Chemical-genetic profiling reveals cross-resistance and collateral sensitivity between antimicrobial peptides
Chemical-genetic profiling reveals cross-resistance and collateral sensitivity between antimicrobial peptides
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, with a chemical-genetic approach, we systematically assessed the resistance determinants of Escherichia coli against 15 different AMPs. Although generalizations about AMP resistance are common in the literature, we found that AMPs with different physicochemical properties and cellular targets vary considerably in their resistance determinants. As a consequence, collateral sensitivity effects were common: numerous genes decreased susceptibility to one AMP while simultaneously sensitized to others. Finally, the chemical-genetic map predicted the cross-resistance spectrum of laboratory-evolved human-B-defensin-3 resistant lineages. Our work substantially broadens the scope of known resistance-modulating genes and explores the pleiotropic effects of AMP resistance. In the future, the chemicalgenetic map could inform efforts to minimize cross-resistance between therapeutic and human host AMPs.
M¨|hi Orsolya、Spohn R¨|ka、Martins Ana、Hosseinnia Ali、Gy?rkei ¨￠d¨￠m、Ari Eszter、L¨￠z¨￠r Vikt¨?ria、Bodai L¨￠szl¨?、Fekete Gergely、P¨￠l Csaba、Nagy Istv¨￠n、Kintses B¨￠lint、Jangir Pramod K.、Sz¨￠mel M¨?nika、Cs?rg? B¨￠lint、Farag¨? Anik¨?、Daruka Lejla、Papp Bal¨￠zs、Kim Sunyoung、Babu Mohan、Phanse Sadhna、Gagarinova Alla
Synthetic and Systems Biology Unit, Institute of Biochemistry, Biological Research Centre of the Hungarian Academy of SciencesSynthetic and Systems Biology Unit, Institute of Biochemistry, Biological Research Centre of the Hungarian Academy of SciencesSynthetic and Systems Biology Unit, Institute of Biochemistry, Biological Research Centre of the Hungarian Academy of SciencesDepartment of Biochemistry, University of ReginaSynthetic and Systems Biology Unit, Institute of Biochemistry, Biological Research Centre of the Hungarian Academy of SciencesSynthetic and Systems Biology Unit, Institute of Biochemistry, Biological Research Centre of the Hungarian Academy of Sciences||Department of Genetics, E?tv?s Lor¨￠nd UniversitySynthetic and Systems Biology Unit, Institute of Biochemistry, Biological Research Centre of the Hungarian Academy of Sciences||Present address: Faculty of Biology, Technion ¨C Israel Institute of TechnologyDepartment of Biochemistry and Molecular Biology, University of SzegedSynthetic and Systems Biology Unit, Institute of Biochemistry, Biological Research Centre of the Hungarian Academy of SciencesSynthetic and Systems Biology Unit, Institute of Biochemistry, Biological Research Centre of the Hungarian Academy of SciencesSequencing Platform, Institute of Biochemistry, Biological Research Centre of the Hungarian Academy of SciencesSynthetic and Systems Biology Unit, Institute of Biochemistry, Biological Research Centre of the Hungarian Academy of Sciences||Department of Biochemistry and Molecular Biology, University of SzegedSynthetic and Systems Biology Unit, Institute of Biochemistry, Biological Research Centre of the Hungarian Academy of Sciences||Doctoral School in Biology, Faculty of Science and Informatics, University of SzegedSynthetic and Systems Biology Unit, Institute of Biochemistry, Biological Research Centre of the Hungarian Academy of Sciences||Doctoral School in Biology, Faculty of Science and Informatics, University of SzegedSynthetic and Systems Biology Unit, Institute of Biochemistry, Biological Research Centre of the Hungarian Academy of Sciences||Present address: Department of Microbiology and Immunology, University of CaliforniaDepartment of Biochemistry and Molecular Biology, University of SzegedSynthetic and Systems Biology Unit, Institute of Biochemistry, Biological Research Centre of the Hungarian Academy of SciencesSynthetic and Systems Biology Unit, Institute of Biochemistry, Biological Research Centre of the Hungarian Academy of SciencesDepartment of Biochemistry, University of ReginaDepartment of Biochemistry, University of ReginaDepartment of Biochemistry, University of ReginaDepartment of Biochemistry, University of Saskatchewan
生物科学研究方法、生物科学研究技术微生物学分子生物学
M¨|hi Orsolya,Spohn R¨|ka,Martins Ana,Hosseinnia Ali,Gy?rkei ¨￠d¨￠m,Ari Eszter,L¨￠z¨￠r Vikt¨?ria,Bodai L¨￠szl¨?,Fekete Gergely,P¨￠l Csaba,Nagy Istv¨￠n,Kintses B¨￠lint,Jangir Pramod K.,Sz¨￠mel M¨?nika,Cs?rg? B¨￠lint,Farag¨? Anik¨?,Daruka Lejla,Papp Bal¨￠zs,Kim Sunyoung,Babu Mohan,Phanse Sadhna,Gagarinova Alla.Chemical-genetic profiling reveals cross-resistance and collateral sensitivity between antimicrobial peptides[EB/OL].(2025-03-28)[2025-06-27].https://www.biorxiv.org/content/10.1101/542548.点此复制
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