Premium
The Role of Yeast Urea Amidolyase in Patients with Suppressed Immune Systems (LB105)
Author(s) -
Cavins K.,
Alphin D.,
Braatz A.,
DeleonCamacho F.,
Emkay S.,
Flees H.,
Franitza A.,
Gerwig A.,
Groth E.,
Granlund L.,
Idell A.,
Klug L.,
Nakhla V.,
Osberg Z.,
Paniagua P.,
Wallner J.,
Rochon D.,
Fangmann J.,
St. Maurice Martin
Publication year - 2014
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.28.1_supplement.lb105
Subject(s) - immune system , candida albicans , hypha , yeast , microbiology and biotechnology , innate immune system , macrophage , chemistry , urea , biology , biochemistry , immunology , in vitro
According to Rice University, 70% of people are affected by the infectious fungus Candida albicans . The immune system uses T and B cells to stop pathogens. People with suppressed immune systems, such as children with transplants, AIDs or cancer patients, lack functional T and B cells, so they rely on macrophages to destroy Candida . Candida can kill and exit macrophages due to an enzyme: urea amidolyase (UAL) . While in the macrophage, Candida goes through a morphological switch from a sphere to a structure with hyphae due to an environment change. UAL converts urea to ammonia and CO 2 , creating an environment for hyphae to form, bursting the macrophage. The Greenfield SMART (Students Modeling A Research Topic) Team used 3D printing technology to model the four domains of UAL. The biotin carboxylase (BC) domain uses energy from ATP cleavage to attach CO 2 to the swinging arm portion, or biotin carboxyl carrier protein (BCCP) domain. The BCCP domain swings across UAL, attaching CO 2 to urea forming allophanate in the carboxyl transferase (CT) domain. Allophanate moves to the allophanate hydrolase (AH) domain, which hydrolyzes the allophanate into CO 2 and ammonia. Increases in CO 2 and ammonia cause hyphae to form, destroying macrophages and allowing Candida to spread. Since humans lack UAL, researchers could block UAL’s active sites to prevent Candida’s macrophage‐killing shape change, thus preventing systemic candidiasis without damaging human cells. Grant Funding Source : Supported by a grant from NIH‐CTSA.