Long-chain fatty acids (LCFAs) are a rich source of metabolic energy, an essential component of membranes, and important effector molecules that regulate myriad cellular processes. As energy-rich nutrients, the role of host-derived LCFAs in supporting bacterial survival and infectivity is well appreciated. However, LCFA degradation generates a large number of reduced cofactors, and thus its use is expected to confer redox stress in bacteria. LCFA metabolism has been studied in great detail, especially in E. coli, where the earliest studies date back to the 1960s, but the interconnection of LCFA degradation with other cellular processes remained largely unknown. In the last few years, our work in a laboratory strain of E. coli has shown that LCFA degradation induces oxidative stress and also impedes oxidative protein folding. However, bacteria induce sophisticated cellular responses to maintain redox homeostasis. We are now interested in understanding the mechanism of activation of defense players during LCFA metabolism and the likely feedback imparted by them. The use of LCFAs by pathogens makes it imperative to understand whether they are also predisposed to redox stress and, if so, what are their combat strategies. We have thus initiated investigating these issues in pathogenic bacteria as well. We believe that our work on addressing how LCFA metabolism is integrated with stress responses will pave the way for understanding the impact of this interconnection on host-bacterial interactions.

Sugar acids, the oxidized derivatives of sugars, are used as carbon and energy source by several bacteria. Genome-scale studies in the last couple of decades have emphasized the importance of the metabolism of a sugar acid, D-galactonate, in the interaction of enteric bacteria with their host. The genes involved in D-galactonate metabolism are regulated positively by the cyclic AMP receptor protein-cyclic AMP (cAMP-CRP) complex and negatively by the transcriptional repressor, DgoR. Using a combination of genetic, biochemical, and bioinformatics approaches, we have established E. coli DgoR as a GntR/FadR family transcriptional regulator and identified the promoter, operator, effector, and effector-binding cavity of DgoR. Further, our work suggests that D-galactonate metabolism is under complex regulation; it is regulated by players besides cAMP-CRP and DgoR. We are interested in investigating the interplay between these regulatory components in governing D-galactonate metabolism and understanding their physiological relevance. Dysregulation of carbon metabolism brought about by changes in regulatory elements can dramatically influence bacterial physiology. We are thus interested in investigating how variations in the components involved in regulating D-galactonate metabolism impact colonization of enteric bacteria inside their host.