title: Human-β-defensins-1-3 and analogs do not require proton motive force for antibacterial activity against Escherichia coli.
abstract: Human-β-defensins 1-3 (HBD-1-3) and their C-terminal analogs Phd-1-3 do not show antibacterial activity against Escherichia coli in the presence of mono- and divalent cations. Activity of peptides was examined against E. coli pretreated with carbonyl cyanide m-chlorophenylhydrazone (CCCP) and salt remedial Escherichia coli ftsEX, a deletion mutant of FtsEX complex [an ATP-binding cassette (ABC) transporter protein], in the presence of Na(+), Ca(2+), and Mg(2+). Activity was observed in the presence of Na(+) and Ca(2+), although not in the presence of Mg(2+) against E. coli, when proton motive force (PMF) was dissipated by CCCP. The peptides exhibited antibacterial activity against E. coli ftsEX even in the presence of Na(+) and Ca(2+). Our results indicate that HBD-1-3 and Phd-1-3 do not require PMF for their antibacterial activity. The absence of activity against E. coli in the presence of Na(+) and Ca(2+) ions is due to not only weakened electrostatic interactions with anionic membrane components, but also involvement of electrochemical gradients. However, Mg(2+) prevents electrostatic interaction of the peptides with the outer membrane resulting in loss of activity.
authors: CSIR - Centre for Cellular and Molecular Biology, Hyderabad, India.
authors: Viswanatha
authors: V
authors: Krishnakumari
authors: Kavin K
authors: KK
authors: Packiyanathan
authors: Ramakrishnan
authors: R
authors: Nagaraj
mesh_terms: D000890:Anti-Infective Agents / Q000378:metabolism*; D002413:Cations, Divalent / Q000378:metabolism; D004926:Escherichia coli / Q000187:drug effects* / Q000378:metabolism; D006801:Humans; D008274:Magnesium / Q000378:metabolism; D008826:Microbial Sensitivity Tests; D018892:Proton-Motive Force; D023083:beta-Defensins / Q000378:metabolism*
chemical_list: D000890:Anti-Infective Agents; D002413:Cations, Divalent; C406407:DEFB1 protein, human; C422950:DEFB103A protein, human; C106641:DEFB4A protein, human; D023083:beta-Defensins; D008274:Magnesium
keywords: antibacterial activity; carbonyl cyanide m-chlorophenylhydrazone; human-β-defensins; mono- and divalent cations; proton motive force; β-defensins analogs