Disseminated fungal infections caused by Candida species are associated with homing of the pathogen to specific organs in human and murine hosts. Kidneys are a primary target organ of Candida albicans, and invasion into the kidney medulla can lead to loss of renal function and death. Therefore, development of noninvasive methods to assess kidney infections could aid in the management of disseminated candidemia. We describe a magnetic resonance imaging method utilizing iron oxide-based contrast agents to noninvasively assess recruitment of phagocytes and kidney inflammation. C. albicans also colonizes the brain and can cause meningoencephalitis. We describe additional imaging methods to assess loss of the blood-brain barrier function that initiates brain infections.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Investigator-Initiated Intramural Research Projects (ZIA)
Project #
1ZIASC009173-28
Application #
9344110
Study Section
Project Start
Project End
Budget Start
Budget End
Support Year
28
Fiscal Year
2016
Total Cost
Indirect Cost
Name
Clinical Sciences
Department
Type
DUNS #
City
State
Country
Zip Code
Navarathna, Dhammika H M L P; Pathirana, Ruvini U; Lionakis, Michail S et al. (2016) Candida albicans ISW2 Regulates Chlamydospore Suspensor Cell Formation and Virulence In Vivo in a Mouse Model of Disseminated Candidiasis. PLoS One 11:e0164449
Navarathna, Dhammika H; Roberts, David D; Munasinghe, Jeeva et al. (2016) Imaging Candida Infections in the Host. Methods Mol Biol 1356:69-78
Navarathna, Dhammika H M L P; Stein, Erica V; Lessey-Morillon, Elizabeth C et al. (2015) CD47 Promotes Protective Innate and Adaptive Immunity in a Mouse Model of Disseminated Candidiasis. PLoS One 10:e0128220
Pendrak, Michael L; Roberts, David D (2015) Hbr1 Activates and Represses Hyphal Growth in Candida albicans and Regulates Fungal Morphogenesis under Embedded Conditions. PLoS One 10:e0126919
Navarathna, Dhammika H M L P; Munasinghe, Jeeva; Lizak, Martin J et al. (2013) MRI confirms loss of blood-brain barrier integrity in a mouse model of disseminated candidiasis. NMR Biomed 26:1125-34
Martin-Manso, Gema; Navarathna, Dhammika H M L P; Galli, Susana et al. (2012) Endogenous thrombospondin-1 regulates leukocyte recruitment and activation and accelerates death from systemic candidiasis. PLoS One 7:e48775
Navarathna, Dhammika H M L P; Lionakis, Michail S; Lizak, Martin J et al. (2012) Urea amidolyase (DUR1,2) contributes to virulence and kidney pathogenesis of Candida albicans. PLoS One 7:e48475
Peterson, Alexander W; Pendrak, Michael L; Roberts, David D (2011) ATP binding to hemoglobin response gene 1 protein is necessary for regulation of the mating type locus in Candida albicans. J Biol Chem 286:13914-24
Navarathna, Dhammika H M L P; Das, Aditi; Morschhauser, Joachim et al. (2011) Dur3 is the major urea transporter in Candida albicans and is co-regulated with the urea amidolyase Dur1,2. Microbiology 157:270-9
Pendrak, Michael L; Roberts, David D (2011) Ribosomal RNA processing in Candida albicans. RNA 17:2235-48

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