Mechanisms of adrenomedullin antimicrobial action.
The mechanism of antimicrobial action of the multifunctional peptide adrenomedullin (AM) against Escherichia coli and Staphylococcus aureus was investigated. AM (52 residues) and AM fragments (1-12, 1-21, 13-52, 16-21, 16-52, 22-52, 26-52 and 34-52 residues) were tested for activity. Carboxy-terminal fragments were shown to be up to 250-fold more active than the parent molecule. Minimum inhibitory concentration values of the most active fragments (13-52 and 16-52) and the parent molecule were 4.9 x 10(-2) and 12.5 microg/ml, respectively, with E. coli. Ultrastructural analyses of AM treated cells demonstrated marked cell wall disruption with E. coli within 0.5 h. Abnormal septum formation with no apparent peripheral cell wall disruption was observed with S. aureus after 2 h. Outer membrane permeabilisation assays with E. coli confirmed that the C-terminal fragments were significantly (P < 0.05) more active. It is suggested that postsecretory processing may generate multiple AM congeners that have enhanced antimicrobial activities against a range of potential targets.
Allaker
Robert P
RP
Oral Microbiology, Institute of Cell and Molecular Science, Queen Mary, University of London, Newark Street, London E1 2AT, UK. R.P.Allaker@qmul.ac.uk
Grosvenor
Paul W
PW
McAnerney
David C
DC
Sheehan
Barry E
BE
Srikanta
Bakula H
BH
Pell
Keith
K
Kapas
Supriya
S
D053607:Adrenomedullin; D000890:Anti-Infective Agents / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology*; D004926:Escherichia coli / Q000187:drug effects; D008826:Microbial Sensitivity Tests; D008854:Microscopy, Electron; D010455:Peptides / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology*; D013211:Staphylococcus aureus / Q000187:drug effects
D000890:Anti-Infective Agents; D010455:Peptides; D053607:Adrenomedullin