Surviving Deadly Lung Infections: Innate Host Tolerance Mechanisms in the Pulmonary System
Much research on infectious diseases focuses on clearing the pathogen through the use of antimicrobial drugs, the immune response, or a combination of both. Another way to survive an infection is to tolerate the alterations to homeostasis that occur during a disease state through a process called host tolerance or resilience, which is independent from pathogen burden. Alterations in homeostasis during infection are numerous and include tissue damage, increased inflammation, metabolic changes, temperature changes, and changes in respiration. By understanding tolerance mechanisms in the lung we can better address treatment options for deadly pulmonary infections.
Congratulations to Jenna Wurster who has received an NSF Fellowship Award for her work in the Belenky Lab!
Congratulations to Benjamin Korry who has received an NSF Fellowship Award for his work in the Belenky Lab!
Microbial competition between Escherichia coli and Candida albicans reveals a soluble fungicidal factor
Localized and systemic fungal infections caused by Candida albicans can lead to significant mortality and morbidity. However, severe C. albicans infections are relatively rare, occurring mostly in the very young, the very old, and immunocompromised individuals. The fact that these infections are rare is interesting because as much as 80 percent of the population is asymptomatically colonized with C. albicans. It is thought that members of the human microbiota and the immune system work in concert to reduce C. albicans overgrowth through competition and modification of the growth environment. Here, we report that Escherichia coli (strain MG1655) outcompetes and kills C. albicans (strain SC5314) in vitro. We find that E. coli produces a soluble factor that kills C. albicans in a magnesium-dependent fashion such that depletion of available magnesium is essential for toxicity.
A central theme in biology is to understand how different signaling outputs can be accomplished by changes to signal transduction pathways. Here, we examined epigenetic differences between two cell states in the human fungal pathogen Candida albicans. We show that cells in the “white” state are sterile due to multiple bottlenecks in MAPK signaling relative to mating-competent “opaque” cells. Alleviation of these bottlenecks by reverse engineering effectively converts sterile white cells into sexually competent cells. These results have broad implications for understanding how epigenetic changes can impact MAPK expression and signaling output, including events associated with tumorigenesis. We also propose a model for how the white-opaque switch gained control of sexual reproduction in Candida during evolution.