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resistance evolution SIGNED

Bacterial evolution of hypersensitivity and resistance against antimicrobial peptides

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EC-Contrib. €

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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 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

year authors and title journal last update
List of publications.
2016 Ildikó Karcagi, Gábor Draskovits, Kinga Umenhoffer, Gergely Fekete, Károly Kovács, Orsolya Méhi, Gabriella Balikó, Balázs Szappanos, Zsuzsanna Györfy, Tamás Fehér, Balázs Bogos, Frederick R. Blattner, Csaba Pál, György Pósfai, Balázs 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 Zoltán Bódi, Zoltán Farkas, Dmitry Nevozhay, Dorottya Kalapis, Viktória Lázár, Bálint Csörgő, Ákos Nyerges, Béla Szamecz, Gergely Fekete, Balázs Papp, Hugo Araújo, José L. Oliveira, Gabriela Moura, Manuel A. S. Santos, Tamás Székely Jr, Gábor Balázsi, Csaba Pál
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, Zoltán Bódi, Csaba Pál, Gábor Balázsi
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 Pál, Balázs 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 Pál, Balázs Papp, Viktória Lázár
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 Balázs Szappanos, Jonathan Fritzemeier, Bálint Csörgő, Viktória Lázár, Xiaowen Lu, Gergely Fekete, Balázs Bálint, Róbert Herczeg, István Nagy, Richard A. Notebaart, Martin J. Lercher, Csaba Pál, Balázs 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 Ákos Nyerges, Bálint Csörgő, István Nagy, Balázs Bálint, Péter Bihari, Viktória Lázár, Gábor Apjok, Kinga Umenhoffer, Balázs Bogos, György Pósfai, Csaba Pál
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, Zoltán Farkas, Peter Horvath, Zoltán Bódi, Andreea Daraba, Béla Szamecz, Ivo Gut, Mónica Bayes, Manuel A. S. Santos, Csaba Pál
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 Viktória Lázár, Ana Martins, Réka Spohn, Lejla Daruka, Gábor Grézal, Gergely Fekete, Mónika Számel, Pramod K Jangir, Bálint Kintses, Bálint Csörgő, Ákos Nyerges, Ádám Györkei, András Kincses, András Dér, Fruzsina R Walter, Mária A Deli, Edit Urbán, Zsófia Hegedűs, Gábor Olajos, Orsolya Méhi, Balázs Bálint, István Nagy, Tamás A Martinek, Balázs Papp, Csaba Pál
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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