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Genomics of experimental adaptation of Staphylococcus aureus to a natural combination of insect antimicrobial peptides
Antimicrobial peptides (AMP) are highly conserved immune effectors across the tree of life and are employed as combinations. In the beetle Tenebrio molitor, a defensin and a coleoptericin are highly expressed in vivo after inoculation with S. aureus. The defensin displays strong in vitro activity bu...
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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Nature Publishing Group UK
2018
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6193990/ https://www.ncbi.nlm.nih.gov/pubmed/30337550 http://dx.doi.org/10.1038/s41598-018-33593-7 |
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author | Makarova, Olga Johnston, Paul Rodriguez-Rojas, Alexandro El Shazely, Baydaa Morales, Javier Moreno Rolff, Jens |
author_facet | Makarova, Olga Johnston, Paul Rodriguez-Rojas, Alexandro El Shazely, Baydaa Morales, Javier Moreno Rolff, Jens |
author_sort | Makarova, Olga |
collection | PubMed |
description | Antimicrobial peptides (AMP) are highly conserved immune effectors across the tree of life and are employed as combinations. In the beetle Tenebrio molitor, a defensin and a coleoptericin are highly expressed in vivo after inoculation with S. aureus. The defensin displays strong in vitro activity but no survival benefit in vivo. The coleoptericin provides a survival benefit in vivo, but no activity in vitro. This suggests a potentiating effect in vivo, and here we wanted to investigate the effects of this combination on resistance evolution using a bottom-approach in vitro starting with a combination of two abundant AMPs only. We experimentally evolved S. aureus in the presence of the defensin and a combination of the defensin and coleoptericin. Genome re-sequencing showed that resistance was associated with mutations in either the pmt or nsa operons. Strains with these mutations show longer lag phases, slower Vmax, and nsa mutants reach lower final population sizes. Mutations in the rpo operon showed a further increase in the lag phase in nsa mutants but not in pmt mutants. In contrast, final MICs (minimum inhibitory concentrations) do not differ according to mutation. All resistant lines display AMP but not antibiotic cross-resistance. Costly resistance against AMPs readily evolves for an individual AMP as well as a naturally occurring combination in vitro and provides broad protection against AMPs. Such non-specific resistance could result in strong selection on host immune systems that rely on cocktails of AMPs. |
format | Online Article Text |
id | pubmed-6193990 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2018 |
publisher | Nature Publishing Group UK |
record_format | MEDLINE/PubMed |
spelling | pubmed-61939902018-10-24 Genomics of experimental adaptation of Staphylococcus aureus to a natural combination of insect antimicrobial peptides Makarova, Olga Johnston, Paul Rodriguez-Rojas, Alexandro El Shazely, Baydaa Morales, Javier Moreno Rolff, Jens Sci Rep Article Antimicrobial peptides (AMP) are highly conserved immune effectors across the tree of life and are employed as combinations. In the beetle Tenebrio molitor, a defensin and a coleoptericin are highly expressed in vivo after inoculation with S. aureus. The defensin displays strong in vitro activity but no survival benefit in vivo. The coleoptericin provides a survival benefit in vivo, but no activity in vitro. This suggests a potentiating effect in vivo, and here we wanted to investigate the effects of this combination on resistance evolution using a bottom-approach in vitro starting with a combination of two abundant AMPs only. We experimentally evolved S. aureus in the presence of the defensin and a combination of the defensin and coleoptericin. Genome re-sequencing showed that resistance was associated with mutations in either the pmt or nsa operons. Strains with these mutations show longer lag phases, slower Vmax, and nsa mutants reach lower final population sizes. Mutations in the rpo operon showed a further increase in the lag phase in nsa mutants but not in pmt mutants. In contrast, final MICs (minimum inhibitory concentrations) do not differ according to mutation. All resistant lines display AMP but not antibiotic cross-resistance. Costly resistance against AMPs readily evolves for an individual AMP as well as a naturally occurring combination in vitro and provides broad protection against AMPs. Such non-specific resistance could result in strong selection on host immune systems that rely on cocktails of AMPs. Nature Publishing Group UK 2018-10-18 /pmc/articles/PMC6193990/ /pubmed/30337550 http://dx.doi.org/10.1038/s41598-018-33593-7 Text en © The Author(s) 2018 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/. |
spellingShingle | Article Makarova, Olga Johnston, Paul Rodriguez-Rojas, Alexandro El Shazely, Baydaa Morales, Javier Moreno Rolff, Jens Genomics of experimental adaptation of Staphylococcus aureus to a natural combination of insect antimicrobial peptides |
title | Genomics of experimental adaptation of Staphylococcus aureus to a natural combination of insect antimicrobial peptides |
title_full | Genomics of experimental adaptation of Staphylococcus aureus to a natural combination of insect antimicrobial peptides |
title_fullStr | Genomics of experimental adaptation of Staphylococcus aureus to a natural combination of insect antimicrobial peptides |
title_full_unstemmed | Genomics of experimental adaptation of Staphylococcus aureus to a natural combination of insect antimicrobial peptides |
title_short | Genomics of experimental adaptation of Staphylococcus aureus to a natural combination of insect antimicrobial peptides |
title_sort | genomics of experimental adaptation of staphylococcus aureus to a natural combination of insect antimicrobial peptides |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6193990/ https://www.ncbi.nlm.nih.gov/pubmed/30337550 http://dx.doi.org/10.1038/s41598-018-33593-7 |
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