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Identification and Characterization of Potential Drug Targets in Brucella Melitensis

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Why is it important?

David Bruce identified the bacterium Brucella in the year 1887 and in the year 1918, Alice Evans, an American Microbiologist suggested the term “Brucellosis” to honor David Bruce. Brucellosis is characterized by protean of manifestations targeting vital organs, organ systems and interfere with the organism biological framework. This aspect attracted the attention of a correspondingly multidisciplinary forum of biomedical practitioners and researchers working in the area of microbiology, biochemistry and biotechnology. Brucellosis is caused by small aerobic gram-negative coccobacilli, Brucella, which is a non-encapsulated, non-motile, non-spore forming facultative intracellular bacterium. Brucellosis is one of the cogent examples of zoonotic bacterial diseases which is transmitted from infected animal reservoirs to humans through various routes including consumption of infected animal milk or milk products, infected animal parts, ruptures of skin, mucous membranes and by inhalation of infected aerosolize particles. The symptoms associated with brucellosis are fever, fatigue, malaise, anorexia, chills, sweats, headache, backache, myalgia, arthralgia, weight loss and may affect the organs, central nervous system. At present, the genus Brucella comprises of six species that infect a wide range of animals Brucella abortus, Brucella melitensis, Brucella suis, Brucella canis, Brucella neotomae, Brucella ovis and among the six species, except the last two species of Brucella, B. neotomae, and B. ovis are known to infect the humans. B. melitensis is highly virulent form of Brucella and acts as an agent of biological warfare and thus, an organism highlighted for bioterrorism. The epidemiological studies have shown that the Brucella militensis is complex and change from time to time and the available vaccines so far are effective against animals but not for humans due to its pathogenic nature. Thus, there is a need for the development of vaccines against human brucellosis. The current chapter provides comprehensive details about the genome architecture, pathogenesis, host-interactions and the underlying mechanisms in animals and humans of B. militensis. The present chapter also highlights the applications of computational tools and their applicability in the identification of drug targets in B. militensis 16M.

Perspectives

The role of computational strategies, i.e., blending of chemoinformatics and biology in drug discovery, is well appreciated; especially, this is true in case of handling harmful pathogens. Nowadays, the identification of potential drug targets is one of the critical factors for effective therapy against pathogen-mediated diseases including the biowar pathogens like Anthrax, Clostridium, Brucella, etc. To accomplish this task, it is important to consider two aspects: 1) health risks associated with direct handling of biowar pathogens and 2) economic aspects towards the identification of drug targets using in vivo experiments. Therefore, to overcome these aspects, alternative strategies are immediately needed. One of the computational strategies associated with the drug discovery against harmful pathogens is subtractive genomics. This approach depends on two key elements: knowledge about the complete microbial genome sequences of pathogenic bacteria and the human genome. Subtractive genomic approach acts as a platform to effectively screen the human diseases by utilizing complete genome sequences of pathogens for distinct pathological pathways and novel virulence factors.

Dr., Pradeepkiran Jangampalli Adi
Texas Tech University System

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This page is a summary of: Introduction to brucellosis, January 2021, Elsevier,
DOI: 10.1016/b978-0-323-85681-2.00007-0.
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