ライフサイエンスコーパス: C. neoformans

1 C. neoformans chemical-genetic responses are largely dis

2 C. neoformans has a defined a-alpha opposite sexual cycl

3 C. neoformans has the capacity to escape phagocytic cell

4 C. neoformans is unique among fungal pathogens in bearin

5 C. neoformans responded to oleic acid supplementation by

6 C. neoformans-induced lysosome damage was observed in in

7 e and shedding were measured in vitro for 48 C. neoformans isolates.

8 A C. neoformans homologue of the Saccharomyces cerevisiae

9 We also engineered a C. neoformans strain that lacks UDP-galactopyranose muta

10 erimental pulmonary infection of mice with a C. neoformans strain that induces protective immunity de

11 In contrast, pulmonary infection with a C. neoformans strain that secretes IFN-gamma, H99gamma,

12 ing less junctional diversity than acapsular C. neoformans-selected cells.

13 es in the environment coincidentally adapted C. neoformans for human virulence.

14 To investigate whether Ab binding affects C. neoformans directly, we analyzed fungal gene expressi

15 avage fluid from WT and SP-D(-/-) mice after C. neoformans infection.

16 pt for the echinocandins were active against C. neoformans, and the triazoles were active against oth

17 l)] displayed high in vitro activity against C. neoformans (IC50 = 0.35 mug/mL, MIC = MFC = 0.63 mug/

18 hat murine pDCs have direct activity against C. neoformans via reactive oxygen species (ROS), a mecha

19 o had decreased fungistatic activity against C. neoformans when activated.

20 K1-S1P pathway promotes host defense against C. neoformans infections by regulating cytokine levels,

21 nse provides a first line of defense against C. neoformans.

22 of new antifungal agents, especially against C. neoformans.

23 d cultured in vitro were fungistatic against C. neoformans, whereas cryptococcal growth was uncontrol

24 l enzymes, and mechanisms of killing against C. neoformans.

25 However, SP-D is not protective against C. neoformans.

26 hage autophagy plays different roles against C. neoformans, depending on the macrophage type and acti

27 itory concentration were synergistic against C. neoformans.

28 the cAMP/PKA and pH-sensing pathways allows C. neoformans to respond to a broad range of host-specif

29 Among C. neoformans-containing myeloid cells, recently recruit

30 The EA was lower for fluconazole and C. neoformans at 86.4%.

31 selected B-1 B cells secreted laminarin- and C. neoformans-binding IgM.

32 ify factors associated with P. marneffei and C. neoformans admissions.

33 alizes with CD44 on the plasma membrane, and C. neoformans cells can adhere to the host cell in areas

34 binding in C. neoformans-infected mice, and C. neoformans-selected B-1 B cells secreted laminarin- a

35 quired for M1 macrophage activation and anti-C. neoformans activity via the production of NO.

36 m by which M1 macrophages mediate their anti-C. neoformans activity remains unknown.

37 ins, CnMVs are distributed inside and around C. neoformans-induced cystic lesions.

38 udies suggested that the interaction between C. neoformans hyaluronic acid and human brain endothelia

39 MARCO facilitates early interactions between C. neoformans and lung-resident cells and promotes the p

40 the importance of the interrelation between C. neoformans and the brain endothelium in establishing

41 lls, which express germline V(H) genes, bind C. neoformans and contribute to early fungal clearance.

42 s CD44 function in the lipid raft, can block C. neoformans adhesion and invasion of HBMEC.

43 ased the frequency of lipid droplets in both C. neoformans and macrophages.

44 lizes Cu as an innate antifungal defense but C. neoformans senses and neutralizes toxic Cu to promote

45 o understand macrophage pathways affected by C. neoformans toxicity.

46 raversal of the blood-brain barrier (BBB) by C. neoformans invitro.

47 ide with rapid fungicidal activity caused by C. neoformans.

48 , our data show that SRA can be exploited by C. neoformans to interfere with the early events of the

49 microscopy to reveal that brain invasion by C. neoformans follows a capillary microembolic event.

50 Infection of macrophages by C. neoformans was associated with alterations in protein

51 beled capsular (24067) and acapsular (Cap67) C. neoformans strains were used to identify C. neoforman

52 ls exhibited the most acapsular and capsular C. neoformans binding in C. neoformans-infected mice, an

53 )12, respectively, in acapsular and capsular C. neoformans-selected B-1a cells.

