Applications of Genomics Derived Characteristics for Evolutionary and Functional studies and for Development of Novel Diagnostics and Therapeutics

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Microorganisms play vital roles in all aspects of life including recycling of organic materials, nitrogen fixation, photosynthesis, waste decomposition, bioremediation, production of antibiotics and other important compounds, as well as major determinants of human health and diseases. In view of their central roles in health care, agriculture, mining, fishing and other areas, it is important to develop reliable means for distinguishing different groups of microorganisms. However, most of the bacterial groups are currently distinguished from each other only on the basis of their branching in the 16S rRNA trees. As 16S sequence information does not, in itself, provide prediction of phenotypic trait(s) for most groups, no group-specific molecular or biochemical properties are known. For a reliable and comprehensive understanding of the biological properties of diverse groups of microorganisms, it is critically important to identify evolutionarily conserved traits that are uniquely shared by specific groups of interest and which can distinguish them from all others. Genome sequences provide a unique and definitive resource for discovering novel molecular markers that are specific for each group. Using genome sequences, my group has pioneered the discovery of two types of molecular markers, Conserved Signature Indels (CSIs) and Conserved Signature Proteins (CSPs), which are uniquely found in specific groups of organisms. As the genotype specifies phenotype, these molecular markers will provide important means for discovering novel biochemical/biological properties uniquely shared by each group of organisms and for development of novel diagnostics and therapeutics aimed at these organisms. During the next 5 years, our work in this area will use genome sequences to comprehensively investigate three important groups of bacteria viz. Pseudomonadales, Lactobacillales and Bacillales. These groups harbor many “priority human pathogens,” several major plant pathogens, as well as other bacteria playing key roles in the dairy and agriculture industries. We will identify multiple reliable characteristics specific for different disease-causing as well as beneficial bacteria that are part of these large groups, thereby providing important means for discovering novel biochemical traits of these bacteria and improving the means for their identification. Additionally, an important objective of this proposal is to test/establish the proof of principle that the CSIs in protein structures can be targeted for development of novel cell-growth inhibitory compounds. The establishment of this concept can provide a vast resource of new classes of drugs/inhibitors targeting the CSI-containing organisms. Overall, the work proposed here should greatly advance our understanding of a number of important groups of microorganisms and the applications of these findings should lead to a significant reduction in the health, agricultural and economic burden caused by these bacteria.