scholarly journals Typhoid Fever and Genetic Polymorphisms at the Natural Resistance–Associated Macrophage Protein 1

2001 ◽  
Vol 183 (7) ◽  
pp. 1156-1160 ◽  
Author(s):  
Sarah J. Dunstan ◽  
Vo An Ho ◽  
Chau Minh Duc ◽  
Mai Ngoc Lanh ◽  
Cao Xuan Thanh Phuong ◽  
...  
Keyword(s):  
Typhoid Fever ◽  
Genetic Polymorphisms ◽  
Natural Resistance ◽  
Macrophage Protein

scholarly journals Natural resistance-associated macrophage protein 1 gene polymorphisms in thalassemia patients with tuberculosis infection

2016 ◽  
Vol 56 (2) ◽  
pp. 84 ◽  
Author(s):  
Mohammad Ghozali ◽  
Sari Puspa Dewi ◽  
Reni Ghrahani ◽  
Ani Melani Maskoen ◽  
Lelani Reniarti ◽  
...  
Keyword(s):  
Genetic Polymorphisms ◽  
Gene Polymorphisms ◽  
Serum Iron ◽  
Binding Capacity ◽  
Iron Status ◽  
Major Gene ◽  
Natural Resistance ◽  
Cross Sectional ◽  
Metal Transporter ◽  
Macrophage Protein

that needs regular blood transfusions leading to accumulation of iron in the cells. This iron overload level in macrophage might cause intracellular bacteria, particularly Mycobacterium tuberculosis (MTB) to multiply. Polymorphisms in natural resistance-associated macrophage protein 1 (NRAMP1), a metal transporter across the phagosome membrane, play important role in regulating iron, which is also needed by MTB. Increased iron in thalassemia patients may have an increased potential risk for TB.Objective To compare natural resistance-associated macrophage protein 1 (NRAMP1) gene polymorphisms (INT4, D543N, and 3’UTR) in thalassemia patients with and without tuberculosis (TB) infection.Methods A cross-sectional measurement of NRAMP1 genetic polymorphisms was performed in pediatric thalassemia patients with TB (n=40) and without TB (n=50). Iron status including serum iron, total iron-binding capacity (TIBC), and ferritin, was compared between the two groups. The NRAMP1 genetic polymorphisms were analysed using polymerase chain reaction/restriction fragment length polymorphism (PCR/RFLP). Allelic and genotypic distributions of each polymorphism were assessed for possible associations with TB infection.Results Mean serum iron and TIBC in thalassemia patients with TB were higher compared to thalassemia patients without TB (mean serum: 166.26 vs. 134.92 μmol/L, respectively; P=0.026) and (mean TIBC: 236.78 vs. 195.84 μmol/L, respectively; P=0.029). In thalassemia patients with TB, we observed significantly higher frequency of the C allele in INT4 (10% vs. 2%, respectively; OR=5.44; 95%CI 1.1 to 26.4; P=0.02) and the TGTG deletion allele (78.8% vs. 51%, respectively; OR=3.56; 95%CI 1.83 to 6.9; P=0.0002) in 3’UTR polymorphisms than in thalassemia patients without TB. There were no significant differences in distributions of the A allele between TB and non-TB groups (16.3% vs. 15%, respectively; P=0.84) or the GA genotype (32.5% vs. 30%, respectively; P=0.79) in D543N.Conclusion The NRAMP1 polymorphisms are known to be associated with major gene susceptibility to TB, and in our thalassemia patients this association is even more pronounced.

scholarly journals Natural Resistance Associated Macrophage Protein-1 Expression in Salmonella typhi Infection with Acute Recurrence State of Typhoid Fever in Endemic Areas, Indonesia

2020 ◽  
pp. 1-10
Author(s):  
Ade Rifka Junita ◽  
Firdaus Hamid ◽  
Rosdiana Natzir ◽  
Rosana Agus ◽  
Burhanuddin Bahar ◽  
...  
Keyword(s):  
Typhoid Fever ◽  
Clinical Symptoms ◽  
Salmonella Typhi ◽  
Host Susceptibility ◽  
Natural Resistance ◽  
Enzyme Linked Immunosorbent Assay ◽  
Primary Health ◽  
The Mean ◽  
Macrophage Protein ◽  
Healthy Persons

