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.jpg): Failed to open stream: No such file or directory in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 117 PLoS+Pathog
2018 ; 14
(5
): e1006982
Nephropedia Template TP
gab.com Text
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English Wikipedia
Titan cells formation in Cryptococcus neoformans is finely tuned by environmental
conditions and modulated by positive and negative genetic regulators
#MMPMID29775480
Hommel B
; Mukaremera L
; Cordero RJB
; Coelho C
; Desjardins CA
; Sturny-Leclère A
; Janbon G
; Perfect JR
; Fraser JA
; Casadevall A
; Cuomo CA
; Dromer F
; Nielsen K
; Alanio A
PLoS Pathog
2018[May]; 14
(5
): e1006982
PMID29775480
show ga
The pathogenic fungus Cryptococcus neoformans exhibits morphological changes in
cell size during lung infection, producing both typical size 5 to 7 ?m cells and
large titan cells (> 10 ?m and up to 100 ?m). We found and optimized in vitro
conditions that produce titan cells in order to identify the ancestry of titan
cells, the environmental determinants, and the key gene regulators of titan cell
formation. Titan cells generated in vitro harbor the main characteristics of
titan cells produced in vivo including their large cell size (>10 ?m), polyploidy
with a single nucleus, large vacuole, dense capsule, and thick cell wall. Here we
show titan cells derived from the enlargement of progenitor cells in the
population independent of yeast growth rate. Change in the incubation medium,
hypoxia, nutrient starvation and low pH were the main factors that trigger titan
cell formation, while quorum sensing factors like the initial inoculum
concentration, pantothenic acid, and the quorum sensing peptide Qsp1p also
impacted titan cell formation. Inhibition of ergosterol, protein and nucleic acid
biosynthesis altered titan cell formation, as did serum, phospholipids and
anti-capsular antibodies in our settings. We explored genetic factors important
for titan cell formation using three approaches. Using H99-derivative strains
with natural genetic differences, we showed that titan cell formation was
dependent on LMP1 and SGF29 genes. By screening a gene deletion collection, we
also confirmed that GPR4/5-RIM101, and CAC1 genes were required to generate titan
cells and that the PKR1, TSP2, USV101 genes negatively regulated titan cell
formation. Furthermore, analysis of spontaneous Pkr1 loss-of-function clinical
isolates confirmed the important role of the Pkr1 protein as a negative regulator
of titan cell formation. Through development of a standardized and robust in
vitro assay, our results provide new insights into titan cell biogenesis with the
identification of multiple important factors/pathways.