Effects of Lipidation on a Proline-Rich Antibacterial Peptide
The emergence of multidrug-resistant bacteria is a worldwide health problem. Antimicrobial peptides have been recognized as potential alternatives to conventional antibiotics, but still require optimization. The proline-rich antimicrobial peptide Bac7(1-16) is active against only a limited number of...
| Main Authors: | , , , , , |
|---|---|
| Format: | Article |
| Published: |
Multidisciplinary Digital Publishing Institute
2021
|
| Online Access: | https://hdl.handle.net/1721.1/133210 |
| _version_ | 1811093326168850432 |
|---|---|
| author | Armas, Federica Di Stasi, Adriana Mardirossian, Mario Romani, Antonello A. Benincasa, Monica Scocchi, Marco |
| author_facet | Armas, Federica Di Stasi, Adriana Mardirossian, Mario Romani, Antonello A. Benincasa, Monica Scocchi, Marco |
| author_sort | Armas, Federica |
| collection | MIT |
| description | The emergence of multidrug-resistant bacteria is a worldwide health problem. Antimicrobial peptides have been recognized as potential alternatives to conventional antibiotics, but still require optimization. The proline-rich antimicrobial peptide Bac7(1-16) is active against only a limited number of Gram-negative bacteria. It kills bacteria by inhibiting protein synthesis after its internalization, which is mainly supported by the bacterial transporter SbmA. In this study, we tested two different lipidated forms of Bac7(1-16) with the aim of extending its activity against those bacterial species that lack SbmA. We linked a C12-alkyl chain or an ultrashort cationic lipopeptide Lp-I to the C-terminus of Bac7(1-16). Both the lipidated Bac-C12 and Bac-Lp-I forms acquired activity at low micromolar MIC values against several Gram-positive and Gram-negative bacteria. Moreover, unlike Bac7(1-16), Bac-C12, and Bac-Lp-I did not select resistant mutants in <i>E. coli</i> after 14 times of exposure to sub-MIC concentrations of the respective peptide. We demonstrated that the extended spectrum of activity and absence of de novo resistance are likely related to the acquired capability of the peptides to permeabilize cell membranes. These results indicate that C-terminal lipidation of a short proline-rich peptide profoundly alters its function and mode of action and provides useful insights into the design of novel broad-spectrum antibacterial agents. |
| first_indexed | 2024-09-23T15:43:28Z |
| format | Article |
| id | mit-1721.1/133210 |
| institution | Massachusetts Institute of Technology |
| last_indexed | 2024-09-23T15:43:28Z |
| publishDate | 2021 |
| publisher | Multidisciplinary Digital Publishing Institute |
| record_format | dspace |
| spelling | mit-1721.1/1332102021-11-01T14:36:56Z Effects of Lipidation on a Proline-Rich Antibacterial Peptide Armas, Federica Di Stasi, Adriana Mardirossian, Mario Romani, Antonello A. Benincasa, Monica Scocchi, Marco The emergence of multidrug-resistant bacteria is a worldwide health problem. Antimicrobial peptides have been recognized as potential alternatives to conventional antibiotics, but still require optimization. The proline-rich antimicrobial peptide Bac7(1-16) is active against only a limited number of Gram-negative bacteria. It kills bacteria by inhibiting protein synthesis after its internalization, which is mainly supported by the bacterial transporter SbmA. In this study, we tested two different lipidated forms of Bac7(1-16) with the aim of extending its activity against those bacterial species that lack SbmA. We linked a C12-alkyl chain or an ultrashort cationic lipopeptide Lp-I to the C-terminus of Bac7(1-16). Both the lipidated Bac-C12 and Bac-Lp-I forms acquired activity at low micromolar MIC values against several Gram-positive and Gram-negative bacteria. Moreover, unlike Bac7(1-16), Bac-C12, and Bac-Lp-I did not select resistant mutants in <i>E. coli</i> after 14 times of exposure to sub-MIC concentrations of the respective peptide. We demonstrated that the extended spectrum of activity and absence of de novo resistance are likely related to the acquired capability of the peptides to permeabilize cell membranes. These results indicate that C-terminal lipidation of a short proline-rich peptide profoundly alters its function and mode of action and provides useful insights into the design of novel broad-spectrum antibacterial agents. 2021-10-27T18:49:53Z 2021-10-27T18:49:53Z 2021-07-26 2021-08-06T15:19:20Z Article http://purl.org/eprint/type/JournalArticle https://hdl.handle.net/1721.1/133210 International Journal of Molecular Sciences 22 (15): 7959 (2021) PUBLISHER_CC http://dx.doi.org/10.3390/ijms22157959 Creative Commons Attribution https://creativecommons.org/licenses/by/4.0/ application/pdf Multidisciplinary Digital Publishing Institute Multidisciplinary Digital Publishing Institute |
| spellingShingle | Armas, Federica Di Stasi, Adriana Mardirossian, Mario Romani, Antonello A. Benincasa, Monica Scocchi, Marco Effects of Lipidation on a Proline-Rich Antibacterial Peptide |
| title | Effects of Lipidation on a Proline-Rich Antibacterial Peptide |
| title_full | Effects of Lipidation on a Proline-Rich Antibacterial Peptide |
| title_fullStr | Effects of Lipidation on a Proline-Rich Antibacterial Peptide |
| title_full_unstemmed | Effects of Lipidation on a Proline-Rich Antibacterial Peptide |
| title_short | Effects of Lipidation on a Proline-Rich Antibacterial Peptide |
| title_sort | effects of lipidation on a proline rich antibacterial peptide |
| url | https://hdl.handle.net/1721.1/133210 |
| work_keys_str_mv | AT armasfederica effectsoflipidationonaprolinerichantibacterialpeptide AT distasiadriana effectsoflipidationonaprolinerichantibacterialpeptide AT mardirossianmario effectsoflipidationonaprolinerichantibacterialpeptide AT romaniantonelloa effectsoflipidationonaprolinerichantibacterialpeptide AT benincasamonica effectsoflipidationonaprolinerichantibacterialpeptide AT scocchimarco effectsoflipidationonaprolinerichantibacterialpeptide |