Peptide Nucleic Acid Antisense Oligomer as a Therapeutic Strategy against Bacterial Infection: Proof of Principle Using Mouse Intraperitoneal Infection

Variations in Amino Acid Composition of Antisense Peptide-Phosphorodiamidate Morpholino Oligomer Affect Potency against Escherichia coli In Vitro and In Vivo

“…When antisense oligomers are added to pure bacterial cultures, they have been shown to decrease the levels of expression of reporter genes such as luciferase (5,7), activate endogenous genes such as ␤-galactosidase (7), or inhibit growth by targeting essential genes or RNA (9,10,11,14,23,28). In addition, antisense oligomers reduce infection and increase the survival of mice infected with Escherichia coli (8,21,22).…”

Antisense Antibacterials: From Proof-Of-Concept to Therapeutic Perspectives

“…Validated essential genes among different bacterial species include fbpA/ fbpB/fbpC (Harth & et al, 2002(Harth & et al, , 2007 and glnA1 (Harth & et al, 2000) in Mycobacterium tuberculosis, gyrA/ompA in Klebsiella pneumonia (Kurupati & et al, 2007), inhA in Mycobacterium smegmatis (Kulyte & et al, 2005), oxyR/ahpC in Mycobacterium avium (Shimizu & et al, 2003), NPT/EhErd2 in Entamoeba histolytica (Stock & et al, 2000(Stock & et al, , 2001, gtfB in Streptococcus mutans (Guo & et al, 2006), fmhB/ gyrA/hmrB (Nekhotiaeva & et al, 2004a) and fabI (Ji & et al, 2004) in Staphylococcus aureus, 23S rRNA (Xue-Wen & et al, 2007), 16S rRNA plus lacZ/bla (Good & Nielsen, 1998), and RNAse P (Gruegelsiepe & et al, 2006) in Escherichia coli, and acpP in Burkholderia cepacia (Greenberg & et al, 2010), Escherichia coli (Deere & et al, 2005b;Geller & et al, 2003aGeller & et al, , 2003bGeller & et al, , 2005Mellbye & et al, 2009Mellbye & et al, , 2010Tan & et al, 2005;Tilley & et al, 2007) as well as Salmonella enterica serovar Typhimurium (Mitev & et al, 2009;Tilley & et al, 2006). Mellbye et al, First proof-of-principle evidence was given by White et al in 1997 for successful increasing the bactericidal activity of norfloxacin by antisense inhibiting the marRAB operon in Escherichia coli (White & et al, 1997).…”

Peptide nucleic acid antisense oligomers open an avenue for developing novel antibacterial molecules

“…It has been shown that PNA or Morpholino antisense oligomers in conjugation with (KFF)3K, (RX)6B-, (RXR)4XB-, and (RFR)4XB peptides are able to eliminate bacterial infection in mice [18,[24][25][26]. Furthermore, it is also possible that the peptides which efficiently transport PNA oligomers in mammalian cells may also be capable of transporting PNA oligomers in bacteria [27,28].…”