The game theory of Candida albicans colonization dynamics reveals host status-responsive gene expression.

BACKGROUND: The fungal pathogen Candida albicans colonizes the gastrointestinal (GI) tract of mammalian hosts as a benign commensal. However, in an immunocompromised host, the fungus is capable of causing life-threatening infection. We previously showed that the major transcription factor Efg1p is differentially expressed in GI-colonizing C. albicans cells dependent on the host immune status. To understand the mechanisms that underlie this host-dependent differential gene expression, we utilized mathematical modeling to dissect host-pathogen interactions. Specifically, we used principles of evolutionary game theory to study the mechanism that governs dynamics of EFG1 expression during C. albicans colonization. RESULTS: Mathematical modeling predicted that down-regulation of EFG1 expression within individual fungal cells occurred at different average rates in different hosts. Rather than using relatively transient signaling pathways to adapt to a new environment, we demonstrate that C. albicans overcomes the host defense strategy by modulating the activity of diverse fungal histone modifying enzymes that control EFG1 expression. CONCLUSION: Based on our modeling and experimental results we conclude that C. albicans cells sense the local environment of the GI tract and respond to differences by altering EFG1 expression to establish optimal survival strategies. We show that the overall process is governed via modulation of epigenetic regulators of chromatin structure.

Method and apparatus for intra-esophageal cough detection.

Gastro-esophageal reflux disease (GERD) is a common cause of chronic cough. However, a low-cost diagnostic tool for linking GERD and cough in a cause and effect relationship is still lacking. In the present study, an intra-esophageal cough detection probe that comprises a miniature white-light interferometric fiber optic pressure sensor is proposed. This innovative catheter provides a custom encapsulation of the pressure sensor which specifically optimizes the sensitivity to pressure responses triggered by cough events. In vitro and in vivo testing results of the initial cough detection probe are presented. Experimental results demonstrated the feasibility of using the proposed catheter for identifying cough episodes. The presented work can be integrated with commercial reflux pH/impedance probes to facilitate simultaneous 24-hour ambulatory monitoring of cough and reflux events, with the ultimate goal of quantifying the temporal correlation between the two types of events.