Pyrenebutyrate Enhances the Antibacterial Effect of Peptide-Coupled Antisense Peptide Nucleic Acids in <i>Streptococcus pyogenes</i>
Antisense peptide nucleic acids (PNAs) inhibit bacterial growth in several infection models. Since PNAs are not spontaneously taken up by bacteria, they are often conjugated to carriers such as cell-penetrating peptides (CPPs) in order to improve translocation. Hydrophobic counterions such as pyrene...
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| Format: | Article |
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MDPI AG
2023-08-01
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| Series: | Microorganisms |
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| Online Access: | https://www.mdpi.com/2076-2607/11/9/2131 |
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| author | Corina Abt Lisa Marie Gerlach Jana Bull Anette Jacob Bernd Kreikemeyer Nadja Patenge |
| author_facet | Corina Abt Lisa Marie Gerlach Jana Bull Anette Jacob Bernd Kreikemeyer Nadja Patenge |
| author_sort | Corina Abt |
| collection | DOAJ |
| description | Antisense peptide nucleic acids (PNAs) inhibit bacterial growth in several infection models. Since PNAs are not spontaneously taken up by bacteria, they are often conjugated to carriers such as cell-penetrating peptides (CPPs) in order to improve translocation. Hydrophobic counterions such as pyrenebutyrate (PyB) have been shown to facilitate translocation of peptides over natural and artificial membranes. In this study, the capability of PyB to support translocation of CPP-coupled antisense PNAs into bacteria was investigated in <i>Streptococcus pyogenes</i> and <i>Streptococcus pneumoniae</i>. PyB enhanced the antimicrobial activity of CPP-conjugated antisense PNAs in <i>S. pyogenes</i>. The most significant effect of PyB was observed in combination with K8-conjugated anti-<i>gyrA</i> PNAs. In contrast, no significant effect of PyB on the antimicrobial activity of CPP-conjugated PNAs in <i>S. pneumoniae</i> was detected. Uptake of K8-FITC into <i>S. pyogenes</i>, <i>Escherichia coli</i>, and <i>Klebsiella pneumoniae</i> could be improved by pre-incubation with PyB, indicating that PyB supports the antimicrobial effect of CPP-antisense PNAs in <i>S. pyogenes</i> by facilitating the translocation of peptides across the bacterial membrane. |
| first_indexed | 2024-03-10T22:27:30Z |
| format | Article |
| id | doaj.art-e11982d57dfd42e98531ccddd7023b82 |
| institution | Directory Open Access Journal |
| issn | 2076-2607 |
| language | English |
| last_indexed | 2024-03-10T22:27:30Z |
| publishDate | 2023-08-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Microorganisms |
| spelling | doaj.art-e11982d57dfd42e98531ccddd7023b822023-11-19T12:00:58ZengMDPI AGMicroorganisms2076-26072023-08-01119213110.3390/microorganisms11092131Pyrenebutyrate Enhances the Antibacterial Effect of Peptide-Coupled Antisense Peptide Nucleic Acids in <i>Streptococcus pyogenes</i>Corina Abt0Lisa Marie Gerlach1Jana Bull2Anette Jacob3Bernd Kreikemeyer4Nadja Patenge5Institute of Medical Microbiology, Virology and Hygiene, University Medicine Rostock, 18057 Rostock, GermanyInstitute of Medical Microbiology, Virology and Hygiene, University Medicine Rostock, 18057 Rostock, GermanyInstitute of Medical Microbiology, Virology and Hygiene, University Medicine Rostock, 18057 Rostock, GermanyPeps4LS GmbH, 69120 Heidelberg, GermanyInstitute of Medical Microbiology, Virology and Hygiene, University Medicine Rostock, 18057 Rostock, GermanyInstitute of Medical Microbiology, Virology and Hygiene, University Medicine Rostock, 18057 Rostock, GermanyAntisense peptide nucleic acids (PNAs) inhibit bacterial growth in several infection models. Since PNAs are not spontaneously taken up by bacteria, they are often conjugated to carriers such as cell-penetrating peptides (CPPs) in order to improve translocation. Hydrophobic counterions such as pyrenebutyrate (PyB) have been shown to facilitate translocation of peptides over natural and artificial membranes. In this study, the capability of PyB to support translocation of CPP-coupled antisense PNAs into bacteria was investigated in <i>Streptococcus pyogenes</i> and <i>Streptococcus pneumoniae</i>. PyB enhanced the antimicrobial activity of CPP-conjugated antisense PNAs in <i>S. pyogenes</i>. The most significant effect of PyB was observed in combination with K8-conjugated anti-<i>gyrA</i> PNAs. In contrast, no significant effect of PyB on the antimicrobial activity of CPP-conjugated PNAs in <i>S. pneumoniae</i> was detected. Uptake of K8-FITC into <i>S. pyogenes</i>, <i>Escherichia coli</i>, and <i>Klebsiella pneumoniae</i> could be improved by pre-incubation with PyB, indicating that PyB supports the antimicrobial effect of CPP-antisense PNAs in <i>S. pyogenes</i> by facilitating the translocation of peptides across the bacterial membrane.https://www.mdpi.com/2076-2607/11/9/2131pyrenebutyrateantimicrobial activityantimicrobial therapyantisense molecules<i>Streptococcus pyogenes</i><i>Streptococcus pneumoniae</i> |
| spellingShingle | Corina Abt Lisa Marie Gerlach Jana Bull Anette Jacob Bernd Kreikemeyer Nadja Patenge Pyrenebutyrate Enhances the Antibacterial Effect of Peptide-Coupled Antisense Peptide Nucleic Acids in <i>Streptococcus pyogenes</i> Microorganisms pyrenebutyrate antimicrobial activity antimicrobial therapy antisense molecules <i>Streptococcus pyogenes</i> <i>Streptococcus pneumoniae</i> |
| title | Pyrenebutyrate Enhances the Antibacterial Effect of Peptide-Coupled Antisense Peptide Nucleic Acids in <i>Streptococcus pyogenes</i> |
| title_full | Pyrenebutyrate Enhances the Antibacterial Effect of Peptide-Coupled Antisense Peptide Nucleic Acids in <i>Streptococcus pyogenes</i> |
| title_fullStr | Pyrenebutyrate Enhances the Antibacterial Effect of Peptide-Coupled Antisense Peptide Nucleic Acids in <i>Streptococcus pyogenes</i> |
| title_full_unstemmed | Pyrenebutyrate Enhances the Antibacterial Effect of Peptide-Coupled Antisense Peptide Nucleic Acids in <i>Streptococcus pyogenes</i> |
| title_short | Pyrenebutyrate Enhances the Antibacterial Effect of Peptide-Coupled Antisense Peptide Nucleic Acids in <i>Streptococcus pyogenes</i> |
| title_sort | pyrenebutyrate enhances the antibacterial effect of peptide coupled antisense peptide nucleic acids in i streptococcus pyogenes i |
| topic | pyrenebutyrate antimicrobial activity antimicrobial therapy antisense molecules <i>Streptococcus pyogenes</i> <i>Streptococcus pneumoniae</i> |
| url | https://www.mdpi.com/2076-2607/11/9/2131 |
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