Host Sensing by Pathogenic Fungi.

The ability to cause disease extends from the ability to grow within the host environment. The human host provides a dynamic environment to which fungal pathogens must adapt to in order to survive. The ability to grow under a particular condition (i.e., the ability to grow at mammalian body temperature) is considered a fitness attribute and is essential for growth within the human host. On the other hand, some environmental conditions activate signaling mechanisms resulting in the expression of virulence factors, which aid pathogenicity. Therefore, pathogenic fungi have evolved fitness and virulence attributes to enable them to colonize and infect humans. This review highlights how some of the major pathogenic fungi respond and adapt to key environmental signals within the human host.

Adaptation of Candida albicans to environmental pH induces cell wall remodelling and enhances innate immune recognition.

Candida albicans is able to proliferate in environments that vary dramatically in ambient pH, a trait required for colonising niches such as the stomach, vaginal mucosal and the GI tract. Here we show that growth in acidic environments involves cell wall remodelling which results in enhanced chitin and ß-glucan exposure at the cell wall periphery. Unmasking of the underlying immuno-stimulatory ß-glucan in acidic environments enhanced innate immune recognition of C. albicans by macrophages and neutrophils, and induced a stronger proinflammatory cytokine response, driven through the C-type lectin-like receptor, Dectin-1. This enhanced inflammatory response resulted in significant recruitment of neutrophils in an intraperitoneal model of infection, a hallmark of symptomatic vaginal colonisation. Enhanced chitin exposure resulted from reduced expression of the cell wall chitinase Cht2, via a Bcr1-Rim101 dependent signalling cascade, while increased ß-glucan exposure was regulated via a non-canonical signalling pathway. We propose that this "unmasking" of the cell wall may induce non-protective hyper activation of the immune system during growth in acidic niches, and may attribute to symptomatic vaginal infection.