Deprecated: Implicit conversion from float 231.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534
Deprecated: Implicit conversion from float 231.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534
Deprecated: Implicit conversion from float 231.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534
Deprecated: Implicit conversion from float 231.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534
Deprecated: Implicit conversion from float 231.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534
Deprecated: Implicit conversion from float 231.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534
Deprecated: Implicit conversion from float 231.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534
Warning: imagejpeg(C:\Inetpub\vhosts\kidney.de\httpdocs\phplern\29775474
.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
): e1006978
Nephropedia Template TP
gab.com Text
Twit Text FOAVip
Twit Text #
English Wikipedia
The Cryptococcus neoformans Titan cell is an inducible and regulated morphotype
underlying pathogenesis
#MMPMID29775474
Dambuza IM
; Drake T
; Chapuis A
; Zhou X
; Correia J
; Taylor-Smith L
; LeGrave N
; Rasmussen T
; Fisher MC
; Bicanic T
; Harrison TS
; Jaspars M
; May RC
; Brown GD
; Yuecel R
; MacCallum DM
; Ballou ER
PLoS Pathog
2018[May]; 14
(5
): e1006978
PMID29775474
show ga
Fungal cells change shape in response to environmental stimuli, and these
morphogenic transitions drive pathogenesis and niche adaptation. For example,
dimorphic fungi switch between yeast and hyphae in response to changing
temperature. The basidiomycete Cryptococcus neoformans undergoes an unusual
morphogenetic transition in the host lung from haploid yeast to large, highly
polyploid cells termed Titan cells. Titan cells influence fungal interaction with
host cells, including through increased drug resistance, altered cell size, and
altered Pathogen Associated Molecular Pattern exposure. Despite the important
role these cells play in pathogenesis, understanding the environmental stimuli
that drive the morphological transition, and the molecular mechanisms underlying
their unique biology, has been hampered by the lack of a reproducible in vitro
induction system. Here we demonstrate reproducible in vitro Titan cell induction
in response to environmental stimuli consistent with the host lung. In vitro
Titan cells exhibit all the properties of in vivo generated Titan cells, the
current gold standard, including altered capsule, cell wall, size, high mother
cell ploidy, and aneuploid progeny. We identify the bacterial peptidoglycan
subunit Muramyl Dipeptide as a serum compound associated with shift in cell size
and ploidy, and demonstrate the capacity of bronchial lavage fluid and bacterial
co-culture to induce Titanisation. Additionally, we demonstrate the capacity of
our assay to identify established (cAMP/PKA) and previously undescribed (USV101)
regulators of Titanisation in vitro. Finally, we investigate the Titanisation
capacity of clinical isolates and their impact on disease outcome. Together,
these findings provide new insight into the environmental stimuli and molecular
mechanisms underlying the yeast-to-Titan transition and establish an essential in
vitro model for the future characterization of this important morphotype.