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resistance evolution SIGNED

Bacterial evolution of hypersensitivity and resistance against antimicrobial peptides

Total Cost €

EC-Contrib. €

Partnership

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Outcomes and
results

resistance evolution project word cloud

Explore the words cloud of the resistance evolution project. It provides you a very rough idea of what is the project "resistance evolution" about.

desirable computational driving collateral readily questions vulnerable phenotypic assays microbes roles predictable integrate protection occurring immune unclear single tools throughput alternatives sensitivities molecular genomics hypersensitive simultaneously offs fitness agents drug frequently amps compromise drive points resistance biology cross largely multiple evolutionary therapeutic induce naturally laboratory rigorously bacteria genetic last evolution pathogenic sensitivity relatively chemical peptides trade peptide decreases drugs immunity functional underlying certain antibiotics modulatory natural mechanisms explore central shortage limited properties systematic resistant bacterial guidelines pathogens amp antimicrobial

Project "resistance evolution" data sheet

The following table provides information about the project.

Coordinator	SZEGEDI BIOLOGIAI KUTATOKOZPONT Organization address address: TEMESVARI KORUT 62 city: SZEGED postcode: 6726 website: www1.szbk.u-szeged.hu contact info title: n.a. name: n.a. surname: n.a. function: n.a. email: n.a. telephone: n.a. fax: n.a.
Coordinator Country	Hungary [HU]
Project website	http://group.szbk.u-szeged.hu/sysbiol/pal-csaba-lab-index.html
Total cost	1˙846˙250 €
EC max contribution	1˙846˙250 € (100%)
Programme	1. H2020-EU.1.1. (EXCELLENT SCIENCE - European Research Council (ERC))
Code Call	ERC-2014-CoG
Funding Scheme	ERC-COG
Starting year	2015
Duration (year-month-day)	from 2015-10-01 to 2021-09-30

Partnership

Take a look of project's partnership.

#	participants	country	role	EC contrib. [€]
1	SZEGEDI BIOLOGIAI KUTATOKOZPONT SZEGEDI BIOLOGIAI KUTATOKOZPONT Organization address address: TEMESVARI KORUT 62 city: SZEGED postcode: 6726 website: www1.szbk.u-szeged.hu contact info title: n.a. name: n.a. surname: n.a. function: n.a. email: n.a. telephone: n.a. fax: n.a.	HU (SZEGED)	coordinator	1˙846˙250.00

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Project objective

Evolution of resistance towards a single drug simultaneously increases (cross-resistance) or decreases (collateral sensitivity) fitness to multiple other antimicrobial agents. The molecular mechanisms driving cross-resistance are relatively well described, but it remains largely unclear how frequently does genetic adaptation to a single drug increase the sensitivity to others and what the underlying molecular mechanisms of collateral sensitivity are. This proposal focuses on studying the bacterial evolution of resistance and collateral sensitivity against antimicrobial peptides (AMPs). Beyond their modulatory roles in the immune system, these naturally occurring peptides provide protection against pathogenic microbes, and are considered as promising novel alternatives to traditional antibiotics. However, there are concerns that evolution against therapeutic AMPs can readily develop and as a by-product this might compromise natural immunity. Our knowledge of these issues is limited due to the shortage of systematic evolutionary studies. Therefore, the three central questions we address are: Do bacteria resistant to multiple antibiotics become hypersensitive to certain antimicrobial peptides? What are the evolutionary mechanisms leading to AMP resistance and to what extent does this process induce cross-resistance/collateral sensitivity against other drugs? Last, are these evolutionary trade-offs predictable based on chemical and functional peptide properties? To investigate these issues rigorously, we integrate tools of laboratory evolution, high-throughput phenotypic assays, functional genomics, and computational systems biology. Our project will provide an insight into the evolutionary mechanisms that drive cross-resistance and collateral sensitivities with the aim to explore the vulnerable points of resistant bacteria. Another goal is to provide guidelines for the future design of antimicrobial peptides with desirable properties against bacterial pathogens.

