Background The increasing rate of cancer cases is alarming. In 2018, 9.6 million people died of the disease (WHO 2020). Current treatments, such as chemical therapy using cisplatin (CisPt) as a basis, cause considerable collateral damage to the patient (Ahmad 2017). CisPt acts as an alkylating agent with affinity to DNA, binds to the guanine and cytosine residues, and prevents the processes of replication and transcription of the genetic material, resulting in cell death by apoptosis (Ahmad 2017). However, cisplatin is unable to differentiate between normal and cancerous cells. Moreover, cancer cells can develop
Entamoeba histolytica is a human pathogen, which can survive using haemoglobin (Hb) as only iron supply. Two probable haemophores (Ehhmbp26 and Ehhmbp45) are involved in iron acquisition in this parasite. However, mechanisms related to their transcriptional regulation have not been studied yet. In the present work, transcriptional profiles of both genes were evaluated in trophozoites cultures grown with different iron sources. ehhmbp26 gene was repressed totally by free iron, whereas ehhmbp45 gene showed clearly detectable mRNA levels. Expression profiles for both genes were significantly increased under iron privation condition. Interestingly, ehhmbp26 transcript was highly expressed by Holo-transferrin presence. This induction appears to be independent of direct contact between these proteins, because, in vitro assays evidenced that Ehhmbp26 protein was unable to bind this metalloprotein. Besides, in silico analysis of promoter nucleotide sequences of ehhmbp26 and ehhmbp45 genes revealed some distinctive core promoter elements described in E. histolytica and T-rich regions. Taking altogether these data suggest in E. histolytica dissimilar transcriptional mechanisms involved on iron acquisition control the expression of these genes, and they are unlike to those previously described for instance: in bacteria. Our findings evidenced this pathogen regulates the expression of ehhmbp26 and ehhmbp45 genes depending on the available iron supply, always ensuring the success of its infective process.
Introduction:Helicobacter pylori is a gram-negative spiral bacterial, it has been associated with peptic ulcers, gastritis, duodenitis, and it is believed to be the causative agent of gastric cancer. The sources such as human lactoferrin, haem and haemoglobin can support the H. pylori growth. However, is still not fully understood how the process of iron acquisition occurs. An in silico analysis has shown that H. pylori genome has a family of three outer membrane proteins regulated by iron (FrpB). Two of them: FrpB1 and FrpB2 were purified as recombinant proteins and their haem-or haemoglobin-binding capability was demonstrated. Unfortunately, the last protein of the family (FrpB3) has not been investigated. Methods: In this work FrpB3 was purified by haem-affinity chromatography and its capacity of haem-binding was analyzed. This protein was identified by mass spectrometry and its expression was quantified by real time technique under different human iron sources. This expression was compared with FrpB1 and FrpB2. The FrpB3 structure was analyzed by 3D model to view the motifs necessary for Hb-binding, and also was compared with FrpB1 and FrpB2 structures. Results: The protein identified was FrpB3, its respective gene was overexpressed with haemoglobin. FrpB1 was overexpressed with haem, while FrpB2 was induced in presence of haem and also haemoglobin. Both 3D models showed that they are structurally conserved because they have the typical barrel structure, which is inserted in membrane, also, the motifs necessary for Hb-binding were identified in all the structures. Conclusion: H. pylori expresses FrpB1, FrpB2 and FrpB3 proteins to scavenge iron and they are regulated according to availability of iron source, maybe in order to withstand the extreme environment present in the stomach. Our overall results represent the effort to explain the importance of iron acquisition.All human pathogens bacteria require iron for their metabolism and survival [7]. They need iron to catalyze several metabolic processes such as respiratory chain [8] and infectious processes [9]. However, in the human, free iron source is insufficient for J o u rnal of B a c te rio logy & P a ra sitolo g y Citation: González-López MA, Sánchez-Cruz C, Olivares-Trejo JJ (2019) Identification and characterization of a family of outer membrane proteins of Helicobacter pylori, which scavenge iron from human sources. J Bacteriol Parasitol. 10:355. 45. Elloumi H, Sabbah M, Debbiche A, Ouakaa A, Bibani N, Trad D, et al. Systematic gastric biopsy in iron deficiency anaemia. Arab J Gastroenterol. 2017;18(4):224-227.González-López MA et al.
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