Journal article
Candida albicans Filamentation Does Not Require the cAMP-PKA Pathway In Vivo
mBio, Vol.13(3), pp.e0085122-e0085122
04/27/2022
DOI: 10.1128/mbio.00851-22
PMCID: PMC9239198
PMID: 35475642
Abstract
The fungus
Candida albicans
causes a wide range of disease in humans from common diaper rash to life-threatening infections in patients with compromised immune systems. As such, the mechanisms for its ability to cause disease are of wide interest.
ABSTRACT
Candida albicans
is one of the most prevalent human fungal pathogens. Its ability to transition between budding yeast and filamentous morphological forms (pseudohyphae and hyphae) is tightly associated with its pathogenesis. Based on
in vitro
studies, the cAMP-protein kinase A (PKA) pathway is a key regulator of
C. albicans
morphogenesis. Using an intravital imaging approach, we investigated the role of the cAMP-PKA pathway during infection. Consistent with their roles
in vitro
, the downstream effectors of the cAMP-PKA pathway Efg1 and Nrg1 function, respectively, as an activator and a repressor of
in vivo
filamentation. Surprisingly, strains lacking the adenylyl cyclase,
CYR1
, showed only slightly reduced filamentation
in vivo
despite being completely unable to filament in RPMI + 10% serum at 37°C. Consistent with these findings, deletion of the catalytic subunits of PKA (Tpk1 and Tpk2), either singly or in combination, generated strains that also filamented
in vivo
but not
in vitro
.
In vivo
transcription profiling of
C. albicans
isolated from both ear and kidney tissue showed that the expression of a set of 184 environmentally responsive genes correlated well with
in vitro
filamentation (
R
2
, 0.62 to 0.68) genes. This concordance suggests that the
in vivo
and
in vitro
transcriptional responses are similar but that the upstream regulatory mechanisms are distinct. As such, these data emphatically emphasize that
C. albicans
filamentation is a complex phenotype that occurs in different environments through an intricate network of distinct regulatory mechanisms.
IMPORTANCE
The fungus
Candida albicans
causes a wide range of disease in humans from common diaper rash to life-threatening infections in patients with compromised immune systems. As such, the mechanisms for its ability to cause disease are of wide interest. An intensely studied virulence property of
C. albicans
is its ability to switch from a round yeast form to filament-like forms (hyphae and pseudohyphae). Surprisingly, we have found that a key signaling pathway that regulates this transition
in vitro
, the protein kinase A pathway, is not required for filamentation during infection of the host. Our work not only demonstrates that the regulation of filamentation depends upon the specific environment
C. albicans
inhabits but also underscores the importance of studying these mechanisms during infection.
Details
- Title: Subtitle
- Candida albicans Filamentation Does Not Require the cAMP-PKA Pathway In Vivo
- Creators
- Rohan S. Wakade - University of IowaJuraj Kramara - University of IowaMelanie Wellington - University of IowaDamian J. Krysan - Roy J. and Lucille A. Carver College of Medicine
- Contributors
- Judith Berman (Editor)
- Resource Type
- Journal article
- Publication Details
- mBio, Vol.13(3), pp.e0085122-e0085122
- DOI
- 10.1128/mbio.00851-22
- PMID
- 35475642
- PMCID
- PMC9239198
- NLM abbreviation
- mBio
- ISSN
- 2150-7511
- eISSN
- 2150-7511
- Grant note
- DOI: 10.13039/100000060, name: HHS | NIH | National Institute of Allergy and Infectious Diseases, award: 5R01AI133409; DOI: 10.13039/100000060, name: HHS | NIH | National Institute of Allergy and Infectious Diseases, award: 5R21AI157341
- Language
- English
- Date published
- 04/27/2022
- Academic Unit
- Microbiology and Immunology; Stead Family Department of Pediatrics; Infectious Disease (Pediatrics)
- Record Identifier
- 9984297430702771
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