54 mline V(H) segments were used, with capsular C. neoformans-selected cells having less junctional dive

55 ces of this challenge, we have characterized C. neoformans GMP synthase, the second enzyme in the gua

56 Neutrophils were directly seen to chase C. neoformans cells and then rapidly internalize them.

57 Interestingly, the cystic lesions contained C. neoformans cells embedded within their polysaccharide

58 was found in only a few vacuoles containing C. neoformans previously opsonized with antibody but nev

59 sa1, significantly contributes to serotype D C. neoformans virulence through the induction of laccase

60 udate macrophages in the lungs and decreased C. neoformans-specific Th2 cells in the mediastinal lymp

61 eraction, we utilized a previously described C. neoformans mutant, the gpr4Delta gpr5Delta mutant, wh

62 cryptococci seen in mammalian cells despite C. neoformans being able to grow at bird body temperatur

63 that SIS is conserved between the divergent C. neoformans serotype A and serotype D cryptic sibling

64 MARCO in activation of the CCR2 axis during C. neoformans infection.

65 The protective response induced during C. neoformans strain H99gamma (C. neoformans strain H99

66 and SK1-S1P pathway are interrelated during C. neoformans infections.

67 orylation of FAK, ezrin, and PKCalpha during C. neoformans-HBMEC interaction.

68 lacking SP-D were partially protected during C. neoformans infection; they displayed a longer mean ti

69 was performed using a Caenorhabditis elegans-C. neoformans infection assay.

70 , which we conclude functions as the elusive C. neoformans pheromone-response factor.

71 sly reported the generation of an engineered C. neoformans strain (C. neoformans Deltagcs1) which can

72 CnMVs also enhanced C. neoformans infection of the brain, found in both infe

73 nt negative WASH mutants inefficiently expel C. neoformans.

74 biased lung immunopathology that facilitates C. neoformans growth and dissemination.

75 Sixty-five C. neoformans isolates from clinical trial patients with

76 E] and 2.6% major errors [ME]) and 84.1% for C. neoformans (4.5% VME and 11.4% ME).

77 In this study, occurrence data for C. neoformans and C. gattii were compared by MaxEnt soft

78 The major virulence factor for C. neoformans is a polysaccharide (PS) capsule.

79 of network-assisted predictive genetics for C. neoformans.

80 ere 9.1 h for Candida species and 12.1 h for C. neoformans.

81 ent a genome-scale co-functional network for C. neoformans, CryptoNet, which covers ~81% of the codin

82 Both IgE and IgA were opsonic for C. neoformans and protected against infection in mice.

83 o present the first survey of O-glycans from C. neoformans.

84 n the environment in purine-rich bird guano, C. neoformans experiences a drastic change in nutrient a

85 nduced during C. neoformans strain H99gamma (C. neoformans strain H99 engineered to produce murine IF

86 EC) as the in vitro model to investigate how C. neoformans traverses across the blood-brain barrier.

87 C. neoformans strains were used to identify C. neoformans-binding B cell subsets by flow cytometry.

88 induction of lysosome damage is an important C. neoformans survival strategy and that classical activ

89 show that this protein plays a role also in C. neoformans infection.

90 ual meiotic events has not been attempted in C. neoformans in the style of tetrad analyses performed

91 psular and capsular C. neoformans binding in C. neoformans-infected mice, and C. neoformans-selected

92 e model to explore the importance of CD44 in C. neoformans brain invasion.

93 that mRNA synthesis and decay are coupled in C. neoformans via Rpb4, and this tight coordination prom

94 al transduction proteins and is essential in C. neoformans.

95 ell formation is a novel virulence factor in C. neoformans that promotes establishment of the initial

96 Increased lysosome damage was found in C. neoformans-containing lung cells compared with C. neo

97 the constellation of Cu-responsive genes in C. neoformans and how their expression might contribute

98 have identified a kinase that is involved in C. neoformans internalization by host cells and in host

99 Lastly, we found that MARCO was involved in C. neoformans phagocytosis by resident pulmonary macroph

100 ng confirmed Ipk1 as the major IP5 kinase in C. neoformans: ipk1Delta produced no IP6 or PP-IP5/IP7 a

101 TP, prompting us to investigate ADS lyase in C. neoformans.

102 e, we report that ADE13 encodes ADS lyase in C. neoformans.

