Candida albicans iron acquisition within the host

Abstract

As a commensal and opportunistic pathogen, Candida albicans possesses a range of determinants that contribute to survival, persistence and virulence. Among this repertoire of fitness and virulence attributes are iron acquisition factors and pathways, which allow fungal cells to gain this essential mineral in the iron-poor environment of the host. The aim of this review is to present the strategies used by C. albicans to exploit host iron reservoirs and their impact on C. albicans pathogenicity. Because iron in the human host is mostly linked to host proteins, pathogens such as C. albicans must possess mechanisms to gain iron from these proteins. Here, we introduce the most important groups of human proteins, including haemoglobin, transferrin, lactoferrin and ferritin, which contain iron and that are potential iron sources for invading microorganisms. We then summarize and discuss the known and proposed strategies by which C. albicans exploits or may exploit iron from host proteins and compare these with strategies from other pathogenic microorganisms.

Iron acquisition in the cystic fibrosis lung and potential for novel therapeutic strategies

“…Despite reports of the inhibitory effects of lactoferrin and transferrin on pathogenic fungi (Almeida et al, 2009;Caza & Kronstad, 2013), Candida albicans and Aspergillus fumigatus can both utilize transferrin bound iron for growth using different mechanisms (Ramanan & Wang, 2000;Hissen et al, 2004). Siderophores are not involved in iron acquisition by Candida albicans; rather direct contact of Candida albicans with transferrin is required.…”

Cap2-HAP Complex Is a Critical Transcriptional Regulator That Has Dual but Contrasting Roles in Regulation of Iron Homeostasis in Candida albicans

“…Thus, the ability of C. albicans to acquire iron becomes critical for its survival as well as for pathogenesis (31). As in S. cerevisiae, there are multiple pathways for iron uptake in C. albicans as well, including high-affinity uptake, siderophore uptake, and heme uptake (32)(33)(34)(35). Previous reports showed that FTR1 is required for C. albicans pathogenesis (33).…”

“…The C. albicans genome contains genes encoding siderophore transporter, four iron permeases, five multicopper oxidases, a family of 17 putative ferric reductases, as well as heme uptake components indicating the multiplicity of iron acquisition pathways (28,32). C. albicans can also acquire iron from ferritin in a manner dependent on the Als3 protein (36), but, iron acquisition through Als3/ferritin does not exist in S. cerevisiae.…”

“…We retrieved the low iron_versus_high iron (L_H_Fe) microarray data of Lan et al (14), and a list of all 133 genes annotated in CGD (downloaded April 21, 2010) bearing the keyword "iron," plus five additional genes CSA1, CSA2, PGA7, FRE9, and orf19.867, related to iron homeostasis (32). Comparison of the three datasets showed that 33 genes were up-regulated in L_H_Fe data and showed Cap2 dependence.…”

Iron restriction-induced adaptations in the wall proteome of Candida albicans

“…Although ferritin is extremely resistant to microbial exploitation, C. albicans is able to use it as an iron source through the glycosylphosphatidylinositol (GPI)-anchored cell wall protein Als3, which not only functions as an adhesin and invasin but also serves as the receptor for ferritin (Almeida et al, 2008). To release and use iron from transferrin and ferritin or to exploit free environmental iron, C. albicans employs the reductive pathway, as reviewed by Almeida et al (2009). First, plasma membrane-located ferric reductases, like Fre10 and Cfl1, reduce ferric iron (Fe 3+ ) to the more soluble ferrous form (Fe 2+ ) (Knight et al, 2005;Yamada-Okabe et al, 1996).…”