Identification of novel drug targets for humans and potential vaccine targets for cattle by subtractive genomic analysis of Brucella abortus strain 2308

Abstract

Brucella abortus is the causative agent of brucellosis, a neglected endemic zoonotic disease. It causes devastating economic losses in low income and developing countries. Clinical symptoms of infected cows include abortion, poor weight, reduced fertility gain and reduction in milk production. Transmission of the zoonotic disease from cattle to human can occur through direct contact with infected cows, their tissues (e.g. placenta or aborted tissues), or their products (e.g. dairy) whereas human-to-human transmission can occur transplacentally or via breastfeeding. Malaise, fatigue, fever, arthritis are some clinical symptom of the disease in humans. Recent studies have revealed that Brucella abortus show resistance to several antibiotics. There are worldwide concerns about rising levels of antibiotic resistance resulting in the treatment failure as well as the reduced usefulness of older broad-spectrum antibiotics. Hence, a rather novel method has been in use to combat resistant pathogens since the last decade. To overcome this challenge, subtractive genomic analysis has been successfully carried out with the whole proteome of Brucella abortus strain 2308 using various bioinformatic tools and servers. Proteins nonhomologous to cattle and human were selected for metabolic analysis. Only three membrane proteins (ABC transporter permease, acriflavine resistance protein B, penicillin-binding protein 2) were found to be potential novel vaccine candidates with cattle as the host whereas one membrane protein (ABC transporter permease) was selected as novel drug target with human as the host. Development of novel vaccines and therapeutics through targeting inhibition of the functions of any of these essential proteins can lead to disruption of pathogen-specific metabolic pathways and thereby to the destruction and the eradication of this pathogen from respective hosts. The results of this study could facilitate the discovery and release of new and effective drugs and help in designing and producing potent vaccines against Brucella abortus strain 2308.

Keywords: Brucellosis; KEGG metabolic pathways; Subtractive genomics; Vaccine targets; Zoonotic disease.