Murine Models of Candida Gastrointestinal Colonization and Dissemination

Koh, Andrew Y.

doi:10.1128/ec.00196-13

Cited by 107 publications

(112 citation statements)

References 99 publications

(96 reference statements)

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“…Mice do not naturally harbor Candida species and require some repression of the natural microbiome to sustain Candida colonization (Koh 2013), while the "natural" gut mycobiome of laboratory mice is strongly influenced by the environment (food source, bedding etc. ; Hallen-Adams pers obs).…”

Section: Discussionmentioning

confidence: 99%

The human gut mycobiome: pitfalls and potentials--a mycologists perspective

2015

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Abstract:We have entered the Age of the Microbiome, with new studies appearing constantly and whole journals devoted to the human microbiome. While bacteria outnumber other gut microbes by orders of magnitude, eukaryotes are consistently found in the human gut and are represented primarily by the fungi. Compiling 36 studies 1917-2015 we found at least 267 distinct fungal taxa have been reported from the human gut, and seemingly every new study includes one or more fungi not previously described from this niche. This diversity, while impressive, is illusory. If we examine gut fungi, we will quickly observe a division between a small number of commonly detected species (Candida yeasts, Saccharomyces and yeasts in the Dipodascaceae, and Malassezia species) and a long tail of taxa that have been reported only once. Furthermore, an investigation into the ecology of these rare species reveals that many of them are incapable of colonization or long-term persistence in the gut. This paper examines what we know and have yet to learn about the fungal component of the gut microbiome, or "mycobiome", and an overview of methods. We address the potential of the field while introducing some caveats and argue for the necessity of including mycologists in mycobiome studies.

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Section: Discussionmentioning

confidence: 99%

The human gut mycobiome: pitfalls and potentials--a mycologists perspective

2015

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“…Antibiotic treatment or the use of germfree gnotobiotic animals enhances consistent colonization of the gut (81). In terms of innate immunity, mice with congenital granulocytic cell deficiencies are susceptible to GI candidiasis but mount C. albicans-specific adaptive responses and eventually clear the infection (106).…”

Section: Non-cd4mentioning

confidence: 99%

“…2D). While this has been demonstrated using murine models (81), monitoring human C. albicans intestinal colonization levels is more problematic. However, more recent clinical studies examining fecal loads have demonstrated increased Candida levels with antibotic treatment (101).…”

Section: Non-cd4mentioning

confidence: 99%

Candida albicans Pathogenesis: Fitting within the Host-Microbe Damage Response Framework

et al. 2016

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f Historically, the nature and extent of host damage by a microbe were considered highly dependent on virulence attributes of the microbe. However, it has become clear that disease is a complex outcome which can arise because of pathogen-mediated damage, host-mediated damage, or both, with active participation from the host microbiota. This awareness led to the formulation of the damage response framework (DRF), a revolutionary concept that defined microbial virulence as a function of host immunity. The DRF outlines six classifications of host damage outcomes based on the microbe and the strength of the immune response. In this review, we revisit this concept from the perspective of Candida albicans, a microbial pathogen uniquely adapted to its human host. This fungus commonly colonizes various anatomical sites without causing notable damage. However, depending on environmental conditions, a diverse array of diseases may occur, ranging from mucosal to invasive systemic infections resulting in microbe-mediated and/or host-mediated damage. Remarkably, C. albicans infections can fit into all six DRF classifications, depending on the anatomical site and associated host immune response. Here, we highlight some of these diverse and site-specific diseases and how they fit the DRF classifications, and we describe the animal models available to uncover pathogenic mechanisms and related host immune responses.

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“…In mice, a pioneering study was conducted by Cutler's research group showing that animals fed with antibiotic-containing water were stably colonized by the fungus (60). Other studies have largely confirmed and expanded on the mechanisms of Candida colonization in these mice, with no data reported, however, on vaginal colonization and infection (59,(61)(62)(63). Since antibiotic treatment is a well-known risk factor for vaginal candidiasis in women, this model should be characterized by some level of spontaneous susceptibility to vaginal candidiasis.…”

Section: Conclusion About the Relevance Of Rodent Models To Human DImentioning

confidence: 99%

Experimental Models of Vaginal Candidiasis and Their Relevance to Human Candidiasis

Cassone

Sobel

2016

Infect Immun

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bVulvovaginal candidiasis (VVC) is a high-incidence disease seriously affecting the quality of life of women worldwide, particularly in its chronic, recurrent forms (RVVC), and with no definitive cure or preventive measure. Experimental studies in currently used rat and mouse models of vaginal candidiasis have generated a large mass of data on pathogenicity determinants and inflammation and immune responses of potential importance for the control of human pathology. However, reflection is necessary about the relevance of these rodent models to RVVC. Here we examine the chemical, biochemical, and biological factors that determine or contrast the forms of the disease in rodent models and in women and highlight the differences between them. We also appeal for approaches to improve or replace the current models in order to enhance their relevance to human infection.A mong human diseases caused by Candida albicans, vulvovaginal candidiasis (VVC), especially in its chronic and recurrent forms (RVVC), is by far the most frequent. Recent epidemiological investigations have given a global estimate of RVVC incidence approaching 2%, which compares with the highest incidence of any single infectious disease on our planet (1). Although not a lethal disease, the quality of life of young women in their most socially and economically productive period can be truly devastated. Past and recent reviews highlight the dominant signs and symptoms of RVVC that make this chronic disease so devastating (2, 3). With the above premise, the magnitude of the efforts made by a number of investigators to identify disease mechanisms and host inflammatory and immune responses in vaginal candidiasis by adopting animal models of the disease is admirable. In some cases, the data obtained by the use of the models described above directed the investigators toward the choice of vaccine candidates or, more recently, toward devising novel therapeutic options based on the control of pathogenic vaginal inflammation (4-8). Overall, research has now progressed to promising future important applications for effective disease control (4). Nonetheless, it appears that some reflection is needed on the true nature of these models with respect to human disease, thus enhancing the relevance of the current data extrapolations from animal models and better defining the field of potential applications to humans. In this reflection, we succinctly consider the main factors which influence the success of Candida albicans as a vaginal pathogen, i.e., estrogens, commensalism, and immune-priming-tolerance axis, as well as the biochemical and microbiological properties of the vaginal environment. We also provide some suggestions that may be useful to overcome the shortcomings of the current models so as to improve or even replace them. A detailed review of the vast literature on RVVC and animal models of vaginal candidiasis is outside the scope of this paper, as is a review of studies made in human reconstituted vaginal epithelial cells (VEC). We do not discuss the other f...

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Murine Models of Candida Gastrointestinal Colonization and Dissemination

Cited by 107 publications

References 99 publications

The human gut mycobiome: pitfalls and potentials--a mycologists perspective

The human gut mycobiome: pitfalls and potentials--a mycologists perspective

Candida albicans Pathogenesis: Fitting within the Host-Microbe Damage Response Framework

Experimental Models of Vaginal Candidiasis and Their Relevance to Human Candidiasis

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