Loss of Opi3 causes a lipid imbalance that influences the virulence traits of Cryptococcus neoformans but not cryptococcosis
The basidiomycete fungus is a useful model for investigating mechanisms of fungal pathogenesis in mammalian hosts. This pathogen is the causative agent of cryptococcal meningitis in immunocompromised patients and is in the critical priority group of the World Health Organization fungal priority path...
Saved in:
Published in | Frontiers in cellular and infection microbiology Vol. 14; p. 1448229 |
---|---|
Main Authors | , , , , , , |
Format | Journal Article |
Language | English |
Published |
Switzerland
Frontiers Media S.A
13.08.2024
|
Subjects | |
Online Access | Get full text |
Cover
Loading…
Summary: | The basidiomycete fungus
is a useful model for investigating mechanisms of fungal pathogenesis in mammalian hosts. This pathogen is the causative agent of cryptococcal meningitis in immunocompromised patients and is in the critical priority group of the World Health Organization fungal priority pathogens list. In this study, we employed a mutant lacking the
gene encoding a methylene-fatty-acyl-phospholipid synthase to characterize the role of phosphatidylcholine (PC) and lipid homeostasis in the virulence of
. We first confirmed that
was required for growth in nutrient limiting conditions, a phenotype that could be rescued with exogenous choline and PC. Additionally, we established that loss of Opi3 and the lack of PC lead to an accumulation of neutral lipids in lipid droplets and alterations in major lipid classes. The growth defect of the
mutant was also rescued by sorbitol and polyethylene glycol (PEG), a result consistent with protection of ER function from the stress caused by lipid imbalance. We then examined the impact of Opi3 on virulence and found that the dependence of PC synthesis on Opi3 caused reduced capsule size and this was accompanied by an increase in shed capsule polysaccharide and changes in cell wall composition. Further tests of virulence demonstrated that survival in alveolar macrophages and the ability to cause disease in mice were not impacted by loss of Opi3 despite the choline auxotrophy of the mutant
. Overall, this work establishes the contribution of lipid balance to virulence factor elaboration by
and suggests that host choline is sufficient to support proliferation during disease. |
---|---|
Bibliography: | ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23 Edited by: Yong-Sun Bahn, Yonsei University, Republic of Korea Alex Andrianopoulos, The University of Melbourne, Australia Present address: Linda Horianopoulos, Wisconsin Energy Institute, University of Wisconsin–Madison, Madison, WI, United States Reviewed by: Chaoyang Xue, Rutgers University, Newark, United States Felipe H. Santiago-Tirado, University of Notre Dame, United States |
ISSN: | 2235-2988 2235-2988 |
DOI: | 10.3389/fcimb.2024.1448229 |