Identifying feasible metabolic routes in Mycobacterium smegmatis and possible alterations under diverse nutrient conditions

Background: Many studies on M. tuberculosis have emerged from using M. smegmatis MC(2)155 (Msm), since they share significant similarities and yet Msm is non-pathogenic and faster growing. Although several individual molecules have been studied from Msm, many questions remain open about its metabolism as a whole and its capability to be versatile. Adaptability and versatility are emergent properties of a system, warranting a molecular systems perspective to understand them. Results: We identify feasible metabolic pathways in Msm in reference condition with transcriptome, phenotypic microarray, along with functional annotation of the genome. Together with transcriptome data, specific genes from a set of alternatives have been mapped onto different pathways. About 257 metabolic pathways can be considered to be feasible in Msm. Next, we probe cellular metabolism with an array of alternative carbon and nitrogen sources and identify those that are utilized and favour growth as well as those that do not support growth. In all, about 135 points in the entire metabolic map are probed. Analyzing growth patterns under these conditions, lead us to hypothesize different pathways that can become active in various conditions and possible alternate routes that may be induced, thus explaining the observed physiological adaptations. Conclusions: The study provides the first detailed analysis of feasible pathways towards adaptability. We obtain mechanistic insights that explain observed phenotypic behaviour by studying gene-expression profiles and pathways inferred from the genome sequence. Comparison of transcriptome and phenome analysis of Msm and Mtb provides a rationale for understanding commonalities in metabolic adaptability.