Abstract

Antimicrobial peptides (AMPs) are promising antimicrobials, however, the potential of bacterial resistance is a major concern. Here we systematically study the evolution of resistance to 14 chemically diverse AMPs and 12 antibiotics in Escherichia coli. Our work indicates that evolution of resistance against certain AMPs, such as tachyplesin II and cecropin P1, is limited. Resistance level provided by point mutations and gene amplification is very low and antibiotic-resistant bacteria display no cross-resistance to these AMPs. Moreover, genomic fragments derived from a wide range of soil bacteria confer no detectable resistance against these AMPs when introduced into native host bacteria on plasmids. We have found that simple physicochemical features dictate bacterial propensity to evolve resistance against AMPs. Our work could serve as a promising source for the development of new AMP-based therapeutics less prone to resistance, a feature necessary to avoid any possible interference with our innate immune system.

Details

Title
Integrated evolutionary analysis reveals antimicrobial peptides with limited resistance
Author
Spohn, Réka 1 ; Daruka, Lejla 2 ; Lázár, Viktória 3 ; Martins, Ana 1 ; Fanni Vidovics 1 ; Grézal, Gábor 4   VIAFID ORCID Logo  ; Méhi, Orsolya 1 ; Kintses, Bálint 5 ; Számel, Mónika 2 ; Jangir, Pramod K 2 ; Csörgő, Bálint 6 ; Györkei, Ádám 4 ; Bódi, Zoltán 1 ; Faragó, Anikó 7 ; Bodai, László 8   VIAFID ORCID Logo  ; Földesi, Imre 9 ; Kata, Diána 9 ; Maróti, Gergely 10 ; Pap, Bernadett 10 ; Wirth, Roland 11 ; Papp, Balázs 4 ; Pál, Csaba 1   VIAFID ORCID Logo 

1  Synthetic and Systems Biology Unit, Institute of Biochemistry, Biological Research Centre, Szeged, Hungary 
2  Synthetic and Systems Biology Unit, Institute of Biochemistry, Biological Research Centre, Szeged, Hungary; Doctoral School of Biology, Faculty of Science and Informatics, University of Szeged, Szeged, Hungary 
3  Synthetic and Systems Biology Unit, Institute of Biochemistry, Biological Research Centre, Szeged, Hungary; Faculty of Biology, Technion - Israel Institute of Technology, Haifa, Israel 
4  Synthetic and Systems Biology Unit, Institute of Biochemistry, Biological Research Centre, Szeged, Hungary; HCEMM-BRC Metabolic Systems Biology Lab, Szeged, Hungary 
5  Synthetic and Systems Biology Unit, Institute of Biochemistry, Biological Research Centre, Szeged, Hungary; Department of Biochemistry and Molecular Biology, University of Szeged, Szeged, Hungary 
6  Synthetic and Systems Biology Unit, Institute of Biochemistry, Biological Research Centre, Szeged, Hungary; University of California, San Francisco, Department of Microbiology and Immunology, San Francisco, CA, USA 
7  Doctoral School of Biology, Faculty of Science and Informatics, University of Szeged, Szeged, Hungary; Department of Biochemistry and Molecular Biology, University of Szeged, Szeged, Hungary 
8  Department of Biochemistry and Molecular Biology, University of Szeged, Szeged, Hungary 
9  Department of Laboratory Medicine, University of Szeged, Szeged, Hungary 
10  Institute of Plant Biology, Biological Research Centre, Hungarian Academy of Sciences, Szeged, Hungary 
11  Department of Biotechnology, University of Szeged, Szeged, Hungary 
Pages
1-13
Publication year
2019
Publication date
Oct 2019
Publisher
Nature Publishing Group
e-ISSN
20411723
Source type
Scholarly Journal
Language of publication
English
DOI
https://doi.org/10.1038/s41467-019-12364-6
ProQuest document ID
2300955357
Copyright
© 2019. This work is published under http://creativecommons.org/licenses/by/4.0/ (the “License”). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.