103 characterized by generating null mutants in C. neoformans.

104 on would improve immunological parameters in C. neoformans-infected TLR9(-/-) mice.

105 on, and the development of ABPM pathology in C. neoformans-infected lungs.

106 ranscription factor is uniquely regulated in C. neoformans both by the canonical pH-sensing pathway a

107 mechanisms of oxidative stress resistance in C. neoformans.

108 tin may have a potential therapeutic role in C. neoformans infections of the brain.

109 (Cu) acquisition plays an important role in C. neoformans virulence, as mutants that lack Cuf1, whic

110 and macrophage (Mac) polarization status in C. neoformans-infected WT, interleukin-4-deficient (IL-4

111 uptake is a potential therapeutic target in C. neoformans.

112 etworks that control growth and virulence in C. neoformans.

113 Cuf1 target genes required for virulence in C. neoformans.

114 ental induction of lysosome damage increased C. neoformans replication.

115 of lysosome damage correlated with increased C. neoformans replication.

116 In immunocompromised individuals, C. neoformans can lead to life-threatening meningoenceph

117 ibitors with disparate scaffolds can inhibit C. neoformans and suggesting structure-based strategies

118 together, our results show that pDCs inhibit C. neoformans growth in vitro via the production of ROS

119 ely 800 macrophages containing intracellular C. neoformans and identified 163 nonlytic exocytosis eve

120 totoxic effect associated with intracellular C. neoformans residence that manifested itself in impair

121 sponse, and upon phagocytosis, they can kill C. neoformans by evoking an effective immune response th

122 t macrophages display little ability to kill C. neoformans in vitro.

123 nonprotective immunization with heat-killed C. neoformans (HKCn).

124 the oxidative burst inside the macrophages, C. neoformans has developed multilayered redundant molec

125 raft-dependent endocytosis process mediates C. neoformans internalization into HBMEC and that the CD

126 wild type in the insect Galleria mellonella-C. neoformans infection assay.

127 We identified a new C. neoformans Cu transporter, CnCtr1, that is induced by

128 cell division in the presence or absence of C. neoformans infection.

129 er in determining the biological activity of C. neoformans PS.

130 stingly, the metabolic pathway adaptation of C. neoformans to H(2)O(2) treatment was remarkably disti

131 wall changes required for the adaptation of C. neoformans to its host environment.

132 Infection of BALB/c mice with 10(4) CFU of C. neoformans H99 caused a time-dependent induction of I

133 the pathobiological signalling circuitry of C. neoformans and identifies potential anticryptococcal

134 mary outcome of the rate of CSF clearance of C. neoformans over the subsequent 4 weeks was compared.

135 ent of HIV/CM would improve CSF clearance of C. neoformans.

136 lence traits to evaluate the contribution of C. neoformans phenotypic diversity to clinical presentat

137 nd subsequently impaired adaptive control of C. neoformans in the infected lungs.

138 Successful control of C. neoformans infection is dependent on host macrophages

139 hile macrophages are critical for control of C. neoformans, a failure of macrophage response is not t

140 age polarization, limiting innate control of C. neoformans, but ultimately has no effect on cryptococ

141 ear fragmentation and membrane disruption of C. neoformans cells.

142 tics resources for the genetic dissection of C. neoformans phenotypes.

143 ckade effectively abrogated dissemination of C. neoformans to the brain.

144 esults demonstrate a new cytotoxic effect of C. neoformans infection on murine macrophages: fungus-in

145 cells also decreased nonlytic exocytosis of C. neoformans, increased interleukin-6 secretion, and de

146 ation and enhanced macrophage fungistasis of C. neoformans yeasts.

147 ng pathogenic fungi, and the glycobiology of C. neoformans has been a focus of research in the field.

148 Finally we showed the importance of C. neoformans Srx1 in fungal pathogenesis by demonstrati

149 Recently, we reported that ingestion of C. neoformans by mouse macrophages induces early cell cy

150 702 isolates, 13 species) and 44 isolates of C. neoformans against fluconazole.

