 8 (3). pp. 410-423. ISSN 2058-5276

[img]
Preview
Text
s41564-023-01320-2.pdf - Published Version

Download (5MB) | Preview

Abstract

Functional metagenomics is a powerful experimental tool to identify antibiotic resistance genes (ARGs) in the environment, but the range of suitable host bacterial species is limited. This limitation affects both the scope of the identified ARGs and the interpretation of their clinical relevance. Here we present a functional metagenomics pipeline called Reprogrammed Bacteriophage Particle Assisted Multi-species Functional Metagenomics (DEEPMINE). This approach combines and improves the use of T7 bacteriophage with exchanged tail fibres and targeted mutagenesis to expand phage host-specificity and efficiency for functional metagenomics. These modified phage particles were used to introduce large metagenomic plasmid libraries into clinically relevant bacterial pathogens. By screening for ARGs in soil and gut microbiomes and clinical genomes against 13 antibiotics, we demonstrate that this approach substantially expands the list of identified ARGs. Many ARGs have species-specific effects on resistance; they provide a high level of resistance in one bacterial species but yield very limited resistance in a related species. Finally, we identified mobile ARGs against antibiotics that are currently under clinical development or have recently been approved. Overall, DEEPMINE expands the functional metagenomics toolbox for studying microbial communities.

Item Type: Article
Additional Information: Funding Agency and Grant Number: National Laboratory of Biotechnology Grants [NKFIH-871-3/2020, 2022-2.1.1-NL-2022-00008]; European Union [754432]; European Research Council [648364, 862077]; National Research, Development and Innovation Office grant [FK-135245, FK-124254]; National Research, Development and Innovation Office; Ministry for Innovation and Technology [KKP 129814, 126506]; New National Excellence Program of the Ministry of Human Capacities [UNKP-20-5-SZTE-654, UNKP-21-5-SZTE-579]; New National Excellence Program of the Ministry for Innovation and Technology - National Research, Development and Innovation Fund [UNKP-20-3 -SZTE-452]; Doctoral Student Scholarship Program of the Co-Operative Doctoral Program of the Ministry of Innovation and Technology - National Research, Development and Innovation Fund [KDP-17-4/ PALY-2021, C992025]; European Union's Horizon 2020 research and innovation programme under Marie Sklodowska-Curie grant [754432]; Polish Ministry of Science and Higher Education; National Academy of Scientist Education Program of the National Biomedical Foundation under Hungarian Ministry of Culture and Innovation; National Laboratory for Health Security [RRF-2.3.1-212022-00006, GINOP-2.3.2-15-2016-00014, GINOP-2.3.2-15-2016-00020, GINOP-2.3.2-15-2016-00035]; Janos Bolyai Research Fellowship from the Hungarian Academy of Sciences [BO/352/20, BO/00303/19/8]; [GINOP-2.3.4-15-2020-00010]; [GINOP-2.3.1-20-2020-00001]; [BECOMING-2019-1-HU01-KA203-061251] Funding text: We thank D. Verma from the Department of Microbiology and B. Bhimrao of Ambedkar University, Lucknow, India for help with soil sample collection and NBA approval. This work was supported by National Laboratory of Biotechnology Grants NKFIH-871-3/2020 and 2022-2.1.1-NL-2022-00008 (B.K. and C.P.); the European Union's Horizon 2020 research and innovation programme under grant agreement no. 739593 (B.P. and B.K.); the European Research Council H2020-ERC-2014-CoG 648364-Resistance Evolution (C.P.) and H2020-ERC-2019-PoC 862077-Aware (C.P.); National Research, Development and Innovation Office grant FK-135245 (B.K.) and FK-124254 (O.M.); the National Research, Development and Innovation Office and the Ministry for Innovation and Technology under the `Frontline' Programme KKP 129814 and 126506 (B.P. and C.P.); the National Laboratory for Health Security RRF-2.3.1-212022-00006 (B.P.), GINOP-2.3.2-15-2016-00014 (EVOMER, C.P. and B.P.), GINOP-2.3.2-15-2016-00020 (MolMedEx TUMORDNS, C.P.), GINOP-2.3.2-15-2016-00035 (N.Z.); a Janos Bolyai Research Fellowship from the Hungarian Academy of Sciences (BO/352/20 (B.K.), BO/00303/19/8 (O.M)); New National Excellence Program of the Ministry of Human Capacities (UNKP-20-5-SZTE-654 and UNKP-215-SZTE-579, B.K.); New National Excellence Program of the Ministry for Innovation and Technology funded by the National Research, Development and Innovation Fund (UNKP-20-3 -SZTE-452, G.A.); the Doctoral Student Scholarship Program of the Co-Operative Doctoral Program of the Ministry of Innovation and Technology financed by the National Research, Development and Innovation Fund (KDP-17-4/ PALY-2021, C992025, M.S.). R.H., B.G., P.U. and A.G. were supported by GINOP-2.3.4-15-2020-00010, GINOP-2.3.1-20-2020-00001, BECOMING-2019-1-HU01-KA203-061251, the European Union's Horizon 2020 research and innovation programme under Marie Sklodowska-Curie grant agreement no. 754432 and the Polish Ministry of Science and Higher Education, from the financial resources for science in 2018-2023. This research work was conducted with the support of the National Academy of Scientist Education Program of the National Biomedical Foundation under the sponsorship of the Hungarian Ministry of Culture and Innovation (D.K.).
Subjects: Q Science / természettudomány > QH Natural history / természetrajz > QH301 Biology / biológia > QH3011 Biochemistry / biokémia
Q Science / természettudomány > QH Natural history / természetrajz > QH301 Biology / biológia > QH3015 Molecular biology / molekuláris biológia
Q Science / természettudomány > QR Microbiology / mikrobiológia
SWORD Depositor: MTMT SWORD
Depositing User: MTMT SWORD
Date Deposited: 25 Sep 2023 09:00
Last Modified: 25 Sep 2023 09:00
URI: http://real.mtak.hu/id/eprint/174706

Actions (login required)

Edit Item Edit Item