Generation of hydrogen peroxide by Candida albicans and influence on murine polymorphonuclear leukocyte activity

Abstract

Iodide fixation by murine polymorphonuclear leukocytes (PMN) incubated with viable Candida albicans blastoconidia increases directly with yeast cell concentration up to about 3 x 106 cells per ml, but above this concentration bound activity declines dramatically. To understand the basis for this decline, we examined the oxidative metabolism offungi and stimulated PMN and found some remarkable similarities between these cell types. Both produced 14C02 when incubated with [1-14C]glucose, both reduced cytochrome c, and both fixed radiolabeled iodide, although the fungi required exogenous lactoperoxidase. In dose-response experiments, iodination by fungi with lactoperoxidase was identical to that with PMN, i.e., the maximum bound activity occurred in cultures with 106 to 3 x 106 blastoconidia per ml. lodination by fungi with lactoperoxidase was reduced when blastoconidia were incubated at 25°C or in the presence of catalase and the metabolic inhibitors rotenone, antimycin A, and 2-deoxyglucose. Results from assays for oxidation of scopoletin and o-dianisidine showed that 106 blastoconidia in 1.0 ml of medium released 0.5 to 0.7 nmol of I 202 after 1 h, but 3x 106 and 107 cells released significantly less H202. These results suggest that iodide fixation by PMN and low numbers of fungal cells may reflect a cooperative effort, with fungi generating some H202 that reacts with the myeloperoxidase released from the PMN. With high concentrations of blastoconidia, H202 activity appeared to be specifically inhibited, possibly to protect fungal cells from damage. Candida albicans and some related species are part of the normal flora of the upper respiratory, alimentary, and urogenital tracts of most humans. However, in a small percentage of the

Vaginal microbiology of women with acute recurrent vulvovaginal candidiasis

“…These observations suggest that H 2 O 2producing lactobacilli might play a greater role than H 2 O 2negative lactobacilli in inhibiting C. albicans growth in vivo (11). C. albicans both produces and tolerates low concentrations of H 2 O 2 (24); however, in vitro higher concentrations of H 2 O 2 may be candidicidal (6). Paradoxically, in the same study Hillier et al found no evidence of increased colonization or symptomatic candidiasis in pregnant women completely lacking lactobacilli; hence, the importance of H 2 O 2 requires clarification (11).…”

Candida albicanssuppresses nitric oxide (NO) production by interferon-gamma (IFN-γ) and lipopolysaccharide (LPS)-stimulated murine peritoneal macrophages

“…In this regard, Bistoni et al . [ 41, 42] demonstrated that IL‐4 and IL‐10 inhibited NO‐dependent macrophage killing of Candida albicans and that neutralization of IL‐10 by specific antibodies up‐regulated NO production and protected susceptible mice from infection with Candida albicans . These observations suggest that such anti‐inflammatory cytokines, produced by macrophages through stimulation with yeast cells, may be involved in the inhibition of macrophage NO production by Candida albicans .…”

“…For example, Hilger & Danley [ 41] and Danley et al . [ 42] indicated that live Candida albicans suppressed the release of H 2 O 2 by neutrophils, while dead organisms did not. On the other hand, Smail et al .…”

Inhibitory effect of terbinafine on reactive oxygen species (ROS) generation by Candida albicans

“…The mitochondria in C. albicans are capable of generating extracellularly released ROS [5]. In our previous work we demonstrated that ROS generation by C. albicans is dependent on morphogenesis and that their highest levels are found in cells with hyphal form [6].…”