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Logo of jcinvestThe Journal of Clinical Investigation
J Clin Invest. 1988 June; 81(6): 1829–1835.
PMCID: PMC442632

Modulation of the in vitro candidacidal activity of human neutrophil defensins by target cell metabolism and divalent cations.


We tested the in vitro susceptibility of Candida albicans to three defensins from human neutrophilic granulocytes (HNP-1, 2, and 3), a homologous defensin from rabbit leukocytes (NP-1), and four unrelated cationic peptides. Although the primary amino acid sequences of HNP-1, 2, and 3 are identical except for a single amino-terminal amino acid alteration, HNP-1 and HNP-2 killed C. albicans but HNP-3 did not. C. albicans blastoconidia were protected from HNP-1 when incubations were performed in the absence of oxygen or in the presence of inhibitors that blocked both of its mitochondrial respiratory pathways. Neither anaerobiosis nor mitochondrial inhibitors substantially protected C. albicans exposed to NP-1, poly-L-arginine, poly-L-lysine, or mellitin. Human neutrophilic granulocyte defensin-mediated candidacidal activity was inhibited by both Mg2+ and Ca2+, and was unaffected by Fe2+. In contrast, Fe2+ inhibited the candidacidal activity of NP-1 and all of the model cationic peptides, whereas Mg2+ inhibited none of them. These data demonstrate that susceptibility of C. albicans to human defensins depends both on the ionic environment and on the metabolic state of the target cell. The latter finding suggests that leukocyte-mediated microbicidal mechanisms may manifest oxygen dependence for reasons unrelated to the production of reactive oxygen intermediates by the leukocyte.

