Isolation and characterization of equine NRAMP1: a candidate gene for natural resistance to Rhodococcus equi

Abstract

Despite the widespread use of current disease control methods, significant losses due to intracellular bacterial diseases still plague the livestock industry worldwide. Many programs have been established in an attempt to combat these deadly diseases, some of which also pose a threat to public health. One such bacterium that is particularly harmful to horses is Rhodococcus equi, previously known as Corynebacterium equi, which causes severe pneumonia in foals and immunocompromised humans. Infected animals show very few symptoms early in the course of disease and currently there is no definitive diagnostic test for early detection, thus allowing the disease to progress virtually undetected until it has caused significant lung damage. In recent years, genetically based natural disease resistance has been intensively studied as a viable option for controlling diseases caused by intracellular bacteria such as R. equi. One gene commonly associated with natural disease resistance against intracellular pathogens is NRAMP1. It has been identified in several species and appears to be a highly conserved gene. After sequencing the majority of the equine cDNA homolog of NRAMP1, analysis of the gene reveals that the predicted protein consists of 12 transmembrane domains with an SH3 binding domain in the amino terminus, 4 protein kinase C sites, 1 N-linked glycosylation site and a conserved 20 amino acid transport motif. Equine NRAMP1 is approximately 90% homologous to the bovine and human sequences and 83% homologous to the murine sequence.