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Clinical Effects of Gamma-Radiation-Resistant Aspergillus sydowii on Germ-Free Mice Immunologically Prone to Inflammatory Bowel Disease

Authors: Atef S. Shehata, Pranab K. Mukherjee, Hassan N. Aboulatta, Atef I. El Akhras, Said H. Abbadi, and Mahmoud A. Ghannoum

Publication Year: 2016

PMID: 27630775

To date, there are a few studies reporting the severity of primary and disseminated gastrointestinal aspergillosis in immunocompromised hosts, including children [1] (see also references in [2]). Although aspergilloses are primarily confined to aerobic surfaces, systemic infections and rapid mortality are known to have occurred in humans and domestic animals [3], especially during disruption of the gastrointestinal barrier and associated microbiota (dysbiosis), which increases susceptibility to fatal systemic fungal infections [2]. Of all invasive fungal infections, aspergilloses account for 24% of human patients. With aspergillosis, one in every five patients develops fatal invasive infection.

Of epidemiological interest, we report a well-known fungal pathogen of marine corals and humans, Aspergillus sydowii, as an unwanted contaminant of a germ-free (GF) colony of SAMP/YitFc mice immunologically prone to suffer spontaneous inflammatory bowel disease (IBD; Crohn’s-like intestinal disease) and other multiorgan inflammatory complications. Such Crohn’s-like intestinal disease occurs in 100% mice in both specific pathogen-free (SPF) and germ-free conditions. Among the aspergilloses [3], A. sydowii is epidemiologically interesting because it is a pathogen known for causing mortality in Sea Fan corals (Gorgonia ventalina; animals that feed on plankton), threatening various Caribbean reefs since the 1990s [4], where it seems to remain geographically confined. Infections cause circular purple areas of necrosis and mortality that is not evidenced in other corals. Initially isolated from humans in the USA in 1989 from integumentary (e.g., skin and nails) infections [5], A. sydowii has been isolated in recent years from patients in other more distant regions (Czech Republic, Russia) [67].

Mice under germ-free conditions have a very high risk of exuberant infections by any commensal, pathogenic, or environmental microbes. Here we report a case of 125 germ-free SAMP/YitFc mice inadvertently exposed to A. sydowii via commercial germ-free grade irradiated contaminated feed. The (SAMP/YitFc) mice contaminated in this study were particularly deemed prone to A. sydowii opportunistic fungal infections because (i) they were germ-free and therefore lacked protective competitive surface microbial commensal flora (microbiota), in both gut and skin; (ii) the mouse genetic line is immunologically prone to progressive chronic intestinal inflammation, conjunctivitis, and ulcerative dermatitis; (iii) they have decrease clearance of pathogens like Salmonella enteritidis [8]; and (iv) because germ-free mice have no protective antibody-mediated adaptive (memory) immunity against microorganisms due to lack of exposure to commensal or pathogenic microbes when raised in germ-free conditions.

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