Entamoeba histolytica secretes two haem-binding proteins to scavenge haem

Abstract

Entamoeba histolytica is a human pathogen which can grow using different sources of iron such as free iron, lactoferrin, transferrin, ferritin or haemoglobin. In the present study, we found that E. histolytica was also capable of supporting its growth in the presence of haem as the sole iron supply. In addition, when trophozoites were maintained in cultures supplemented with haemoglobin as the only iron source, the haem was released and thus it was introduced into cells. Interestingly, the Ehhmbp26 and Ehhmbp45 proteins could be related to the mechanism of iron acquisition in this protozoan, since they were secreted to the medium under iron-starvation conditions, and presented higher binding affinity for haem than for haemoglobin. In addition, both proteins were unable to bind free iron or transferrin in the presence of haem. Taken together, our results suggest that Ehhmbp26 and Ehhmbp45 could function as haemophores, secreted by this parasite to facilitate the scavenging of haem from the host environment during the infective process.

Make It, Take It, or Leave It: Heme Metabolism of Parasites

“…Although no heme protein is listed in Table 1 for Entamoeba , this amoeboid human parasite secretes two proteins that bind heme in vitro. However, they were suggested to scavenge for heme not for heme itself but because of the requirement for iron [22]. Thus the possibility remains that this anaerobe is totally devoid of heme proteins.…”

Gene Expression Profiling in Entamoeba histolytica Identifies Key Components in Iron Uptake and Metabolism

“…cues for iron uptake, utilization and storage in E. histolytica ). Entamoeba histolytica has hemophore-like proteins [14] and receptors for transferrin and lactoferrin [13]. The mechanisms of heme-hemophore and iron-siderophore uptake and the subsequent iron utilization and storage have not been described.…”

“…On the basis of our current knowledge of iron uptake and metabolism in E. histolytica , we propose the following hypotheses: (i) E. histolytica is able to obtain iron and heme via phagocytosis and directly from host proteins through import mediated by hemophores [14] and siderophores; (ii) transporter and trafficking proteins (e.g., P-glycoprotein 5 proteins, ABC transporters and MFTs) are involved in the internalization and salvaging of iron/heme, as observed for Leishmania [34], [58]; (iii) within the cell, iron ions may be released from these complexes through the action of monooxygenase and cysteine proteinases; and (iv) E. histolytica maintains a balance between free and protein-bound iron ions using Fe-S clusters. Experimental validation of these hypotheses is now required to confirm the roles of these factors in iron uptake and metabolism in E. histolytica.…”

“…The monooxygenase heme oxygenase degrades heme and releases iron; we suggest that a monooxygenase (EHI_009840) could be responsible for heme degradation in E. histolytica. (III) Heme can also be scavenged by secreted hemophores such as hemoglobin-binding proteins 45 and 26 (Ehhmbp 45 and Ehhmbp 26), which are able to bind Hb and heme [14]. However, the mechanisms of hemophore export and heme-hemophore complex uptake are unknown (blue dashed arrows).…”

“…However, the fact that hemolytic activities have been detected in E. histolytica trophozoites [13] suggests that the parasites might be able to lyse red blood cells (RBCs) and liberate the host's heme via an non-phagocytic route. Furthermore, it has been suggested that two heme-binding proteins secreted by E. histolytica facilitate the scavenging of host heme [14]. Little is known about iron uptake, utilization and storage pathways in E. histolytica , with the exception of a few enzymes (i.e., NifS, NifU and rubrerythrin) involved in Fe-S cluster pathways [15], [16].…”