In view of the global spread of multiresistant bacteria and the occurrence of panresistant
bacteria, there is an urgent need for antimicrobials with novel modes of action. A promising class is
antimicrobial peptides (AMPs), including them proline-rich AMPs (PrAMPs), which target the 70S
ribosome to inhibit protein translation. Here, we present a new designer peptide, Api805, combining
the N- and C-terminal sequences of PrAMPs Api137 and drosocin, respectively. Api805 was similarly
active against two Escherichia coli B strains but was inactive against E. coli K12 strain BW25113. These
different activities could not be explained by the dissociation constants measured for 70S ribosome
preparations from E. coli K12 and B strains. Mutations in the SbmA transporter that PrAMPs use to
pass the inner membrane or proteolytic degradation of Api805 by lysate proteases could not explain
this either. Interestingly, Api805 seems not to bind to the known binding sites of PrAMPs at the
70S ribosome and inhibited in vitro protein translation, independent of release factors, most likely
using a “multimodal effect”. Interestingly, Api805 entered the E. coli B strain Rosetta faster and at
larger quantities than the E. coli K-12 strain BW25113, which may be related to the different LPS core
structure. In conclusion, slight structural changes in PrAMPs significantly altered their binding sites
and mechanisms of action, allowing for the design of different antibiotic classes.
| Identifer | oai:union.ndltd.org:DRESDEN/oai:qucosa:de:qucosa:86003 |
| Date | 13 June 2023 |
| Creators | Ludwig, Tobias, Kriszan, Andor, Mohammed, Gubran Khalil, Hoffmann, Ralf |
| Publisher | MDPI |
| Source Sets | Hochschulschriftenserver (HSSS) der SLUB Dresden |
| Language | English |
| Detected Language | English |
| Type | info:eu-repo/semantics/publishedVersion, doc-type:article, info:eu-repo/semantics/article, doc-type:Text |
| Rights | info:eu-repo/semantics/openAccess |
| Relation | 430 |
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