151 In diploid isolates of C. neoformans var. grubii (serotype AA) and of hybrids w

152 While most isolates of C. neoformans var. grubii belong to one of three major l

153 lular recognition, ingestion, and killing of C. neoformans and discuss the unique and remarkable feat

154 C5a-C5aR signaling in neutrophil killing of C. neoformans in real time.

155 TES and more efficient uptake and killing of C. neoformans These findings suggest that DAP12 acts as

156 some damage and enabled increased killing of C. neoformans.

157 phil migration and its subsequent killing of C. neoformans.

158 augmented understanding of the mechanisms of C. neoformans melanin biosynthesis and cellular assembly

159 ular interactions underlying melanization of C. neoformans have yielded to comprehensive molecular-sc

160 Using a mouse model of C. neoformans infection, we demonstrated that MARCO defi

161 In commonly used mouse models of C. neoformans infections, fungal cells are not contained

162 In this study, we used time-lapse movies of C. neoformans-infected macrophages to delineate the kine

163 e, consistent with the nonspecific nature of C. neoformans virulence known to infect phylogenetically

164 whereby this molecule affects the outcome of C. neoformans infection by inhibiting fungal growth and

165 to shape the role of fungal pathogenesis of C. neoformans.

166 cient method of studying the pathogenesis of C. neoformans.

167 Phagocytosis of C. neoformans promoted cell cycle progression, but infec

168 ts in our lab had shown that phagocytosis of C. neoformans promoted cell cycle progression.

169 and less alveolar macrophage phagocytosis of C. neoformans than did control and B-1a B cell-reconstit

170 , macrophage recruitment and phagocytosis of C. neoformans.

171 Consistent with this, phosphorylation of C. neoformans Hog1 was modulated by both low and high do

172 a unique, genetically diverse population of C. neoformans from sub-Saharan Africa, commonly isolated

173 e mechanism of regulation through the PRE of C. neoformans from all other fungal systems studied to d

174 nce, we determined the transcript profile of C. neoformans in response to elevated Cu or Cu deficienc

175 have elucidated the virulence properties of C. neoformans, less is understood regarding lung host im

176 pulmonary growth and dissemination rates of C. neoformans and extended mice survival.

177 AD1 expression reduces innate recognition of C. neoformans, rendering the yeast resistant to eliminat

178 verning pathogenicity and drug resistance of C. neoformans is imperative.

179 ore infection did not increase resistance of C. neoformans to RIT in vivo.

180 ss the BBB and accumulate at lesion sites of C. neoformans-infected brains.

181 with a highly virulent serotype A strain of C. neoformans (H99).

182 a moderately virulent encapsulated strain of C. neoformans (strain 52D).

183 Studies using a virulent strain of C. neoformans engineered to produce gamma interferon (IF

184 onstrate that a Deltaplb1 knockout strain of C. neoformans has a profound defect in intracellular gro

185 nses against a moderately virulent strain of C. neoformans through effects on leukocyte recruitment,

186 11% of the patients infected with strains of C. neoformans var. grubii with identical genotypes exhib

187 Supplementation of C. neoformans and macrophages with oleic acid significan

188 essential for dissemination and survival of C. neoformans in a host environment was compromised even

189 C. gattii capsules were larger than those of C. neoformans (P < 0.001).

190 ug resistance response upon the treatment of C. neoformans with H(2)O(2).

191 ys important for the growth and virulence of C. neoformans.

192 l growth and exerts a direct lytic effect on C. neoformans extracellular vesicles (EVs).

193 mice infected with either strain H99gamma or C. neoformans strain 52D (unmodified clinical isolate).

194 Dendritic cells (DCs) phagocytose C. neoformans following inhalation.

195 lity to C. neoformans infection by promoting C. neoformans-driven pulmonary IL-5 and eosinophil infil

196 lmonary surfactant protein D (SP-D) protects C. neoformans cells against macrophage-mediated defense

197 stent with the upregulation of Cmt proteins, C. neoformans pulmonary infection results in increased s

198 monstrated that protection against pulmonary C. neoformans infection is associated with the generatio

199 ide a first line of defense during pulmonary C. neoformans infection in mice.

