Antibacterial Peptide Nucleic Acid-Antimicrobial Peptide (PNA-AMP) Conjugates: Antisense Targeting of Fatty Acid Biosynthesis

Anna Mette Hansen; Gitte Bonke; Camilla Josephine Larsen; Niloofar Yavari; Peter E. Nielsen; Henrik Franzyk

doi:10.1021/acs.bioconjchem.6b00013

Antibacterial Peptide Nucleic Acid-Antimicrobial Peptide (PNA-AMP) Conjugates: Antisense Targeting of Fatty Acid Biosynthesis

Anna Mette Hansen, Gitte Bonke, Camilla Josephine Larsen, Niloofar Yavari, Peter E. Nielsen, Henrik Franzyk

39 Citations (Scopus)

Abstract

Antisense peptide nucleic acid (PNA) oligomers constitute a novel class of potential antibiotics that inhibit bacterial growth via specific knockdown of essential gene expression. However, discovery of efficient, nontoxic delivery vehicles for such PNA oligomers has remained a challenge. In the present study we show that antimicrobial peptides (AMPs) with an intracellular mode of action can be efficient vehicles for bacterial delivery of an antibacterial PNA targeting the essential acpP gene. The results demonstrate that buforin 2-A (BF2-A), drosocin, oncocin 10, Pep-1-K, KLW-9,13-a, (P59→W59)-Tat48-60, BF-2A-RXR, and drosocin-RXR are capable of transporting PNA effectively into E. coli (MICs of 1-4 μM). Importantly, presence of the inner-membrane peptide transporter SbmA was not required for antibacterial activity of PNA-AMP conjugates containing Pep-1-K, KLW-9,13-a, or drosocin-RXR (MICs of 2-4 μM). (Figure Presented).

Original language	English
Journal	Bioconjugate Chemistry
Volume	27
Issue number	4
Pages (from-to)	863-867
Number of pages	5
ISSN	1043-1802
DOIs	https://doi.org/10.1021/acs.bioconjchem.6b00013
Publication status	Published - 20 Apr 2016

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@article{6b396019a1ca46adb3de7ced4d47330c,

title = "Antibacterial Peptide Nucleic Acid-Antimicrobial Peptide (PNA-AMP) Conjugates: Antisense Targeting of Fatty Acid Biosynthesis",

abstract = "Antisense peptide nucleic acid (PNA) oligomers constitute a novel class of potential antibiotics that inhibit bacterial growth via specific knockdown of essential gene expression. However, discovery of efficient, nontoxic delivery vehicles for such PNA oligomers has remained a challenge. In the present study we show that antimicrobial peptides (AMPs) with an intracellular mode of action can be efficient vehicles for bacterial delivery of an antibacterial PNA targeting the essential acpP gene. The results demonstrate that buforin 2-A (BF2-A), drosocin, oncocin 10, Pep-1-K, KLW-9,13-a, (P59→W59)-Tat48-60, BF-2A-RXR, and drosocin-RXR are capable of transporting PNA effectively into E. coli (MICs of 1-4 μM). Importantly, presence of the inner-membrane peptide transporter SbmA was not required for antibacterial activity of PNA-AMP conjugates containing Pep-1-K, KLW-9,13-a, or drosocin-RXR (MICs of 2-4 μM). (Figure Presented).",

author = "Hansen, {Anna Mette} and Gitte Bonke and Larsen, {Camilla Josephine} and Niloofar Yavari and Nielsen, {Peter E.} and Henrik Franzyk",

year = "2016",

month = apr,

day = "20",

doi = "10.1021/acs.bioconjchem.6b00013",

language = "English",

volume = "27",

pages = "863--867",

journal = "Bioconjugate Chemistry",

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publisher = "American Chemical Society",

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TY - JOUR

T1 - Antibacterial Peptide Nucleic Acid-Antimicrobial Peptide (PNA-AMP) Conjugates

T2 - Antisense Targeting of Fatty Acid Biosynthesis

AU - Hansen, Anna Mette

AU - Bonke, Gitte

AU - Larsen, Camilla Josephine

AU - Yavari, Niloofar

AU - Nielsen, Peter E.

AU - Franzyk, Henrik

PY - 2016/4/20

Y1 - 2016/4/20

N2 - Antisense peptide nucleic acid (PNA) oligomers constitute a novel class of potential antibiotics that inhibit bacterial growth via specific knockdown of essential gene expression. However, discovery of efficient, nontoxic delivery vehicles for such PNA oligomers has remained a challenge. In the present study we show that antimicrobial peptides (AMPs) with an intracellular mode of action can be efficient vehicles for bacterial delivery of an antibacterial PNA targeting the essential acpP gene. The results demonstrate that buforin 2-A (BF2-A), drosocin, oncocin 10, Pep-1-K, KLW-9,13-a, (P59→W59)-Tat48-60, BF-2A-RXR, and drosocin-RXR are capable of transporting PNA effectively into E. coli (MICs of 1-4 μM). Importantly, presence of the inner-membrane peptide transporter SbmA was not required for antibacterial activity of PNA-AMP conjugates containing Pep-1-K, KLW-9,13-a, or drosocin-RXR (MICs of 2-4 μM). (Figure Presented).

AB - Antisense peptide nucleic acid (PNA) oligomers constitute a novel class of potential antibiotics that inhibit bacterial growth via specific knockdown of essential gene expression. However, discovery of efficient, nontoxic delivery vehicles for such PNA oligomers has remained a challenge. In the present study we show that antimicrobial peptides (AMPs) with an intracellular mode of action can be efficient vehicles for bacterial delivery of an antibacterial PNA targeting the essential acpP gene. The results demonstrate that buforin 2-A (BF2-A), drosocin, oncocin 10, Pep-1-K, KLW-9,13-a, (P59→W59)-Tat48-60, BF-2A-RXR, and drosocin-RXR are capable of transporting PNA effectively into E. coli (MICs of 1-4 μM). Importantly, presence of the inner-membrane peptide transporter SbmA was not required for antibacterial activity of PNA-AMP conjugates containing Pep-1-K, KLW-9,13-a, or drosocin-RXR (MICs of 2-4 μM). (Figure Presented).

U2 - 10.1021/acs.bioconjchem.6b00013

DO - 10.1021/acs.bioconjchem.6b00013

M3 - Journal article

C2 - 26938833

SN - 1043-1802

VL - 27

SP - 863

EP - 867

JO - Bioconjugate Chemistry

JF - Bioconjugate Chemistry

IS - 4

ER -

Antibacterial Peptide Nucleic Acid-Antimicrobial Peptide (PNA-AMP) Conjugates: Antisense Targeting of Fatty Acid Biosynthesis

Abstract

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