Bacterium-Derived Cell-Penetrating Peptides Deliver Gentamicin To Kill Intracellular Pathogens

Overview

Journal Antimicrob Agents Chemother

Publisher American Society for Microbiology

Specialty Pharmacology

Date 2017 Jan 19

PMID 28096156

Citations 25

Authors

Marta Gomarasca

Thaynan F C Martins

Lilo Greune

Philip R Hardwidge

M Alexander Schmidt

Christian Ruter

Affiliations

Soon will be listed here.

Abstract

Commonly used antimicrobials show poor cellular uptake and often have limited access to intracellular targets, resulting in low antimicrobial activity against intracellular pathogens. An efficient delivery system to transport these drugs to the intracellular site of action is needed. Cell-penetrating peptides (CPPs) mediate the internalization of biologically active molecules into the cytoplasm. Here, we characterized two CPPs, α1H and α2H, derived from the YopM effector protein. These CPPs, as well as Tat (-activator of transcription) from HIV-1, were used to deliver the antibiotic gentamicin to target intracellular bacteria. The YopM-derived CPPs penetrated different endothelial and epithelial cells to the same extent as Tat. CPPs were covalently conjugated to gentamicin, and CPP-gentamicin conjugates were used to target infected cells to kill multiple intracellular Gram-negative pathogenic bacteria, including K1, serovar Typhimurium, and Taken together, CPPs show great potential as delivery vehicles for antimicrobial agents and may contribute to the generation of new therapeutic tools to treat infectious diseases caused by intracellular pathogens.

Citing Articles

Dual Antibiotic Approach: Synthesis and Antibacterial Activity of Antibiotic-Antimicrobial Peptide Conjugates.

Bellucci M, Romani C, Sani M, Volonterio A Antibiotics (Basel). 2024; 13(8).

PMID: 39200083 PMC: 11352213. DOI: 10.3390/antibiotics13080783.

TriplEP-CPP: Algorithm for Predicting the Properties of Peptide Sequences.

Serebrennikova M, Grafskaia E, Maltsev D, Ivanova K, Bashkirov P, Kornilov F Int J Mol Sci. 2024; 25(13).

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Intracellular bacteria in cancer-prospects and debates.

Schorr L, Mathies M, Elinav E, Puschhof J NPJ Biofilms Microbiomes. 2023; 9(1):76.

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Antimicrobial peptides´ immune modulation role in intracellular bacterial infection.

Duarte-Mata D, Salinas-Carmona M Front Immunol. 2023; 14:1119574.

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Antimicrobial and Cell-Penetrating Peptides: Understanding Penetration for the Design of Novel Conjugate Antibiotics.

Hadjicharalambous A, Bournakas N, Newman H, Skynner M, Beswick P Antibiotics (Basel). 2022; 11(11).

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