Potential Inhibition of Lactate Dehydrogenase by Oxamate in Enterococcus faecalis

Abstract

E. faecalis is an ancient bacteria responsible for a lot of nosocomial infections in human beings. One of the main reasons for its survival over millions of years is its resistance to various physiological stresses and also to antibiotic drugs used for its treatment. The acquired antibiotic resistance in the bacteria is major concern of the modern medicine. E. faecalis depends majorly on the enzyme Lactate Dehydrogenase (LDH) which maintains redox balance for growth, resistance and its virulence. Oxamate, the salt of oxamic acid, is a compound with a similar structure to pyruvate and is used as an anticancer agent worldwide that can competitively bind to LDH and inhibit its activity. Further evidence of oxamate’s binding with LDH is also provided by computational approaches. In this study we attempted to evaluate the antibacterial effect of oxamate on E. faecalis by inhibiting LDH enzyme. We found out the minimum inhibitory concentration of oxamate after adding its different concentrations (ug/mL) to the bacterial culture and running it on the 96-well plate on the microplate reader. Maximum growth inhibition was shown in higher doses of inhibitor (100, 150, 200 ug/mL) while little to no inhibition was shown on smaller doses (5, 10, 25, 50, 75 ug/mL). We employed six different stressors, SDS, H2O2, Ethanol, DMSO, Glucose and HOCl, in addition to the minimum inhibitory concentration of oxamate. A moderate level of inhibition was shown in the the cultures containing MIC of oxamate with SDS and Glucose, while little to no inhibition was shown in the cultures contaning oxamate with DMSO and H2O2. A significant amount of inhibition was shown in the culture containing the inhibitor with Ethanol. With everything into account, it was seen that activity of LDH was inhibited strikingly by oxamate.