An Introduction to the Influence of Nutritional Factors on the Pathogenesis of Opportunist Fungal Pathogens in Humans

Abstract

Fungi such as Aspergillus fumigatus, Candida albicans, and Cryptococcus neoformans are opportunistic pathogens in humans. They usually infect individuals whose immune system is compromised due to either a primary infection, e.g., HIV/AIDS, or as part of treatment for another condition, e.g., stem cell or solid organ transplant. In hosts with a weakened immune system, these fungi can cause life-threatening infections. Unlike true pathogens, opportunistic pathogens do not have specific mechanisms to overcome a healthy host, requiring a different approach to understand how they cause infection. The ability of fungi to adapt to various environmental conditions, including the human host, is critical for virulence. In humans, micronutrient metals, such as iron, are sequestered to reduce serum concentrations, which helps to inhibit microbial growth. Other human tissues may increase metal concentrations to toxic levels to prevent infection by pathogens. The ability of fungi to acquire or detoxify nutrients, such as iron or copper, from the host is essential for the establishment of infection. In this review, the role of fungal nutrition will be discussed in relation to opportunistic fungal pathogens. It will focus on the acquisition of micronutrients, e.g., iron, copper, and zinc, and how this enables these fungi to circumvent host nutritional immunity.

Keywords: aspergillosis; fungal nutrition; mycosis; virulence.

Figure 1

Summary of the challenges faced by opportunist pathogenic fungi in the environment and in the human host. The red and blue arrows in the microbial competition section indicate interactions between the fungal pathogen and environmental/host microbes.

Figure 2

Relationship between metal micronutrients and oxidative stress. Metal micronutrients and macronutrients, such as glucose, must be acquired from the environment and then imported into the cell. Respiration leads to the production of superoxide radicals, and these are detoxified by the enzyme superoxide dismutase (SOD), which requires Mn, Cu, or Zn as co-factors. Production of hydrogen peroxide by this reaction can react with excess Fe or Cu, leading to the Fenton reaction, which produces hydroxyl radicals leading to oxidative stress.