Chemical-genetic profiling reveals limited cross-resistance between antimicrobial peptides with different modes of action

Bálint Kintses (), Pramod K. Jangir, Gergely Fekete, Mónika Számel, Orsolya Méhi, Réka Spohn, Lejla Daruka, Ana Martins, Ali Hosseinnia, Alla Gagarinova, Sunyoung Kim, Sadhna Phanse, Bálint Csörgő, Ádám Györkei, Eszter Ari, Viktória Lázár, István Nagy, Mohan Babu, Csaba Pál () and Balázs Papp ()
Additional contact information
Bálint Kintses: Institute of Biochemistry, Biological Research Centre
Pramod K. Jangir: Institute of Biochemistry, Biological Research Centre
Gergely Fekete: Institute of Biochemistry, Biological Research Centre
Mónika Számel: Institute of Biochemistry, Biological Research Centre
Orsolya Méhi: Institute of Biochemistry, Biological Research Centre
Réka Spohn: Institute of Biochemistry, Biological Research Centre
Lejla Daruka: Institute of Biochemistry, Biological Research Centre
Ana Martins: Institute of Biochemistry, Biological Research Centre
Ali Hosseinnia: University of Regina
Alla Gagarinova: University of Saskatchewan
Sunyoung Kim: University of Regina
Sadhna Phanse: University of Regina
Bálint Csörgő: Institute of Biochemistry, Biological Research Centre
Ádám Györkei: Institute of Biochemistry, Biological Research Centre
Eszter Ari: Institute of Biochemistry, Biological Research Centre
Viktória Lázár: Institute of Biochemistry, Biological Research Centre
István Nagy: Institute of Biochemistry, Biological Research Centre
Mohan Babu: University of Regina
Csaba Pál: Institute of Biochemistry, Biological Research Centre
Balázs Papp: Institute of Biochemistry, Biological Research Centre

Nature Communications, 2019, vol. 10, issue 1, 1-13

Abstract: Abstract Antimicrobial peptides (AMPs) are key effectors of the innate immune system and promising therapeutic agents. Yet, knowledge on how to design AMPs with minimal cross-resistance to human host-defense peptides remains limited. Here, we systematically assess the resistance determinants of Escherichia coli against 15 different AMPs using chemical-genetics and compare to the cross-resistance spectra of laboratory-evolved AMP-resistant strains. Although generalizations about AMP resistance are common in the literature, we find that AMPs with different physicochemical properties and cellular targets vary considerably in their resistance determinants. As a consequence, cross-resistance is prevalent only between AMPs with similar modes of action. Finally, our screen reveals several genes that shape susceptibility to membrane- and intracellular-targeting AMPs in an antagonistic manner. We anticipate that chemical-genetic approaches could inform future efforts to minimize cross-resistance between therapeutic and human host AMPs.

Date: 2019
References: Add references at CitEc
Citations:

Downloads: (external link)
https://www.nature.com/articles/s41467-019-13618-z Abstract (text/html)

Related works:
This item may be available elsewhere in EconPapers: Search for items with the same title.

Export reference: BibTeX RIS (EndNote, ProCite, RefMan) HTML/Text

Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:10:y:2019:i:1:d:10.1038_s41467-019-13618-z

Ordering information: This journal article can be ordered from
https://www.nature.com/ncomms/

DOI: 10.1038/s41467-019-13618-z

Access Statistics for this article

Nature Communications is currently edited by Nathalie Le Bot, Enda Bergin and Fiona Gillespie

More articles in Nature Communications from Nature
Bibliographic data for series maintained by Sonal Shukla () and Springer Nature Abstracting and Indexing ().