UNASSIGNED: @entity5132 is a dimorphic fungus that colonizes @entity1 mucosal surfaces with the potential to cause life-threatening @entity3 . Studies on @entity6923 in a @entity19 @entity281 model using in vivo real-time bioluminescence imaging revealed persistence of @entity5132 in the @entity1085 under antifungal therapy. Preliminary analyses showed that bile conferred resistance against a wide variety of antifungals enabling survival in this cryptic host niche. Here, bile and its components were studied for their ability to reduce antifungal efficacy in order to elucidate the underlying mechanism of protection. While unconjugated @entity3645 were toxic to @entity5132 , @entity2226 , or @entity8959 conjugated @entity3645 were well tolerated and protective against @entity11794 and @entity2379 when exceeding their critical micellar concentration. Microarray experiments indicated that upregulation of genes generally known to mediate antifungal protection is not involved in the protection process. In contrast, @entity19501 and @entity1686 in- and efflux experiments indicated encapsulation of antifungals in micelles, thereby reducing their bioavailability. Furthermore, @entity37389 sensing was abolished in the presence of conjugated @entity3645 trapping @entity5132 cells in the hyphal morphology. This suggests that bioavailability of amphiphilic and hydrophobic compounds is reduced in the presence of bile. In contrast, small and hydrophilic molecules, such as @entity1880 , @entity4895 , or @entity4627 kept their antifungal properties. We therefore conclude that treatment of @entity1085 and bile duct infections is hampered by the ability of @entity3645 to encapsulate antifungals in micelles. As a consequence, treatment of @entity1085 or bile duct infections should favor the use of small hydrophilic drugs that are not solubilised in micelles.

Encapsulation of Antifungals in Micelles Protects @entity5132 during XXXX .

@entity1 :: ('9606', 'Species') :: ['human'] @entity2226 :: ('MESH:D013654', 'Chemical') :: ['taurine'] @entity1085 :: ('MESH:D005705', 'Disease') :: ['gall bladder'] @entity8959 :: ('D005998', 'Chemical') :: ['glycine'] @entity6923 :: ('MESH:C536777', 'Disease') :: ['systemic candidiasis'] @entity2379 :: ('MESH:D000666', 'Chemical') :: ['amphotericin B'] @entity19 :: ('10090', 'Species') :: ['murine'] @entity1880 :: ('MESH:D003513', 'Chemical') :: ['cycloheximide'] @entity1686 :: ('MESH:D005840', 'Chemical') :: ['crystal violet'] @entity4895 :: ('MESH:D005437', 'Chemical') :: ['flucytosine'] @entity5132 :: ('5476', 'Species') :: ['Candida albicans', 'C. albicans'] @entity281 :: ('MESH:D007239', 'Disease') :: ['infection'] @entity37389 :: ('MESH:D005204', 'Chemical') :: ['farnesol'] @entity3 :: ('MESH:D009362', 'Disease') :: ['invasive candidiasis'] @entity3645 :: ('MESH:D001647', 'Chemical') :: ['bile salts'] @entity19501 :: ('CHEBI:52672', 'Chemical') :: ['rhodamine 6G'] @entity4627 :: ('MESH:D019810', 'Chemical') :: ['sodium azide'] @entity11794 :: ('MESH:C105417', 'Chemical') :: ['caspofungin']
@entity1085 :: (MESH:D005705,Disease) :: ['Gall-Bladder Infection']
