Inhibition of Growth of Candida albicans by Iron-Unsaturated Lactoferrin: Relation to Host-Defense Mechanisms in Chronic Mucocutaneous Candidiasis

Kirkpatrick, Charles H.; Green, Ira; Rich, Robert R.; Schade, Arthur L.

doi:10.1093/infdis/124.6.539

Cited by 181 publications

(99 citation statements)

References 16 publications

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“…Addition of transferrin, lactoferrin or ovotransferrin to culture media has been shown to inhibit growth of C. albicans in vitro (Kirkpatrick et al, 1971 ;Shiraishi & Arai, 1979;Valenti et al, 1986). Such an inhibition was not observed in the present study.…”

Section: Discussioncontrasting

confidence: 72%

Effect of iron deprivation on surface composition and virulence determinants of Candida albicans

Sweet

Douglas

1991

Journal of General Microbiology

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Six strains of Candida albicans were grown in defined medium which had been deferrated by ion-exchange chromatography and then supplemented with FeCl, to give iron concentrations ranging from 0.026 p~ to 0.8 pM. Growth in 0-026 pM-iron (measured as increase in biomass) was reduced by 2659% as compared with that in excess (0.8 p~) iron. With five of the strains, adhesion to buccal epithelial cells was maximal after growth in 0.2-0-4pM-iron, but strain GDH 2023 adhered best when grown in 0 . 0 2 6~~-i r o n .Differences in yeast cell-wall composition were revealed by Zymolyase treatment of whole cells and by 1251-labelling of surface proteins. SDS-PAGE of iodinated proteins, followed by autoradiography, showed quantitative but no qualitative differences in protein profiles of iron-deficient and iron-replete organisms. The ability of all strains to form germ tubes in serum was near-maximal after growth in 0.2-0.4pM-iron but was inhibited by up to 93% following growth in lower concentrations. These results indicate that expression of important virulence attributes by C. albicans is highly dependent on available iron and that expression in vivo may therefore be significantly different from that observed under conventional laboratory conditions.

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Section: Discussioncontrasting

confidence: 72%

Effect of iron deprivation on surface composition and virulence determinants of Candida albicans

Sweet

Douglas

1991

Journal of General Microbiology

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“…We hypothesize that fungistasis by the PMN and perhaps by mucosal LF may increase the likelihood that conidia are physically removed from airways by mucociliary flow before they germinate into hyphae. LF has previously been shown to inhibit the growth of Candida albicans (27). LF has not been reported to act on A. fumigatus, although LF is released by PMN in response to conidia and binding of purified LF to conidia has been mentioned (28).…”

Section: Discussionmentioning

confidence: 99%

Human Polymorphonuclear Leukocytes Inhibit Aspergillus fumigatus Conidial Growth by Lactoferrin-Mediated Iron Depletion

Zarember

Sugui

Chang

et al. 2007

The Journal of Immunology

171

137

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Aspergillus fumigatus, a common mold, rarely infects humans, except during prolonged neutropenia or in cases of chronic granulomatous disease (CGD), a primary immunodeficiency caused by mutations in the NADPH oxidase that normally produces fungicidal reactive oxygen species. Filamentous hyphae of Aspergillus are killed by normal, but not CGD polymorphonuclear leukocytes (PMN); however, the few studies on PMN-mediated host defenses against infectious conidia (spores) of this organism have yielded conflicting results, some showing that PMN do not inhibit conidial growth, with others showing that they do, most likely using reactive oxygen species. Given that CGD patients are exposed daily to hundreds of viable A. fumigatus conidia, yet considerable numbers of them survive years without infection, we reasoned that PMN use ROS-independent mechanisms to combat Aspergillus. We show that human PMN from both normal controls and CGD patients are equipotent at arresting the growth of Aspergillus conidia in vitro, indicating the presence of a reactive oxygen species-independent factor(s). Cell-free supernatants of degranulated normal and CGD neutrophils both suppressed fungal growth and were found to be rich in lactoferrin, an abundant PMN secondary granule protein. Purified iron-poor lactoferrin at concentrations occurring in PMN supernatants (and reported in human mucosal secretions in vivo) decreased fungal growth, whereas saturation of lactoferrin or PMN supernatants with iron, or testing in the presence of excess iron in the form of ferritin, completely abolished activity against conidia. These results demonstrate that PMN lactoferrin sequestration of iron is important for host defense against Aspergillus.

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“…Lactoferrin is an iron-binding substance which inhibits Candida (20) and is probably (58), though not definitely (59) present in specific granules of neutrophils. In our experiments, damage to pseudohyphae was not inhibited by concentrations of iron which were 10-fold higher than that calculated as required to saturate all neutrophil lactoferrin (36,37).…”

Section: Discussionmentioning

confidence: 99%

“…In some circumstances, other mechanisms of candidacidal activity may be involved (18), including granulocyte cationic proteins (19). Other constituents of neutrophil granules, including lactoferrin (20) and lysozyme (21), may also inhibit Candida yeasts. There are morphologic and antigenic (22) differences between Candida yeasts and pseudohyphae and differences in their interactions with neutrophils, so that neutrophil microbicidal mechanisms for yeasts may not be identical to those for pseudohyphae.…”

Section: Introductionmentioning

confidence: 99%

Mechanisms of Attachment of Neutrophils to Candida albicans Pseudohyphae in the Absence of Serum, and of Subsequent Damage to Pseudohyphae by Microbicidal Processes of Neutrophils In Vitro

Daimond¹,

Krzesicki²

1978

J. Clin. Invest.

121

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A B S T R A C T Mechanisms were studied that might explain the attachment and damage to Candida albicans pseudohyphae by neutrophils in the absence of serum. Attachment of neutrophils to pseudo hyphae was inhibited by Candida mannans (1-10 mg/ml), but not by mannose, dextran, chitin, conconavalin A, or highly charged polyamino acids. Contact was also inhibited by pretreatment of Candida before incubation with neutrophils with chymotrypsin, but not trypsin or several inhibitors of proteases. Similar results were obtained with pretreatment of neutrophils, except that trypsin was inhibitory. When pseudohyphae were killed with ultraviolet light, proteinpolysaccharide complexes of mol wt <10,000 were released which appeared to bind to the surfaces of neutrophils and inhibit contact between neutrophils and Candida, as well as other fungi.Damage to Candida by neutrophils was inhibited by agents known to act on neutrophil oxidative microbicidal mechanisms, including sodium cyanide, sodium azide, catalase, superoxide dismutase, and 1, 4 diazobicyclo (2, 2, 2) octane, a singlet oxygen quencher. Neutrophils from a patient with chronic granulomatous disease did not damage Candida at all. However, the hydroxyl radical scavengers mannitol and benzoate were not inhibitory. Cationic proteins and lactoferrin also did not appear to play a major role in this system. Low concentrations of lysozyme which Preliminary findings were presented in part at the Annual

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Inhibition of Growth of Candida albicans by Iron-Unsaturated Lactoferrin: Relation to Host-Defense Mechanisms in Chronic Mucocutaneous Candidiasis

Cited by 181 publications

References 16 publications

Effect of iron deprivation on surface composition and virulence determinants of Candida albicans

Effect of iron deprivation on surface composition and virulence determinants of Candida albicans

Human Polymorphonuclear Leukocytes Inhibit Aspergillus fumigatus Conidial Growth by Lactoferrin-Mediated Iron Depletion

Mechanisms of Attachment of Neutrophils to Candida albicans Pseudohyphae in the Absence of Serum, and of Subsequent Damage to Pseudohyphae by Microbicidal Processes of Neutrophils In Vitro

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