Treatment of vancomycin-resistant Enterococcus (VRE) infections is limited by the paucity of effective antibiotics. Administration of broad-spectrum antibiotics promotes VRE colonization by down-regulating homeostatic innate immune defenses. Intestinal epithelial cells and Paneth cells express antimicrobial factors upon direct or indirect stimulation of the Toll-like receptor (TLR)-MyD88-mediated pathway by microbe-derived molecules. Here, we demonstrate that the TLR5 agonist flagellin restores antibiotic-impaired innate immune defenses and restricts colonization with VRE. Flagellin stimulates the expression of RegIIIγ, a secreted C-type lectin that kills Gram-positive bacteria, including VRE. Systemic administration of flagellin induces RegIIIγ expression in intestinal epithelial cells and Paneth cells along the entire length of the small intestine. Induction of RegIIIγ requires TLR5 expression in hematopoietic cells and is dependent on IL-22 expression. Systemic administration of flagellin to antibiotic-treated mice dramatically reduces VRE colonization. By enhancing mucosal resistance to multi-drug resistant organisms, flagellin administration may provide a clinically useful approach to prevent infections in patients treated with broad-spectrum antibiotics.

Non-neoformans Cryptococcus species, including C. laurentii and C. albidus, have historically been classified as exclusively saprophytic. However, recent studies have increasingly implicated these organisms as the causative agent of opportunistic infections in humans. Herein, the case is presented of C. laurentii meningitis in a critically ill patient receiving corticosteroids. C. laurentii has been implicated in an additional 18 cases of opportunistic infection, predominantly of the skin, bloodstream, and central nervous system. The most clinically significant risk factors for non-neoformans cryptococcal infections include: impaired cell-mediated immunity, recent corticosteroid use, and invasive catheter placement. This article provides a comprehensive review of the clinical relevance, pathogenesis, risk factors, and treatment of non-neoformans Cryptococcus species.