Publications

List of publications.
year	authors and title	journal	last update
2016	IldikÃ³ Karcagi, GÃ¡bor Draskovits, Kinga Umenhoffer, Gergely Fekete, KÃ¡roly KovÃ¡cs, Orsolya MÃ©hi, Gabriella BalikÃ³, BalÃ¡zs Szappanos, Zsuzsanna GyÃ¶rfy, TamÃ¡s FehÃ©r, BalÃ¡zs Bogos, Frederick R. Blattner, Csaba PÃ¡l, GyÃ¶rgy PÃ³sfai, BalÃ¡zs Papp Indispensability of Horizontally Transferred Genes and Its Impact on Bacterial Genome Streamlining published pages: 1257-1269, ISSN: 0737-4038, DOI: 10.1093/molbev/msw009	Molecular Biology and Evolution 33/5	2019-10-15
2017	ZoltÃ¡n BÃ³di, ZoltÃ¡n Farkas, Dmitry Nevozhay, Dorottya Kalapis, ViktÃ³ria LÃ¡zÃ¡r, BÃ¡lint CsÃ¶rgÅ‘, Ãkos Nyerges, BÃ©la Szamecz, Gergely Fekete, BalÃ¡zs Papp, Hugo AraÃºjo, JosÃ© L. Oliveira, Gabriela Moura, Manuel A. S. Santos, TamÃ¡s SzÃ©kely Jr, GÃ¡bor BalÃ¡zsi, Csaba PÃ¡l Phenotypic heterogeneity promotes adaptive evolution published pages: e2000644, ISSN: 1545-7885, DOI: 10.1371/journal.pbio.2000644	PLOS Biology 15/5	2019-10-15
2016	Junchen Diao, Daniel A. Charlebois, Dmitry Nevozhay, ZoltÃ¡n BÃ³di, Csaba PÃ¡l, GÃ¡bor BalÃ¡zsi Efflux Pump Control Alters Synthetic Gene Circuit Function published pages: 619-631, ISSN: 2161-5063, DOI: 10.1021/acssynbio.5b00154	ACS Synthetic Biology 5/7	2019-10-15
2017	Csaba PÃ¡l, BalÃ¡zs Papp Evolution of complex adaptations in molecular systems published pages: 1084-1092, ISSN: 2397-334X, DOI: 10.1038/s41559-017-0228-1	Nature Ecology & Evolution 1/8	2019-10-15
2015	Csaba PÃ¡l, BalÃ¡zs Papp, ViktÃ³ria LÃ¡zÃ¡r Collateral sensitivity of antibiotic-resistant microbes published pages: 401-407, ISSN: 0966-842X, DOI: 10.1016/j.tim.2015.02.009	Trends in Microbiology 23/7	2019-10-15
2016	BalÃ¡zs Szappanos, Jonathan Fritzemeier, BÃ¡lint CsÃ¶rgÅ‘, ViktÃ³ria LÃ¡zÃ¡r, Xiaowen Lu, Gergely Fekete, BalÃ¡zs BÃ¡lint, RÃ³bert Herczeg, IstvÃ¡n Nagy, Richard A. Notebaart, Martin J. Lercher, Csaba PÃ¡l, BalÃ¡zs Papp Adaptive evolution of complex innovations through stepwise metabolic niche expansion published pages: 11607, ISSN: 2041-1723, DOI: 10.1038/ncomms11607	Nature Communications 7	2019-10-15
2016	Ãkos Nyerges, BÃ¡lint CsÃ¶rgÅ‘, IstvÃ¡n Nagy, BalÃ¡zs BÃ¡lint, PÃ©ter Bihari, ViktÃ³ria LÃ¡zÃ¡r, GÃ¡bor Apjok, Kinga Umenhoffer, BalÃ¡zs Bogos, GyÃ¶rgy PÃ³sfai, Csaba PÃ¡l A highly precise and portable genome engineering method allows comparison of mutational effects across bacterial species published pages: 2502-2507, ISSN: 0027-8424, DOI: 10.1073/pnas.1520040113	Proceedings of the National Academy of Sciences 113/9	2019-10-15
2015	Dorottya Kalapis, Ana R. Bezerra, ZoltÃ¡n Farkas, Peter Horvath, ZoltÃ¡n BÃ³di, Andreea Daraba, BÃ©la Szamecz, Ivo Gut, MÃ³nica Bayes, Manuel A. S. Santos, Csaba PÃ¡l Evolution of Robustness to Protein Mistranslation by Accelerated Protein Turnover published pages: e1002291, ISSN: 1545-7885, DOI: 10.1371/journal.pbio.1002291	PLOS Biology 13/11	2019-10-15
2018	ViktÃ³ria LÃ¡zÃ¡r, Ana Martins, RÃ©ka Spohn, Lejla Daruka, GÃ¡bor GrÃ©zal, Gergely Fekete, MÃ³nika SzÃ¡mel, Pramod K Jangir, BÃ¡lint Kintses, BÃ¡lint CsÃ¶rgÅ‘, Ãkos Nyerges, ÃdÃ¡m GyÃ¶rkei, AndrÃ¡s Kincses, AndrÃ¡s DÃ©r, Fruzsina R Walter, MÃ¡ria A Deli, Edit UrbÃ¡n, ZsÃ³fia HegedÅ±s, GÃ¡bor Olajos, Orsolya MÃ©hi, BalÃ¡zs BÃ¡lint, IstvÃ¡n Nagy, TamÃ¡s A Martinek, BalÃ¡zs Papp, Csaba PÃ¡l Antibiotic-resistant bacteria show widespread collateral sensitivity to antimicrobial peptides published pages: 718-731, ISSN: 2058-5276, DOI: 10.1038/s41564-018-0164-0	Nature Microbiology 3/6	2019-10-15

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