Iron at the Centre of Candida albicans Interactions

Abstract

Iron is an absolute requirement for both the host and most pathogens alike and is needed for normal cellular growth. The acquisition of iron by biological systems is regulated to circumvent toxicity of iron overload, as well as the growth deficits imposed by iron deficiency. In addition, hosts, such as humans, need to limit the availability of iron to pathogens. However, opportunistic pathogens such as Candida albicans are able to adapt to extremes of iron availability, such as the iron replete environment of the gastrointestinal tract and iron deficiency during systemic infection. C. albicans has developed a complex and effective regulatory circuit for iron acquisition and storage to circumvent iron limitation within the human host. As C. albicans can form complex interactions with both commensal and pathogenic co-inhabitants, it can be speculated that iron may play an important role in these interactions. In this review, we highlight host iron regulation as well as regulation of iron homeostasis in C. albicans. In addition, the review argues for the need for further research into the role of iron in polymicrobial interactions. Lastly, the role of iron in treatment of C. albicans infection is discussed.

Association of severe early childhood caries with salivary ferritin

“…[ 5 12 13 ] Recent studies have shown that iron is at the center of interaction for C.albicans and ferritin plays a key role in it. [ 14 ] C. albicans has shown multiple approaches to acquire iron from the host and ferritin has promoted the process. [ 15 ] Children with high C. albicans count have five times higher chance to develop ECC compared to those without C. albicans ,[ 16 ] suggesting potent cariogenic characteristics, which lead to the development and progression of S-ECC.…”

Iron Assimilation during Emerging Infections Caused by Opportunistic Fungi with emphasis on Mucorales and the Development of Antifungal Resistance

“…Consequently, the ability of a fungal pathogen to sequester iron from different host iron-containing proteins for growth and proliferation is a key virulence determinant [81]. It has been thoroughly demonstrated that C. albicans has a mechanism to obtain iron from haem and haemoglobin that is independent of both the reductive and non-reductive systems, i.e., xenosiderophore transport [82,83]. The ability to utilise haem/haemoglobin depends on the conserved family of common in several fungal extracellular membrane proteins or CFEM proteins, which has an eight cysteine-containing domain: Rbt5, Rbt51/Pga10, Pga7, and the secreted haemophore, Csa2 [81,[84][85][86][87][88][89].…”

Fungal factors involved in host immune evasion, modulation and exploitation during infection

“…xenosiderophores (e.g., ferricrocin), extensively reviewed in studies by Fourie, Kuloyo, Mochochoko, Albertyn, and Pohl (2018) and Gerwien et al (2018). The already mentioned invasin Als3, required for induced endocytosis, is also crucial for acquiring iron from ferritin, which is the main iron storage protein in oral epithelial cells (Almeida et al, 2008).…”