Antimicrobial Peptides Can Generate Tolerance by Lag and Interfere with Antimicrobial Therapy
Antimicrobial peptides (AMPs) are widely distributed molecules secreted mostly by cells of the innate immune system to prevent bacterial proliferation at the site of infection. As with classic antibiotics, continued treatment with AMPs can create resistance in bacteria. However, whether AMPs can gen...
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| Format: | Article |
| Language: | English |
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MDPI AG
2022-10-01
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| Series: | Pharmaceutics |
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| Online Access: | https://www.mdpi.com/1999-4923/14/10/2169 |
| _version_ | 1797470309654200320 |
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| author | Daniel Sandín Javier Valle Jordi Morata David Andreu Marc Torrent |
| author_facet | Daniel Sandín Javier Valle Jordi Morata David Andreu Marc Torrent |
| author_sort | Daniel Sandín |
| collection | DOAJ |
| description | Antimicrobial peptides (AMPs) are widely distributed molecules secreted mostly by cells of the innate immune system to prevent bacterial proliferation at the site of infection. As with classic antibiotics, continued treatment with AMPs can create resistance in bacteria. However, whether AMPs can generate tolerance as an intermediate stage towards resistance is not known. Here, we show that the treatment of <i>Escherichia coli</i> with different AMPs induces tolerance by lag, particularly for those peptides that have internal targets. This tolerance can be detected as different morphological and physiological changes, which depend on the type of peptide molecule the bacterium has been exposed to. In addition, we show that AMP tolerance can also affect antibiotic treatment. The genomic sequencing of AMP-tolerant strains shows that different mutations alter membrane composition, DNA replication, and translation. Some of these mutations have also been observed in antibiotic-resistant strains, suggesting that AMP tolerance could be a relevant step in the development of antibiotic resistance. Monitoring AMP tolerance is relevant <i>vis-á-vis</i> the eventual therapeutic use of AMPs and because cross-tolerance might favor the emergence of resistance against conventional antibiotic treatments. |
| first_indexed | 2024-03-09T19:34:47Z |
| format | Article |
| id | doaj.art-8ad93177274f40ec9e5acf6a70c60d41 |
| institution | Directory Open Access Journal |
| issn | 1999-4923 |
| language | English |
| last_indexed | 2024-03-09T19:34:47Z |
| publishDate | 2022-10-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Pharmaceutics |
| spelling | doaj.art-8ad93177274f40ec9e5acf6a70c60d412023-11-24T01:57:27ZengMDPI AGPharmaceutics1999-49232022-10-011410216910.3390/pharmaceutics14102169Antimicrobial Peptides Can Generate Tolerance by Lag and Interfere with Antimicrobial TherapyDaniel Sandín0Javier Valle1Jordi Morata2David Andreu3Marc Torrent4Systems Biology of Infection Lab, Department of Biochemistry and Molecular Biology, Universitat Autònoma de Barcelona, Cerdanyola del Vallés 08193, SpainDepartment of Medicine and Life Sciences, Universitat Pompeu Fabra, Barcelona Biomedical Research Park, Barcelona 08003, SpainCNAG-CRG, Centre for Genomic Regulation (CRG), The Barcelona Institute of Science and Technology, Baldiri Reixac 4, Barcelona 08028, SpainDepartment of Medicine and Life Sciences, Universitat Pompeu Fabra, Barcelona Biomedical Research Park, Barcelona 08003, SpainSystems Biology of Infection Lab, Department of Biochemistry and Molecular Biology, Universitat Autònoma de Barcelona, Cerdanyola del Vallés 08193, SpainAntimicrobial peptides (AMPs) are widely distributed molecules secreted mostly by cells of the innate immune system to prevent bacterial proliferation at the site of infection. As with classic antibiotics, continued treatment with AMPs can create resistance in bacteria. However, whether AMPs can generate tolerance as an intermediate stage towards resistance is not known. Here, we show that the treatment of <i>Escherichia coli</i> with different AMPs induces tolerance by lag, particularly for those peptides that have internal targets. This tolerance can be detected as different morphological and physiological changes, which depend on the type of peptide molecule the bacterium has been exposed to. In addition, we show that AMP tolerance can also affect antibiotic treatment. The genomic sequencing of AMP-tolerant strains shows that different mutations alter membrane composition, DNA replication, and translation. Some of these mutations have also been observed in antibiotic-resistant strains, suggesting that AMP tolerance could be a relevant step in the development of antibiotic resistance. Monitoring AMP tolerance is relevant <i>vis-á-vis</i> the eventual therapeutic use of AMPs and because cross-tolerance might favor the emergence of resistance against conventional antibiotic treatments.https://www.mdpi.com/1999-4923/14/10/2169toleranceantimicrobial peptidesantimicrobial peptide LL-37pleurocidinpolymyxin Bdermaseptin |
| spellingShingle | Daniel Sandín Javier Valle Jordi Morata David Andreu Marc Torrent Antimicrobial Peptides Can Generate Tolerance by Lag and Interfere with Antimicrobial Therapy Pharmaceutics tolerance antimicrobial peptides antimicrobial peptide LL-37 pleurocidin polymyxin B dermaseptin |
| title | Antimicrobial Peptides Can Generate Tolerance by Lag and Interfere with Antimicrobial Therapy |
| title_full | Antimicrobial Peptides Can Generate Tolerance by Lag and Interfere with Antimicrobial Therapy |
| title_fullStr | Antimicrobial Peptides Can Generate Tolerance by Lag and Interfere with Antimicrobial Therapy |
| title_full_unstemmed | Antimicrobial Peptides Can Generate Tolerance by Lag and Interfere with Antimicrobial Therapy |
| title_short | Antimicrobial Peptides Can Generate Tolerance by Lag and Interfere with Antimicrobial Therapy |
| title_sort | antimicrobial peptides can generate tolerance by lag and interfere with antimicrobial therapy |
| topic | tolerance antimicrobial peptides antimicrobial peptide LL-37 pleurocidin polymyxin B dermaseptin |
| url | https://www.mdpi.com/1999-4923/14/10/2169 |
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