200 We determined that pulmonary C. neoformans infection results in Cu-specific induction

201 eptors on host phagocytes known to recognize C. neoformans Altogether, we have identified a kinase th

202 Purified recombinant C. neoformans ADS lyase shows catalytic activity similar

203 the knockdown of DYRK3 significantly reduces C. neoformans invasion across the HBMEC monolayer in vit

204 lls, DAP12(-/-) NK cells are able to repress C. neoformans growth in vitro Additionally, DAP12(-/-) m

205 to its role in peroxide sensing and response C. neoformans Srx1 was also found to be required for a p

206 vated ATG5-knockout BMMs actually restricted C. neoformans growth more efficiently, suggesting that m

207 strated that the aliphatic moieties of solid C. neoformans melanin ghosts include cell-wall component

208 s the ability of birds to efficiently spread C. neoformans in the environment whilst avoiding systemi

209 ation of an engineered C. neoformans strain (C. neoformans Deltagcs1) which can be contained in lung

210 In summary, C. neoformans harvests lipids from macrophages, and the

211 We show that in the absence of GMP synthase, C. neoformans becomes a guanine auxotroph, the productio

212 Besides serving as an antimicrobial target, C. neoformans ADS lyase inhibitors may also serve as pot

213 solates exhibited a wider range of MICs than C. neoformans.

214 aken together, our findings demonstrate that C. neoformans activates RhoGTPases and subsequently FAK,

215 This is the first demonstration that C. neoformans-derived microvesicles can facilitate crypt

216 In this study, we found that C. neoformans-derived microvesicles (CnMVs) can enhance

217 Thus, our data highlight that C. neoformans, a human-pathogenic basidiomycete, has evo

218 Our results indicate that C. neoformans infection impairs multiple host cellular f

219 These findings indicate that C. neoformans is capable of coopting host SP-D to increa

220 nt several lines of evidence indicating that C. neoformans invasion is mediated through the endocytic

221 It is well known that C. neoformans generally affects immunocompromised hosts;

222 yclophilin A further support the notion that C. neoformans elicits changes in brain endothelial cells

223 Here, we report that C. neoformans infection with highly virulent and less vi

224 In this study, we report that C. neoformans rapidly and transiently repressed ribosoma

225 Our results showed that C. neoformans-infected CD44 KO mice survived longer than

226 These findings suggest that C. neoformans entry takes place on the lipid rafts.

227 The C. neoformans HOG (High Osmolarity Glycerol response) pa

228 The C. neoformans isolates were collected within clinical tr

229 The C. neoformans SRP RNA displays a predicted structure in

230 directly interact with hyaluronic acid, the C. neoformans ligand.

231 ns harvests lipids from macrophages, and the C. neoformans-macrophage interaction is modulated by exo

232 differences in substrate binding between the C. neoformans and human enzymes, with structural insight

233 dentified and functionally characterized the C. neoformans pheromone-response element (PRE).

234 In contrast, the C. neoformans var. neoformans map was completely differe

235 amino acid differences are identified in the C. neoformans crystal structure, in particular a threoni

236 a sex-induced silencing (SIS) pathway in the C. neoformans serotype A var. grubii lineage, in which t

237 exploring the evolution of virulence in the C. neoformans-C. gattii clade.

238 ion maps of the species and varieties of the C. neoformans and C. gattii species complex in Europe an

239 Indeed, additional removal of the C. neoformans H3K9 methyltransferase Clr4 results in los

240 our phenome-based functional analysis of the C. neoformans TF mutant library provides key insights in

241 spite its divergent upstream regulation, the C. neoformans Rim101 protein recognizes a conserved DNA

242 This study revealed that the C. neoformans STE50 gene has both conserved and novel fu

243 s novel activity is conserved throughout the C. neoformans species complex, localized to the Golgi ap

244 This study used the C. neoformans requirement of exogenous obligatory catech

245 Immunoblot analysis using the C. neoformans Tsa1 specific antibody revealed that both

246 -17 axis after intranasal infection with the C. neoformans strain 52D.

247 o the levels found in mice infected with the C. neoformans wild type, and their levels were also depe

248 Deltagcs1 but not in mice infected with the C. neoformans wild type.

249 Thus, C. neoformans produces an autoregulatory peptide that ma

250 and sufficient for neutrophils to attach to C. neoformans but was unable to mediate phagocytosis.

251 Abs tested, the protective IgG1 mAb bound to C. neoformans closest to the cell wall, produced specifi

252 the role of STAT1 in protective immunity to C. neoformans is unknown.

