Thesis supervisor: László Kredics
co-supervisor: Tamás Marik
Location of studies (in Hungarian): Department of Microbiology, Faculty of Science and Informatics, University of Szeged Abbreviation of location of studies: SZTE
Description of the research topic:
Many bioactive peptides have been reported to be a potential avenue in the treatment of various diseases, and peptaibols are one such group of bioactive peptides. Unveiling of their molecular mechanism of action requires elaborate and carefully designed experimentation. We aim to combine the molecular level experiments of computational simulation techniques with the accuracy and real-world implications of experimental techniques to elucidate the activity of novel fungal peptaibols against common agents causing bacteraemia and their multi-resistant variants. The other part of this research involves finding out whether peptaibols can have a long term effect on plants by inducing systemic resistance and find application as agents of biological control. The results of this study may direct us towards a new class of antimicrobial peptides with better understanding of their interaction with various cell-membranes and whether they can be effectively used as therapeutic or biocontrol agents.
Our main objective is to ascertain whether peptaibols have the ability to evolve as the next line of therapeutics against multi-resistant human bacterial pathogens, especially, those responsible for causing bacteraemia. The detailed analysis of their mode of action will be studied by molecular-level modelling against bacterial membrane-mimics so that future directions of antimicrobial peptide therapeutics can be elucidated. On the other hand, ISR of tomato plants will be investigated, whether peptaibols can have a long term effect on plants as novel biocontrol agents.
In case of their role against resistant S. aureus, it has been shown that peptides are highly effective against these bacteria. Daptomycin is an active peptide compound used to treat infections caused by drug resistant MRSA strains, but unfortunately, cases of daptomycin resistance have also been reported all over the world. The mechanism of resistance towards daptomycin lies in the modification of the cell membrane by modulation of phosphatidylglycerol (PG) lipids to lysyl-PG lipids (thereby making it less electronegative) presumably to prevent the positively charged daptomycin insertion due to electrostatic repulsion. Because peptaibols do not carry charge in their overall structure, they may prove to be effective against such a change in the host membranes.
Members of clade Longibrachiatum of Trichoderma can be opportunistic human pathogens. Because of their thermotolerant nature, they are used as biocontrol agents in tropical agricultural fields. If peptaibols are proven to induce long term ISR in cultivated plants, the risk of using opportunistic human pathogens could be avoided.
Required language skills: English Number of students who can be accepted: 1
Deadline for application: 2022-09-01
2024. IV. 17. ODT ülés Az ODT következő ülésére 2024. június 14-én, pénteken 10.00 órakor kerül sor a Semmelweis Egyetem Szenátusi termében (Bp. Üllői út 26. I. emelet).
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