Jangir, Pramod Kumar and Ogunlana, Lois and Szili, Petra and Czikkely, Márton Simon and Shaw, Liam P and Stevens, Emily J and Yu, Yang and Yang, Qiue and Wang, Yang and Pál, Csaba and Walsh, Timothy R and MacLean, Craig R (2023) The evolution of colistin resistance increases bacterial resistance to host antimicrobial peptides and virulence. ELIFE, 12. No-e84395. ISSN 2050-084X
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Abstract
Antimicrobial peptides (AMPs) offer a promising solution to the antibiotic resistance crisis. However, an unresolved serious concern is that the evolution of resistance to therapeutic AMPs may generate cross-resistance to host AMPs, compromising a cornerstone of the innate immune response. We systematically tested this hypothesis using globally disseminated mobile colistin resistance (MCR) that has been selected by the use of colistin in agriculture and medicine. Here, we show that MCR provides a selective advantage to Escherichia coli in the presence of key AMPs from humans and agricultural animals by increasing AMP resistance. Moreover, MCR promotes bacterial growth in human serum and increases virulence in a Galleria mellonella infection model. Our study shows how the anthropogenic use of AMPs can drive the accidental evolution of resistance to the innate immune system of humans and animals. These findings have major implications for the design and use of therapeutic AMPs and suggest that MCR may be difficult to eradicate, even if colistin use is withdrawn.
| Item Type: | Article |
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| Additional Information: | Funding Agency and Grant Number: Wellcome Trust [106918/Z/15Z]; Medical Research Council [MR/S013768/1]; National Natural Science Foundation of China [81861138051]; European Research Council [GINOP-2.3.2-15-2016-00014, GINOP-2.3.2-15-2016-00020]; Hungarian Academy of Sciences Momentum [BB/M011224/1]; National Research, Development and Innovation Office [UNKP-21-4-New]; National Laboratories Program, National Laboratory of Biotechnology Grant [H2020-ERC-2019-PoC 862077]; National Research, Development and Innovation Office, Hungary; Biotechnology and Biological Sciences Research Council [LP -2017-10/2017]; Gazdasagfejlesztesi es Innovacios Operativ Program; Biotechnology and Biological Sciences Research Council; Ministry for Innovation and Technology Funding text: Wellcome Trust 106918/Z/15Z Craig R MacLeanMedical Research Council MR/S013768/1 Craig R MacLean Timothy R WalshNational Natural Science Foundation of China 81861138051 Yang WangEuropean Research Council H2020-ERC-2014-CoG 648364 -Resistance Evolution Csaba PalEuropean Research Council H2020-ERC-2019-PoC 862077-Aware Csaba PalHungarian Academy of Sciences Momentum 'Celzott Lenduelet' Programme LP -2017-10/2017 Csaba Pal National Research, Development and Innovation Office Elvonal' Programme KKP 126506 Csaba PalNational Laboratories Program, National Laboratory of Biotechnology Grant NKFIH-871-3/2020 Csaba Pal Gazdasagfejlesztesi es Innovacios Operativ Program GINOP-2.3.2-15-2016-00014 Csaba PalGazdasagfejlesztesi es Innovacios Operativ Program GINOP-2.3.2-15-2016-00020 (MolMedEx TUMORDNS Csaba PalBiotechnology and Biological Sciences Research Council BB/M011224/1 Liam P ShawMinistry for Innovation and Technology UNKP-21-4-New Petra Szili Ministry for Innovation and Technology FEIF/433-4/2020-ITM_ SZERZ Marton CzikkelyThe funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication. For the purpose of Open Access, the authors have applied a CC BY public copyright license to any Author Accepted Manuscript version arising from this submission. |
| Subjects: | Q Science / természettudomány > QH Natural history / természetrajz > QH301 Biology / biológia > QH3011 Biochemistry / biokémia Q Science / természettudomány > QR Microbiology / mikrobiológia |
| SWORD Depositor: | MTMT SWORD |
| Depositing User: | MTMT SWORD |
| Date Deposited: | 26 Sep 2023 09:40 |
| Last Modified: | 26 Sep 2023 09:40 |
| URI: | http://real.mtak.hu/id/eprint/174964 |
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