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Selected References

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  • Selsted ME, Harwig SS, Ganz T, Schilling JW, Lehrer RI. Primary structures of three human neutrophil defensins. J Clin Invest. 1985 Oct;76(4):1436–1439. [PMC free article] [PubMed]
  • Rice WG, Ganz T, Kinkade JM, Jr, Selsted ME, Lehrer RI, Parmley RT. Defensin-rich dense granules of human neutrophils. Blood. 1987 Sep;70(3):757–765. [PubMed]
  • Ganz T, Selsted ME, Szklarek D, Harwig SS, Daher K, Bainton DF, Lehrer RI. Defensins. Natural peptide antibiotics of human neutrophils. J Clin Invest. 1985 Oct;76(4):1427–1435. [PMC free article] [PubMed]
  • Daher KA, Selsted ME, Lehrer RI. Direct inactivation of viruses by human granulocyte defensins. J Virol. 1986 Dec;60(3):1068–1074. [PMC free article] [PubMed]
  • Selsted ME, Szklarek D, Lehrer RI. Purification and antibacterial activity of antimicrobial peptides of rabbit granulocytes. Infect Immun. 1984 Jul;45(1):150–154. [PMC free article] [PubMed]
  • Selsted ME, Szklarek D, Ganz T, Lehrer RI. Activity of rabbit leukocyte peptides against Candida albicans. Infect Immun. 1985 Jul;49(1):202–206. [PMC free article] [PubMed]
  • Selsted ME, Brown DM, DeLange RJ, Harwig SS, Lehrer RI. Primary structures of six antimicrobial peptides of rabbit peritoneal neutrophils. J Biol Chem. 1985 Apr 25;260(8):4579–4584. [PubMed]
  • Henry MF, Nyns ED. Cyanide-insensitive respiration. An alternative mitochondrial pathway. Subcell Biochem. 1975 Mar;4(1):1–65. [PubMed]
  • Shepherd MG, Chin CM, Sullivan PA. The alternate respiratory pathway of Candida albicans. Arch Microbiol. 1978 Jan 23;116(1):61–67. [PubMed]
  • Gladstone GP, Walton E. Effect of iron on the bactericidal proteins from rabbit polymorphonuclear leukocytes. Nature. 1970 Aug 22;227(5260):849–851. [PubMed]
  • Babior BM. Oxidants from phagocytes: agents of defense and destruction. Blood. 1984 Nov;64(5):959–966. [PubMed]
  • Grisham MB, Jefferson MM, Melton DF, Thomas EL. Chlorination of endogenous amines by isolated neutrophils. Ammonia-dependent bactericidal, cytotoxic, and cytolytic activities of the chloramines. J Biol Chem. 1984 Aug 25;259(16):10404–10413. [PubMed]
  • Elsbach P, Weiss J. Oxygen-dependent and oxygen-independent mechanisms of microbicidal activity of neutrophils. Immunol Lett. 1985;11(3-4):159–163. [PubMed]
  • Spitznagel JK. Nonoxidative antimicrobial reactions of leukocytes. Contemp Top Immunobiol. 1984;14:283–343. [PubMed]
  • Odeberg H, Olsson I. Antibacterial activity of cationic proteins from human granulocytes. J Clin Invest. 1975 Nov;56(5):1118–1124. [PMC free article] [PubMed]
  • Odeberg H, Olsson I. Mechanisms for the microbicidal activity of cationic proteins of human granulocytes. Infect Immun. 1976 Dec;14(6):1269–1275. [PMC free article] [PubMed]
  • Miller BF, Abrams R, Dorfman A, Klein M. ANTIBACTERIAL PROPERTIES OF PROTAMINE AND HISTONE. Science. 1942 Nov 6;96(2497):428–430. [PubMed]
  • SELA M, KATCHALSKI E. Biological properties of poly-alpha-amino acids. Adv Protein Chem. 1959;14:391–478. [PubMed]
  • Olson VL, Hansing RL, McClary DO. The role of metabolic energy in the lethal action of basic proteins on Candida albicans. Can J Microbiol. 1977 Feb;23(2):166–174. [PubMed]
  • Svihla G, Dainko JL, Schlenk F. Ultraviolet micrography of penetration of exogenous cytochrome c into the yeast cell. J Bacteriol. 1969 Oct;100(1):498–504. [PMC free article] [PubMed]
  • Yphantis DA, Dainko JL, Schlenk F. Effect of some proteins on the yeast cell membrane. J Bacteriol. 1967 Nov;94(5):1509–1515. [PMC free article] [PubMed]
  • Lehrer RI, Cline MJ. Leukocyte myeloperoxidase deficiency and disseminated candidiasis: the role of myeloperoxidase in resistance to Candida infection. J Clin Invest. 1969 Aug;48(8):1478–1488. [PMC free article] [PubMed]
  • Lehrer RI. Functional aspects of a second mechanism of candidacidal activity by human neutrophils. J Clin Invest. 1972 Oct;51(10):2566–2572. [PMC free article] [PubMed]
  • Lehrer RI, Ladra KM, Hake RB. Nonoxidative fungicidal mechanisms of mammalian granulocytes: demonstration of components with candidacidal activity in human, rabbit, and guinea pig leukocytes. Infect Immun. 1975 Jun;11(6):1226–1234. [PMC free article] [PubMed]
  • Drazin RE, Lehrer RI. Fungicidal properties of a chymotrypsin-like cationic protein from human neutrophils: adsorption to Candida parapsilosis. Infect Immun. 1977 Aug;17(2):382–388. [PMC free article] [PubMed]
  • Cech P, Lehrer RI. Heterogeneity of human neutrophil phagolysosomes: functional consequences for candidacidal activity. Blood. 1984 Jul;64(1):147–151. [PubMed]
  • Pollack C, Straley SC, Klempner MS. Probing the phagolysosomal environment of human macrophages with a Ca2+-responsive operon fusion in Yersinia pestis. Nature. 322(6082):834–836. [PubMed]
  • Kamaya T. Lytic action of lysozyme on Candida albicans. Mycopathol Mycol Appl. 1970 Dec 29;42(3):197–207. [PubMed]
  • Marquis G, Montplaisir S, Garzon S, Strykowski H, Auger P. Fungitoxicity of muramidase. Ultrastructural damage to Candida albicans. Lab Invest. 1982 Jun;46(6):627–636. [PubMed]
  • Davies MB. Peptide uptake in Candida albicans. J Gen Microbiol. 1980 Nov;121(1):181–186. [PubMed]
  • Naider F, Becker JM, Katzir-Katchalski E. Utilization of methionine-containing peptides and their derivatives by a methionine-requiring auxotroph of Saccharomyces cerevisiae. J Biol Chem. 1974 Jan 10;249(1):9–20. [PubMed]
  • Scheit KH, Bhargava PM. Effect of seminalplasmin, an antimicrobial protein from bovine semen, on growth and macromolecular synthesis in Candida albicans. Indian J Biochem Biophys. 1985 Feb;22(1):1–7. [PubMed]
  • Cope JE. The porosity of the cell wall of Candida albicans. J Gen Microbiol. 1980 Jul;119(1):253–255. [PubMed]
  • Scherrer R, Louden L, Gerhardt P. Porosity of the yeast cell wall and membrane. J Bacteriol. 1974 May;118(2):534–540. [PMC free article] [PubMed]
  • Habermann E, Jentsch J. Sequenzanalyse des Melittins aus den tryptischen und peptischen Spaltstücken. Hoppe Seylers Z Physiol Chem. 1967 Jan;348(1):37–50. [PubMed]

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