Pyrenebutyrate Enhances the Antibacterial Effect of Peptide-Coupled Antisense Peptide Nucleic Acids in Streptococcus pyogenes

被引：4

作者：

Abt, Corina ^{[1
]}

Gerlach, Lisa Marie ^{[1
]}

Bull, Jana ^{[1
]}

Jacob, Anette ^{[2
]}

Kreikemeyer, Bernd ^{[1
]}

Patenge, Nadja ^{[1
]}

机构：

[1] Univ Hosp Rostock, Inst Med Microbiol Virol & Hyg, D-18057 Rostock, Germany

[2] Peps4LS GmbH, D-69120 Heidelberg, Germany

来源：

MICROORGANISMS | 2023年 / 11卷 / 09期

关键词：

pyrenebutyrate; antimicrobial activity; antimicrobial therapy; antisense molecules; Streptococcus pyogenes; Streptococcus pneumoniae; Escherichia coli; Klebsiella pneumoniae; peptide nucleic acid; PNA; cell-penetrating peptide; CPP; CELL-PENETRATING PEPTIDES; GENE-EXPRESSION; INHIBITION; PNEUMONIAE; CAPSULE; MODEL; TRANSLOCATION; MEMBRANES; LIQUID; GROWTH;

D O I：

10.3390/microorganisms11092131

中图分类号：

Q93 [微生物学];

学科分类号：

071005 ; 100705 ;

摘要：

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 Streptococcus pyogenes and Streptococcus pneumoniae. PyB enhanced the antimicrobial activity of CPP-conjugated antisense PNAs in S. pyogenes. The most significant effect of PyB was observed in combination with K8-conjugated anti-gyrA PNAs. In contrast, no significant effect of PyB on the antimicrobial activity of CPP-conjugated PNAs in S. pneumoniae was detected. Uptake of K8-FITC into S. pyogenes, Escherichia coli, and Klebsiella pneumoniae could be improved by pre-incubation with PyB, indicating that PyB supports the antimicrobial effect of CPP-antisense PNAs in S. pyogenes by facilitating the translocation of peptides across the bacterial membrane.

引用

页数：12