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Antimicrobial peptide induced-stress renders Staphylococcus aureus susceptible to toxic nucleoside analogues

View ORCID ProfileAlexandro Rodríguez-Rojas, Arpita Nath, Baydaa El Shazely, Greta Santi, Joshua Jay Kim, View ORCID ProfileChristoph Weise, View ORCID ProfileBenno Kuropka, View ORCID ProfileJens Rolff
doi: https://doi.org/10.1101/2020.03.30.015206
Alexandro Rodríguez-Rojas
1Freie Universität Berlin, Institut für Biologie, Evolutionary Biology, Königin-Luise-Strasse 1-3, 14195 Berlin, Germany
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  • ORCID record for Alexandro Rodríguez-Rojas
  • For correspondence: a.rojas@fu-berlin.de
Arpita Nath
1Freie Universität Berlin, Institut für Biologie, Evolutionary Biology, Königin-Luise-Strasse 1-3, 14195 Berlin, Germany
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Baydaa El Shazely
1Freie Universität Berlin, Institut für Biologie, Evolutionary Biology, Königin-Luise-Strasse 1-3, 14195 Berlin, Germany
2Zoology Department, Faculty of Science, Alexandria University, Alexandria, Egypt
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Greta Santi
1Freie Universität Berlin, Institut für Biologie, Evolutionary Biology, Königin-Luise-Strasse 1-3, 14195 Berlin, Germany
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Joshua Jay Kim
1Freie Universität Berlin, Institut für Biologie, Evolutionary Biology, Königin-Luise-Strasse 1-3, 14195 Berlin, Germany
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Christoph Weise
3Freie Universität Berlin, Institute of Chemistry and Biochemistry, für Chemie und Biochemie, Thielallee 63, 14195 Berlin, Germany
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Benno Kuropka
3Freie Universität Berlin, Institute of Chemistry and Biochemistry, für Chemie und Biochemie, Thielallee 63, 14195 Berlin, Germany
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Jens Rolff
1Freie Universität Berlin, Institut für Biologie, Evolutionary Biology, Königin-Luise-Strasse 1-3, 14195 Berlin, Germany
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Abstract

Cationic antimicrobial peptides (AMPs) are active immune effectors of multicellular organisms and also considered as new antimicrobial drug candidates. One of the problems encountered when developing AMPs as drugs is the difficulty to reach sufficient killing concentrations under physiological conditions. Here, using pexiganan, a cationic peptide derived from a host defence peptide of the African clawed frog and the first AMP developed into an antibacterial drug, we studied if sub-lethal effects of AMPs can be harnessed to devise treatment combinations. We studied the pexiganan stress response of Staphylococcus aureus at sub-lethal concentrations using quantitative proteomics. Several proteins involved in nucleotide metabolism were elevated, suggesting a metabolic demand. We then show that S. aureus is highly susceptible to antimetabolite nucleoside analogues when exposed to pexiganan, even at sub-inhibitory concentrations. These findings could be used to enhance pexiganan potency while decreasing the risk of resistance emergence, and our findings can likely be extended to other antimicrobial peptides.

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  • An improved version, some errors were fixed.

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Posted April 04, 2020.
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Antimicrobial peptide induced-stress renders Staphylococcus aureus susceptible to toxic nucleoside analogues
Alexandro Rodríguez-Rojas, Arpita Nath, Baydaa El Shazely, Greta Santi, Joshua Jay Kim, Christoph Weise, Benno Kuropka, Jens Rolff
bioRxiv 2020.03.30.015206; doi: https://doi.org/10.1101/2020.03.30.015206
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Antimicrobial peptide induced-stress renders Staphylococcus aureus susceptible to toxic nucleoside analogues
Alexandro Rodríguez-Rojas, Arpita Nath, Baydaa El Shazely, Greta Santi, Joshua Jay Kim, Christoph Weise, Benno Kuropka, Jens Rolff
bioRxiv 2020.03.30.015206; doi: https://doi.org/10.1101/2020.03.30.015206

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