Two different NO-dependent mechanisms account for the low virulence of a non-mycelial morphological mutant of Candida albicans.
We have previously described the low virulence of a Candida albicans morphological mutant: 92'. We have now used this strain to examine the role of phagocytes in its pathogenesis. Our results show that C. albicans 92' cannot evade innate host macrophage defence mechanisms as efficiently as the parental strain. In addition to the high susceptibility to phagocytosis by peritoneal macrophages, the NO produced by macrophages is a very important element in the low virulence of this agerminative mutant, a thesis supported by in vivo and in vitro experiments. Whereas the parental strain was able to inhibit macrophage NO production, the mutant was quite inefficient at reducing NO production by macrophages. In addition, the mutant showed high sensitivity to a NO generator. Treatment of mice with aminoguanidine (a preferred inducible NO synthase inhibitor) caused 90% mortality in 92' systemic infection, thus supporting a role for NO in the low virulence of this strain. Our data show that both the low inhibitory effect of 92' on macrophage NO production and the higher sensitivity to NO underlie the low virulence of this strain.
Diez-Orejas
R
R
Departamento de Microbiología II, Facultad de Farmacia, Universidad Complutense, Madrid, Spain. gloros@eucmax.sim.ucm.es
Molero
G
G
Moro
M A
MA
Gil
C
C
Nombela
C
C
Sánchez-Pérez
M
M
D000818:Animals; D002176:Candida albicans / Q000187:drug effects / Q000235:genetics / Q000472:pathogenicity*; D002177:Candidiasis / Q000503:physiopathology; D006146:Guanidines / Q000008:administration & dosage / Q000009:adverse effects; D017737:Macrophages, Peritoneal / Q000166:cytology / Q000276:immunology / Q000382:microbiology; D051379:Mice; D008807:Mice, Inbred BALB C; D008981:Molsidomine / Q000031:analogs & derivatives / Q000494:pharmacology; D016296:Mutagenesis; D009566:Nitrates; D009569:Nitric Oxide / Q000096:biosynthesis / Q000378:metabolism*; D020030:Nitric Oxide Donors / Q000494:pharmacology; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors / Q000378:metabolism; D052247:Nitric Oxide Synthase Type II; D009573:Nitrites / Q000378:metabolism; D014774:Virulence
D006146:Guanidines; D009566:Nitrates; D020030:Nitric Oxide Donors; D009573:Nitrites; C039642:peroxynitric acid; D009569:Nitric Oxide; C002385:linsidomine; D008981:Molsidomine; D019001:Nitric Oxide Synthase; D052247:Nitric Oxide Synthase Type II; C496317:Nos2 protein, mouse; C004479:pimagedine