Abstract
Cryptococcus gattii is an environmental yeast-like fungus capable of
causing disease in a wide range of animal hosts. In humans, disease
progression begins after inhalation of the infectious propagule leading
to infection of the lung. The infective yeast cells can then disseminate
to the central nervous system, resulting in meningoencephalitis, which
can be fatal if left untreated.
Closely related strains of C. gattii exhibit significantly different
degrees of virulence in the mammalian host. As fungi utilize absorbtive
nutrition producing a range of secreted degrative enzymes, and as
these may invoke a host response, the fungal secretome is likely to be
very important in modulating host-pathogen interactions.
We compared the secretomes of two C. gattii strains, one categorized
as hypervirulent and the other exhibiting low-level virulence. C. gattii
was grown under conditions designed to be as similar as possible to
those encountered in vivo. Secreted proteins were captured from the
culture supernatant and concentrated protein was analysed via 1D
nanoLC-MS/MS.
The two strains exhibited significantly different secreted proteins. A
total of 27 proteins were identified with only four protein identifications
being shared by both strains. The secretome of the hypervirulent strain,
R265, primarily included uncharacterized proteins. However, bioinformatic
analysis suggested these proteins contained catalytic regions with
roles in carbohydrate degradation. The less virulent R272 strain secreted
a more diverse set of proteins including enolase and transaldolase,
enzymes which are canonically involved in glycolysis and the pentose
phosphate pathway respectively. Interestingly however, these proteins
are also both described fungal allergens that bind IgE.
This study has found that closely related strains of C. gattii
exhibiting different levels of virulence secrete very different cohorts of
proteins. The proportionally greater number of proteins with a putative
role in nutrient scavenging in the hypervirulent strain could suggest
this strain has a greater capacity to source nutrients from a range of
available substrates and hence more readily expand in new ecological
niches. The greater number of potentially allergenic proteins in the
strain exhibiting low-level virulence could indicate this strain triggers a
more effective immune response in the mammalian host leading to
clearance of the pathogen.
causing disease in a wide range of animal hosts. In humans, disease
progression begins after inhalation of the infectious propagule leading
to infection of the lung. The infective yeast cells can then disseminate
to the central nervous system, resulting in meningoencephalitis, which
can be fatal if left untreated.
Closely related strains of C. gattii exhibit significantly different
degrees of virulence in the mammalian host. As fungi utilize absorbtive
nutrition producing a range of secreted degrative enzymes, and as
these may invoke a host response, the fungal secretome is likely to be
very important in modulating host-pathogen interactions.
We compared the secretomes of two C. gattii strains, one categorized
as hypervirulent and the other exhibiting low-level virulence. C. gattii
was grown under conditions designed to be as similar as possible to
those encountered in vivo. Secreted proteins were captured from the
culture supernatant and concentrated protein was analysed via 1D
nanoLC-MS/MS.
The two strains exhibited significantly different secreted proteins. A
total of 27 proteins were identified with only four protein identifications
being shared by both strains. The secretome of the hypervirulent strain,
R265, primarily included uncharacterized proteins. However, bioinformatic
analysis suggested these proteins contained catalytic regions with
roles in carbohydrate degradation. The less virulent R272 strain secreted
a more diverse set of proteins including enolase and transaldolase,
enzymes which are canonically involved in glycolysis and the pentose
phosphate pathway respectively. Interestingly however, these proteins
are also both described fungal allergens that bind IgE.
This study has found that closely related strains of C. gattii
exhibiting different levels of virulence secrete very different cohorts of
proteins. The proportionally greater number of proteins with a putative
role in nutrient scavenging in the hypervirulent strain could suggest
this strain has a greater capacity to source nutrients from a range of
available substrates and hence more readily expand in new ecological
niches. The greater number of potentially allergenic proteins in the
strain exhibiting low-level virulence could indicate this strain triggers a
more effective immune response in the mammalian host leading to
clearance of the pathogen.
| Original language | English |
|---|---|
| Article number | P222 |
| Pages (from-to) | 163-163 |
| Number of pages | 1 |
| Journal | Mycoses |
| Volume | 55 |
| Issue number | S4 |
| Publication status | Published - Jun 2012 |
| Event | 18th Congress of the International Society for Human and Animal Mycology - Berlin, Germany Duration: 11 Jun 2012 → 15 Jun 2012 |