Background and Aim: The molecular pathogenesis of typhoid fever is complex and the host susceptibility mechanisms such as Natural Resistance Associated Macrophages Protein-1 (NRAMP-1) are poorly understood. This study explores the expression of NRAMP-1 in the serum of Acute Recurrence State (ARS) of typhoid fever compared with typhoid fever patients and healthy persons. Methods: Thirty of ARS of typhoid fever and 30 typhoid fever patients were collect from several Primary Health Care and Hospitals in the endemic area. Diagnosis of typhoid fever based on clinical symptoms and confirmed by blood culture. Healthy persons were collect from the Blood Transfusion Unit, Makassar, Indonesia. The expression of NRAMP-1 was determined using Enzyme-linked immunosorbent assay (ELISA). Results: The mean of NRAMP-1 expression in 30 ARS of typhoid fever and 30 typhoid fever were found 10.941,56 pg/mL and 11.027,65 pg/mL, respectively. However, the mean of NRAMP-1 expression in healthy persons was found 21.103,91 pg/mL. Conclusion: No different the expression of NRAMP-1 in ARS of typhoid fever compared with typhoid fever patients. However, expression of NRAMP-1 in both ARS of typhoid fever and typhoid fever showed significantly lower than healthy persons. Future study is needed to explore the other molecular factors involved to become ARS.

scholarly journals Mycobacterium tuberculosis Expresses a Novel Ph-Dependent Divalent Cation Transporter Belonging to the Nramp Family

1999 ◽  
Vol 190 (5) ◽  
pp. 717-724 ◽  
Author(s):  
Daniel Agranoff ◽  
Irene M. Monahan ◽  
Joseph A. Mangan ◽  
Philip D. Butcher ◽  
Sanjeev Krishna
Keyword(s):  
Mycobacterium Tuberculosis ◽  
Metal Ion ◽  
Divalent Cations ◽  
Natural Resistance ◽  
Xenopus Laevis Oocytes ◽  
Mrna Levels ◽  
Susceptibility To Infection ◽  
Reverse Transcription Pcr ◽  
Acidic Extracellular Ph ◽  
Macrophage Protein

Mammalian natural resistance–associated macrophage protein (Nramp) homologues are important determinants of susceptibility to infection by diverse intracellular pathogens including mycobacteria. Eukaryotic Nramp homologues transport divalent cations such as Fe2+, Mn2+, Zn2+, and Cu2+. Mycobacterium tuberculosis and Mycobacterium bovis (bacillus Calmette-Guérin [BCG]) also encode an Nramp homologue (Mramp). RNA encoding Mramp induces ∼20-fold increases in 65Zn2+ and 55Fe2+ uptake when injected into Xenopus laevis oocytes. Transport is dependent on acidic extracellular pH and is maximal between pH 5.5 and 6.5. Mramp-mediated 65Zn2+ and 55Fe2+ transport is abolished by an excess of Mn2+ and Cu2+, confirming that Mramp interacts with a broad range of divalent transition metal cations. Using semiquantitative reverse transcription PCR, we show that Mramp mRNA levels in M. tuberculosis are upregulated in response to increases in ambient Fe2+ and Cu2+ between <1 and 5 μM concentrations and that this upregulation occurs in parallel with mRNA for y39, a putative metal-transporting P-type ATPase. Using a quantitative ratiometric PCR technique, we demonstrate a fourfold decrease in Mramp/y39 mRNA ratios from organisms grown in 5–70 μM Cu2+. M. bovis BCG cultured axenically and within THP-1 cells also expresses mRNA encoding Mramp. Mramp exemplifies a novel prokaryotic class of metal ion transporter. Within phagosomes, Mramp and Nramp1 may compete for the same divalent cations, with implications for intracellular survival of mycobacteria.

Transcriptional control of Nramp1: a paradigm for the repressive action of c-Myc

2004 ◽  
Vol 32 (6) ◽  
pp. 1084-1086 ◽  
Author(s):  
A.S. Lapham ◽  
E.S. Phillips ◽  
C.H. Barton
Keyword(s):  
Transcriptional Control ◽  
Cell Activation ◽  
Zinc Finger Protein ◽  
Specific Binding ◽  
Divalent Cations ◽  
Natural Resistance ◽  
Finger Protein ◽  
Late Endosomes ◽  
Solute Carrier ◽  
Macrophage Protein

Slc11a1/Nramp1 (solute carrier family 11 member a1/murine natural resistance-associated macrophage protein 1 gene) encodes a divalent cation transporter that resides within lysosomes/late endosomes of macrophages. Nramp1 modulates the cellular distribution of divalent cations in response to cell activation by intracellular pathogens. Nramp1 expression is repressed and activated by the proto-oncogene c-Myc and Miz-1 (c-Myc-interacting zinc finger protein 1) respectively. Here we demonstrate, using a c-Myc mutant (V394D, Val394→Asp) that is incapable of binding Miz-1, that c-Myc repression of Nramp1 transcription is dependent on its interaction with Miz-1. An oligo pull-down assay demonstrates specific binding of recombinant Miz-1 to the Nramp1 Miz-1-binding site or initiator element(s), and Miz-1-dependent c-Myc recruitment.

Sign in / Sign up

Export Citation Format

Share Document