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CO2 sensing proves critical for fungal pathogens to adapt to life in air and human hosts

whereas for C. neoformans, synthesis of a polysaccharide capsule is key.

In the bodies of mammals, the CO2 concentration is more than 150-fold higher (5%) than it is in atmospheric air (0.033%). Consequently, C. albicans and C. neoformans are exposed to dramatically elevated CO2 concentrations when causing systemic disease. In their research, the authors identify CO2 as a physiological signal that induces the pathogenic filamentous transition in C. albicans; they also demonstrate that an ancient group of enzymes called adenylyl cyclases are the so-called chemosensors mediating both the CO2 -dependent filamentation in C. albicans and the capsule biosynthesis in C. neoformans. The authors go on to show that CO2 sensing in C. albicans is essential for superficial (skin) infections, in which yeast must be able to grow despite significantly lowered CO2 levels present at the skin surface. Based on their findings, the authors conclude that CO2 sensing is a vital mediator of fungal virulence in different host environments--for example, at different sites within the body.

In a related paper, Joseph Heitman and colleagues, also using C. neoformans as a model system for understanding fungal disease, provide new evidence that CO2 sensing and metabolism govern growth, sexual reproduction, and virulence of this pathogenic microbe.

In this work, the researchers investigated the CO2-sensing mechanism of C. neoformans. This pathogen normally infects the human host (a high-CO2 environment) from the air (low CO2) in the course of causing deadly fungal meningitis. The authors found that an enzyme called carbonic anhydrase (CA) plays a critical role in the yeast's growth in ambient air; the CA enzyme accomplishes this by providing bicarbonate substrates for fatty-acid biosynthesis and other cellular processes. In contrast, the CA enzyme is dispensible for the yeast's survival in the high- CO2 environment of the host. Another major finding of the work is that f
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Source:Cell Press


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