The Mucorales are clinically important, opportunistic fungi that can cause mucormycosis, a life-threatening infection in immunocompromised and diabetic patients.  Infections with pathogenic Lichtheimia species as with other mucoralean fungi are known for its rapid progression, difficulties in diagnosis and limited therapeutic options, which accounts for the high mortality rates. One of the major risk factors for the development of mucormycosis is elevated serum iron levels. With iron being an essential trace metal for all living cells and its availability being restricted in the environment; fungi have developed different mechanisms to acquire iron. These include the reductive pathway, siderophore uptake systems and the utilisation of iron containing proteins. During infection, the availability of free iron is kept extremely low, with most of the iron bound to host proteins such as ferritin, transferrin and haemoglobin. This iron-withholding response is a recognised example of nutritional immunity and it is one of the main strategies used to restrict the growth of invading pathogens. Under these stress condition, human pathogenic fungi recruit these high affinity iron acquisition systems to overcome iron starvation inside the host. 
To date, our knowledge remains limited regarding iron metabolism in Lichtheimia corymbifera during infection. Since iron uptake is a key factor during infection; the aims of our current research are to determine the spectrum of iron sources our fungi can utilise in the environment and identify which host iron containing proteins L. corymbifera sequesters iron from. We also intend to identify which transcription factors are involved and gain insight into how these pathways are regulated. 
These will be accomplished by applying both molecular and physiological studies including heterologous gene expression, complementation assays, transcriptome analysis and comparative genomics. 

Comparative genomics of L. corymbifera has highlighted conserved genes involved in the three characterised pathways. This is particularly evident in the siderophore transporter genes which are highly conserved and cluster closely with other siderophore transporter genes from other fungal pathogens such as Aspergillus species. There are also unique features in several genes involved in iron acquisition which differ when compared with other opportunistic fungi. An example of which is the high copy number of genes belonging to the reductive iron uptake pathway. RNA sequencing data has indicated that these genes may have different functions and our work will focus on determining the functionality of these duplicated genes. Initial gene expression studies have highlighted an iron responsive transcription factor which shows sequence similarities to GATA-transcription factor which are known to be involved in iron regulation in other fungal pathogens. 

Answering these key questions will aid our understanding of how these iron-uptake systems contribute to virulence. Collectively, our findings have the potential to aid future research into the development of therapeutics.

5 / Lichtheimia corymbifera: elucidating the mechanisms for iron acquisition and transport during infection