Tuneable poration: host defense peptides as sequence probes for antimicrobial mechanisms
Autor: | Jason Crain, Valeria Losasso, Martyn Winn, Hasan Alkassem, Peter J. Judge, Maxim G. Ryadnov, Nilofar Faruqui, Bart W. Hoogenboom, Marc-Philipp Pfeil, Anthony Watts, Katharine Hammond, Baptiste Lamarre, Glenn J. Martyna, Jascindra Ravi, Alice L. B. Pyne |
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Jazyk: | angličtina |
Rok vydání: | 2020 |
Předmět: |
0301 basic medicine
Multidisciplinary 030102 biochemistry & molecular biology Drug discovery Chemistry lcsh:R Cecropin B lcsh:Medicine Sequence (biology) Computational biology Drug resistance Antimicrobial Article 03 medical and health sciences 030104 developmental biology lcsh:Q lcsh:Science Peptide sequence |
Zdroj: | Scientific Reports, Vol 8, Iss 1, Pp 1-15 (2018) Scientific Reports |
ISSN: | 2045-2322 |
Popis: | The spread of antimicrobial resistance stimulates discovery strategies that place emphasis on mechanisms circumventing the drawbacks of traditional antibiotics and on agents that hit multiple targets. Host defense peptides (HDPs) are promising candidates in this regard. Here we demonstrate that a given HDP sequence intrinsically encodes for tuneable mechanisms of membrane disruption. Using an archetypal HDP (cecropin B) we show that subtle structural alterations convert antimicrobial mechanisms from native carpet-like scenarios to poration and non-porating membrane exfoliation. Such distinct mechanisms, studied using low- and high-resolution spectroscopy, nanoscale imaging and molecular dynamics simulations, all maintain strong antimicrobial effects, albeit with diminished activity against pathogens resistant to HDPs. The strategy offers an effective search paradigm for the sequence probing of discrete antimicrobial mechanisms within a single HDP. |
Databáze: | OpenAIRE |
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