253 n in murine models of protective immunity to C. neoformans.

254 hermore, susceptibility of SP-D(-/-) mice to C. neoformans infection could be restored to the level o

255 IgA reactivity to C. neoformans and A. fumigatus was greater in the BALF o

256 ffei admissions were more common relative to C. neoformans admissions during months of high (>/=85%)

257 investigate the role of IgM in resistance to C. neoformans, we compared the survival, fungal burden,

258 play a role in the early immune response to C. neoformans but is not required for classical macropha

259 a brake on the pulmonary immune response to C. neoformans by promoting pulmonary eosinophilia and by

260 ined the role of SK1 in the host response to C. neoformans infection.

261 nt inhibitory role in the immune response to C. neoformans Infectious outcomes in DAP12(-/-) mice, in

262 we examined the role of SP-D in response to C. neoformans using SP-D(-)/(-) mice.

263 role played by SP-D during host responses to C. neoformans and consequently imparts insight into pote

264 ies demonstrate that protective responses to C. neoformans challenge in immunized mice include classi

265 othesized that SP-D alters susceptibility to C. neoformans by dysregulating the innate pulmonary immu

266 lusion that SP-D increases susceptibility to C. neoformans infection by promoting C. neoformans-drive

267 ce manifested no increased susceptibility to C. neoformans, as measured by survival, but had fewer al

268 ary eosinophilia and are more susceptible to C. neoformans infection than WT mice.

269 t affect the migration of neutrophils toward C. neoformans but almost completely abolished phagocytos

270 Few antifungals can treat C. neoformans infections, and drug resistance is increas

271 during the protective response to wild-type C. neoformans in mice previously immunized with H99gamma

272 y protected against challenge with wild-type C. neoformans.

273 Upon C. neoformans engagement, GM1 is internalized through ve

274 present a multidisciplinary study validating C. neoformans FTase (CnFTase) as a drug target, showing

275 odel of inhalational infection with virulent C. neoformans H99, we demonstrate a role for IL-33-depen

276 e mastermind-like within mature T cells with C. neoformans Inhibition of T cell-restricted Notch sign

277 uman brain endothelial cells challenged with C. neoformans was resolved using a label-free differenti

278 Compared with C. neoformans MICs, C. gattii MICs were lower for flucyt

279 oformans-containing lung cells compared with C. neoformans-free cells.

280 ar. grubii (serotype AA) and of hybrids with C. neoformans var. neoformans (serotype AD) such aneuplo

281 Incubation with C. neoformans resulted in enhanced activation of Erk and

282 eolar lavage fluid of all mice infected with C. neoformans Deltagcs1 but not in mice infected with th

283 r alpha were found in the mice infected with C. neoformans Deltagcs1 in comparison to the levels foun

284 2-deficient (T1/ST2(-/-)) mice infected with C. neoformans H99 had improved survival with a decreased

285 ating that SP-D-deficient mice infected with C. neoformans have a lower fungal burden and live longer

286 f eosinophils and/or IL-5 were infected with C. neoformans to assess the role of these innate immune

287 pidly than wild-type mice when infected with C. neoformans, and Anxa2(-/-) mice exhibited enhanced in

288 ivation in mice experimentally infected with C. neoformans.

289 ferent times after intranasal infection with C. neoformans (24067).

290 B cell response to pulmonary infection with C. neoformans and reveal that IgM-producing B-1a cells,

291 M in resistance to intranasal infection with C. neoformans in mice and suggest that the mechanism by

292 rent studies demonstrate that infection with C. neoformans strain H99gamma in mice with macrophage-sp

293 ven an experimental pulmonary infection with C. neoformans strain H99gamma.

294 mpared to wild-type mice upon infection with C. neoformans This increase in survival correlated with

295 photericin B against systemic infection with C. neoformans.

296 ling events in HBMEC during interaction with C. neoformans.

297 led analysis of macrophage interactions with C. neoformans during infection.

298 -/-) mice were infected intratracheally with C. neoformans.

299 the dynamic interactions of neutrophils with C. neoformans and the underlying mechanisms in real time

300 the dynamic interactions of neutrophils with C. neoformans, demonstrating a crucial role of C5a-C5aR