Prevention of lethal murine candidiasis using HP (2–20), an antimicrobial peptide derived from the N-terminus of Helicobacter pylori ribosomal protein L1

Peptide HP (2–20), A 2KKVFKRLEKLFSKIQNDK 20 , is a cationic antimicrobial peptide derived from the N-terminus of Helicobacter pylori ribosomal protein 1, HpRpL1. Native peptide HP (2–20) and its synthetic derivatives have been shown in vitro to exhibit potent killing activity against Gram-positive, Gram-negative and yeast cells, thus, making them promising candidates for treatment of polymicrobial infections. However, the therapeutic potential of peptide HP (2–20) or its synthetic derivatives in any animal model of either bacterial or fungal diseases has not yet been investigated. In this study, we demonstrate that synthetic peptide amide HP (2–20), administered in six doses (300 μg each; one intraperitoneal dose at the time of the infection, followed by five intravenous doses at 12 h intervals) to CBA/J male mice experimentally infected with a lethal inoculum (1×10 9 CFU) of Candida albicans, delayed the onset of disease, suppressed disease progression, and greatly increased survival rate and time (16.6% by day 14), as compared with the untreated infected control mice (100% mortality by day 5). Further, using isotonic buffer systems differing in ionic strength, peptide HP (2–20) was shown in vitro to exhibit an ionic strength-dependent hemolytic activity, previously not detected. Repeated intravenous administration of uninfected control CBA/J male mice with peptide HP (2–20), however, caused neither morbidity nor mortality. These findings strongly evidence the therapeutic efficacy and safety values of peptide HP (2–20) as a lead drug for the treatment of acquired candidiasis.