<p>We are studying two hemoglobin-induced genes <I>HBR1</I>and <I>HMX1</I>, a Candida heme oxygenase. Heme oxygenase converts heme to biliverdin and carbon monoxide. Biliverdin is increasing used to inhibit inflammatory responses associated with organ transplantation, but sources for this compound are limited. We developed a method to efficiently produce biliverdin using the heme oxygenase activity in <I>C. albicans</I>and obtained a patent for this method. We also found that a <I>HMX1</I>null strain of <I>C. albicans</I>has decreased virulence in a murine model of disseminated candidiasis. Reconstitution of one or both deleted alleles restores virulence to the level of wild type. Initial organ burdens in infected mice are not decreased for the null strain, indicating that early growth in the host is not impaired due to loss of this pathway for scavenging iron. In contrast, levels of several regulatory cytokines and chemokines are decreased in mice infected with null cells, and initial lesions in the kidney caused by the null mutant are more rapidly cleared following PMN infiltration. Collectively, these results show that <I>C. albicans</I>Hmx1 expression limits the host immune response to candidemia and contributes to disease progression.</P><p>We are studying two hemoglobin-induced genes <I>HBR1</I>and <I>HMX1</I>, a Candida heme oxygenase. Heme oxygenase converts heme to biliverdin and carbon monoxide. Biliverdin is increasing used to inhibit inflammatory responses associated with organ transplantation, but sources for this compound are limited. We developed a method to efficiently produce biliverdin using the heme oxygenase activity in <I>C. albicans</I>and obtained a patent for this method. We also found that a <I>HMX1</I>null strain of <I>C. albicans</I>has decreased virulence in a murine model of disseminated candidiasis. Reconstitution of one or both deleted alleles restores virulence to the level of wild type. Initial organ burdens in infected mice are not decreased for the null strain, indicating that early growth in the host is not impaired due to loss of this pathway for scavenging iron. In contrast, levels of several regulatory cytokines and chemokines are decreased in mice infected with null cells, and initial lesions in the kidney caused by the null mutant are more rapidly cleared following PMN infiltration. Collectively, these results show that <I>C. albicans</I>Hmx1 expression limits the host immune response to candidemia and contributes to disease progression.</P>
Showing the most recent 10 out of 12 publications