Abstract
Candida albicans, a species of fungi, can thrive in diverse niches of its mammalian hosts; it is a normal resident of the GI tract and mucosal surfaces but it can also enter the bloodstream and colonize internal organs causing serious disease. The ability of C. albicans to thrive in these different host environments has been attributed, at least in part, to its ability to assume different morphological forms. In this work, we examine one such morphological change known as white-opaque switching. White cells are the default state of C. albicans, and most animal studies have been carried out exclusively with white cells. Here, we compared the proliferation of white and opaque cells in two murine models of infection and also monitored, using specially constructed strains, switching between the two states in the host. We found that white cells outcompeted opaque cells in many niches; however, we show for the first time that in some organs (specifically, the heart and spleen), opaque cells competed favorably with white cells and, when injected on their own, could colonize these organs. In environments where the introduced white cells outcompeted the introduced opaque cells, we observed high rates of opaque-to-white switching. We did not observe white-to-opaque switching in any of the niches we examined.
Highlights
Candida albicans is a source of serious fungal infections in the United States; it is the fourth most commonly cultured microbe from blood [1]
This approach offers several advantages when compared with previous studies: 1) it does not require the use of auxotrophies or drug resistance markers that have been shown to affect C. albicans behavior in vivo [34,35], 2) it does not require the use of strains that are artificially “locked” in one cell-type or another, for example by deleting or overexpressing the master regulator Wor1 [29,36,37], and 3) it does not require any downstream processing, such as qPCR, which can introduce errors through amplification
White and opaque cells are distinct, heritable cell types of C. albicans produced from the same genome
Summary
Candida albicans is a source of serious fungal infections in the United States; it is the fourth most commonly cultured microbe from blood [1]. Unlike other major fungal pathogens, C. albicans is a part of the normal human microbiome, in the gastrointestinal tract, skin, oral cavity, and other mucosal surfaces [2]. C. albicans poses health risks, for people whose immune system is suppressed, who have surgeries, implanted medical devices, or who have been treated with long courses of antibiotics. The attributable mortality from C. albicans bloodstream infections in adults is at least 15% and has been reported to be as high as 40% [3].
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