Jangir Pramod Kumar
Chemical-genetic profiling to investigate cross-resistance and collateral sensitivity between antimicrobial peptides.
[Thesis]
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Abstract in foreign language
Antimicrobial peptides (AMPs) are crucial components of the host immune system and have been proposed as promising novel anti-infectives. However, there is a serious concern that therapeutic application of AMPs would drive bacterial cross-resistance to our own immunity peptides. Our knowledge of cross-resistance between AMPs remains extremely limited. To address this gap, we used chemical-genetic approaches to uncover the resistance determinants of E. coli against 15 different AMPs. This comprehensive compendium revealed multiple and functionally diverse genes that modulate bacterial susceptibility to different AMPs. Interestingly, AMPs differ considerably in their resistance determinants, and resistance-enhancing genes overlap only to a limited extent between AMPs. As a consequence, collateral sensitivity effects were common: numerous genes decreased susceptibility to one AMP while simultaneously sensitized to others. Finally, by integrating laboratory evolution approach, we showed that our chemical-genetic map informed on the cross-resistance interactions between AMPs. In the future, the chemical-genetic map could inform efforts to avoid cross-resistance between therapeutic and human host AMPs.
Item Type: | Thesis (Doctoral thesis (PhD)) |
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Creators: | Jangir Pramod Kumar |
Supervisor(s): | Supervisor Position, academic title, institution MTMT author ID Pál Csaba Biokémiai Intézet MTA SZBK, Lendület Szintetikus és Rendszerbiológiai Kutatócsoport MTA SZBK / BKI 10027825 Kintses Bálint Biokémiai Intézet MTA SZBK 10045675 |
Subjects: | 01. Natural sciences > 01.06. Biological sciences |
Divisions: | Doctoral School of Biology |
Discipline: | Natural Sciences > Biology |
Language: | English |
Date: | 2020. February 25. |
Item ID: | 10231 |
MTMT identifier of the thesis: | 31390855 |
doi: | https://doi.org/10.14232/phd.10231 |
Date Deposited: | 2019. Aug. 26. 08:36 |
Last Modified: | 2020. Jul. 29. 10:40 |
Depository no.: | B 6588 |
URI: | https://doktori.bibl.u-szeged.hu/id/eprint/10231 |
Defence/Citable status: | Defended. |
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