Abstract
Cryptococcus neoformans is a facultative intracellular pathogen. The most distinctive feature of C. neoformans is a polysaccharide capsule that enlarges depending on environmental stimuli. The mechanism by which C. neoformans avoids killing during phagocytosis is unknown. We hypothesized that capsule growth conferred resistance to microbicidal molecules produced by the host during infection, particularly during phagocytosis. We observed that capsule enlargement conferred resistance to reactive oxygen species produced by H2O2 that was not associated with a higher catalase activity, suggesting a new function for the capsule as a scavenger of reactive oxidative intermediates. Soluble capsular polysaccharide protected C.neoformans and Saccharomyces cerevisiae from killing by H2O2. Acapsular mutants had higher susceptibility to free radicals. Capsular polysaccharide acted as an antioxidant in the nitroblue tetrazolium (NBT) reduction coupled to β-nicotinamide adenine dinucleotide (NADH)/phenazine methosulfate (PMS) assay. Capsule enlargement conferred resistance to antimicrobial peptides and the antifungal drug Amphotericin B. Interestingly, the capsule had no effect on susceptibility to azoles and increased susceptibility to fluconazole. Capsule enlargement reduced phagocytosis by environmental predators, although we also noticed that in this system, starvation of C.neoformans cells produced resistance to phagocytosis. Our results suggest that capsular enlargement is a mechanism that enhances C. neoformans survival when ingested by phagocytic cells.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 2043-2057 |
| Number of pages | 15 |
| Journal | Cellular Microbiology |
| Volume | 10 |
| Issue number | 10 |
| DOIs | |
| State | Published - 2008 |
| Externally published | Yes |
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ASJC Scopus subject areas
- Clinical Biochemistry
- Microbiology
Cite this
Capsule enlargement in Cryptococcus neoformans confers resistance to oxidative stress suggesting a mechanism for intracellular survival. / Zaragoza, Oscar; Chrisman, Cara J.; Castelli, Maria Victoria; Frases, Susana; Cuenca-Estrella, Manuel; Rodríguez-Tudela, Juan Luis; Casadevall, Arturo.
In: Cellular Microbiology, Vol. 10, No. 10, 2008, p. 2043-2057.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Capsule enlargement in Cryptococcus neoformans confers resistance to oxidative stress suggesting a mechanism for intracellular survival
AU - Zaragoza, Oscar
AU - Chrisman, Cara J.
AU - Castelli, Maria Victoria
AU - Frases, Susana
AU - Cuenca-Estrella, Manuel
AU - Rodríguez-Tudela, Juan Luis
AU - Casadevall, Arturo
PY - 2008
Y1 - 2008
N2 - Cryptococcus neoformans is a facultative intracellular pathogen. The most distinctive feature of C. neoformans is a polysaccharide capsule that enlarges depending on environmental stimuli. The mechanism by which C. neoformans avoids killing during phagocytosis is unknown. We hypothesized that capsule growth conferred resistance to microbicidal molecules produced by the host during infection, particularly during phagocytosis. We observed that capsule enlargement conferred resistance to reactive oxygen species produced by H2O2 that was not associated with a higher catalase activity, suggesting a new function for the capsule as a scavenger of reactive oxidative intermediates. Soluble capsular polysaccharide protected C.neoformans and Saccharomyces cerevisiae from killing by H2O2. Acapsular mutants had higher susceptibility to free radicals. Capsular polysaccharide acted as an antioxidant in the nitroblue tetrazolium (NBT) reduction coupled to β-nicotinamide adenine dinucleotide (NADH)/phenazine methosulfate (PMS) assay. Capsule enlargement conferred resistance to antimicrobial peptides and the antifungal drug Amphotericin B. Interestingly, the capsule had no effect on susceptibility to azoles and increased susceptibility to fluconazole. Capsule enlargement reduced phagocytosis by environmental predators, although we also noticed that in this system, starvation of C.neoformans cells produced resistance to phagocytosis. Our results suggest that capsular enlargement is a mechanism that enhances C. neoformans survival when ingested by phagocytic cells.
AB - Cryptococcus neoformans is a facultative intracellular pathogen. The most distinctive feature of C. neoformans is a polysaccharide capsule that enlarges depending on environmental stimuli. The mechanism by which C. neoformans avoids killing during phagocytosis is unknown. We hypothesized that capsule growth conferred resistance to microbicidal molecules produced by the host during infection, particularly during phagocytosis. We observed that capsule enlargement conferred resistance to reactive oxygen species produced by H2O2 that was not associated with a higher catalase activity, suggesting a new function for the capsule as a scavenger of reactive oxidative intermediates. Soluble capsular polysaccharide protected C.neoformans and Saccharomyces cerevisiae from killing by H2O2. Acapsular mutants had higher susceptibility to free radicals. Capsular polysaccharide acted as an antioxidant in the nitroblue tetrazolium (NBT) reduction coupled to β-nicotinamide adenine dinucleotide (NADH)/phenazine methosulfate (PMS) assay. Capsule enlargement conferred resistance to antimicrobial peptides and the antifungal drug Amphotericin B. Interestingly, the capsule had no effect on susceptibility to azoles and increased susceptibility to fluconazole. Capsule enlargement reduced phagocytosis by environmental predators, although we also noticed that in this system, starvation of C.neoformans cells produced resistance to phagocytosis. Our results suggest that capsular enlargement is a mechanism that enhances C. neoformans survival when ingested by phagocytic cells.
UR - http://www.scopus.com/inward/record.url?scp=51549103890&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=51549103890&partnerID=8YFLogxK
U2 - 10.1111/j.1462-5822.2008.01186.x
DO - 10.1111/j.1462-5822.2008.01186.x
M3 - Article
C2 - 18554313
AN - SCOPUS:51549103890
VL - 10
SP - 2043
EP - 2057
JO - Cellular Microbiology
JF - Cellular Microbiology
SN - 1462-5814
IS - 10
ER -