2016
DOI: 10.1093/jac/dkw384
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Antimicrobial activity of antisense peptide–peptide nucleic acid conjugates against non-typeableHaemophilus influenzaein planktonic and biofilm forms

Abstract: Background: Antisense peptide nucleic acids (PNAs) are synthetic polymers that mimic DNA/RNA and inhibit bacterial gene expression in a sequence-specific manner.Methods: To assess activity against non-typeable Haemophilus influenzae (NTHi), we designed six PNA-peptides that target acpP, encoding an acyl carrier protein. MICs and minimum biofilm eradication concentrations (MBECs) were determined. Resistant strains were selected by serial passages on media with a sub-MIC concentration of acpP-PNA.Results: The MI… Show more

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Cited by 31 publications
(20 citation statements)
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“…PS-ASO simultaneously targeting two glucosyltransferases inhibited Streptococcus mutans biofilm formation in vitro (Kalesinskas et al 2015). A (KFF)3K-PNA targeting acpP had significant activity against biofilm forms of non-typeable Haemophilus influenzae (Otsuka et al 2017). PPMO targeting acpP was effective at both preventing P. aeruginosa PAO1 biofilm formation and at reducing existing biofilms (Howard et al 2017).…”
Section: Targeting Antibiotic Resistancementioning
confidence: 99%
“…PS-ASO simultaneously targeting two glucosyltransferases inhibited Streptococcus mutans biofilm formation in vitro (Kalesinskas et al 2015). A (KFF)3K-PNA targeting acpP had significant activity against biofilm forms of non-typeable Haemophilus influenzae (Otsuka et al 2017). PPMO targeting acpP was effective at both preventing P. aeruginosa PAO1 biofilm formation and at reducing existing biofilms (Howard et al 2017).…”
Section: Targeting Antibiotic Resistancementioning
confidence: 99%
“…Specifically, the (KFF) 3 K peptide conjugated to a PNA targeting the essential bacterial gene, acpP , was shown to be sequence specifically bactericidal against Escherichia coli (Good et al, 2001). Subsequently, antibacterial effects of peptide-PNA [and also of phosphordiamidate morpholino oligomer (PMO) (Geller et al, 2018)] conjugates against a range of antibiotic resistant bacterial species have been reported, e.g., multi-resistant Klebsiella pneumoniae (Kurupati et al, 2007) and Haemophilus influenzae (Otsuka et al, 2017), and Pseudomonas aeruginosa (Montagner et al, 2017) in planktonic cultures as well as biofilms. Furthermore, recent studies have identified the inner-membrane SbmA protein as a necessary transporter of some peptide-PNA conjugates (Ghosal et al, 2013).…”
Section: Introductionmentioning
confidence: 99%
“…Peptide nucleic acids (PNA) present an antisense strategy that offer advantages in stability 15,16 , binding strength 17 , and mismatch discrimination compared to similar technologies 18 . Prior research from our lab and others have demonstrated the utility of PNA as an antibiotic platform [19][20][21][22][23][24] .…”
mentioning
confidence: 98%