De novo-derived cationic antimicrobial peptide activity in a murine model of Pseudomonas aeruginosa bacteraemia.
OBJECTIVE
We describe the antimicrobial activity against Pseudomonas aeruginosa of the de novo-derived antimicrobial peptide WLBU2 in an animal model of infection.


METHODS
For this study, an intravenous (iv) model of P. aeruginosa infection was established. The minimum lethal murine dose of P. aeruginosa strain PA01 was determined to be 3 x 10(7) cfu when bacteria were administered iv. Increasing concentrations of WLBU2 were instilled either prior to or following PA01 septic exposure.


RESULTS
For the mice given peptide post-bacterial infection, in the 1 mg/kg group, nine of nine animals died because of Pseudomonas sepsis; in the 3 mg/kg group, only one of nine succumbed to infection and in the 4 mg/kg group, all mice were protected (P < 0.0001). Similar results were obtained when WLBU2 was given 1 h prior to Pseudomonas infection.


CONCLUSIONS
Although the therapeutic window in this model is narrow, the results nonetheless provide encouraging evidence for WLBU2 as a potential prophylactic or treatment of bacterial infection.
Deslouches
Berthony
B
Department of Molecular Genetics and Biochemistry, University of Pittsburgh School of Medicine, Pittsburgh, PA 15261, USA.
Gonzalez
Ivan A
IA
DeAlmeida
Dilhari
D
Islam
Kazi
K
Steele
Chad
C
Montelaro
Ronald C
RC
Mietzner
Timothy A
TA
D000595:Amino Acid Sequence; D000818:Animals; D023181:Antimicrobial Cationic Peptides / Q000302:isolation & purification / Q000494:pharmacology / Q000627:therapeutic use*; D016470:Bacteremia / Q000188:drug therapy* / Q000382:microbiology; D018450:Disease Progression; D051379:Mice; D008969:Molecular Sequence Data; D011552:Pseudomonas Infections / Q000188:drug therapy* / Q000382:microbiology; D018805:Sepsis / Q000382:microbiology / Q000517:prevention & control; D013534:Survival
D023181:Antimicrobial Cationic Peptides; C520840:WLBU2 peptide