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(2)KKVFKRLEKLFSKIQNDK(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 (300microg each; one intraperitoneal dose at the time of the infection, followed by five intravenous doses at 12h intervals) to CBA/J male mice experimentally infected with a lethal inoculum ( [Formula: see text] 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.
Ribeiro
Patrícia Damasceno
PD
Laboratório de Biotecnologia, Centro de Biociências e Biotecnologia, Universidade Estadual do Norte Fluminense Darcy Ribeiro, Avenida Alberto Lamego 2000, Parque Califórnia, Campos dos Goytacazes, CEP 28013-602, RJ, Brazil.
Medina-Acosta
Enrique
E
D000818:Animals; D000935:Antifungal Agents / Q000009:adverse effects / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use*; D001426:Bacterial Proteins / Q000009:adverse effects / Q000737:chemistry* / Q000494:pharmacology / Q000627:therapeutic use*; D002177:Candidiasis / Q000382:microbiology / Q000517:prevention & control*; D004305:Dose-Response Relationship, Drug; D004912:Erythrocytes / Q000187:drug effects; D016480:Helicobacter pylori / Q000737:chemistry*; D006461:Hemolysis / Q000187:drug effects; D006801:Humans; D051379:Mice; D008815:Mice, Inbred Strains; D009994:Osmolar Concentration; D010446:Peptide Fragments / Q000009:adverse effects / Q000737:chemistry* / Q000494:pharmacology / Q000627:therapeutic use*; D012269:Ribosomal Proteins / Q000737:chemistry*; D015996:Survival Rate; D015003:Yeasts / Q000187:drug effects / Q000254:growth & development
D000935:Antifungal Agents; D001426:Bacterial Proteins; C433783:Hp (2-20) protein, Helicobacter pylori; D010446:Peptide Fragments; D012269:Ribosomal Proteins; C028546:ribosomal protein L1