A microcalorimetric method to determine antimicrobial effects of two bile acid derivatives on Staphylococcus aureus.

Using microcalorimetry, the characteristic metabolic heat flow power-time curves of S. aureus growth affected by Ursodesoxycholic acid and Hyodeoxycholic acid were measured at 37 °C. The thermal-kinetic parameters such as, growth rate constant k, the maximum power output ( P), the time corresponding to the maximum power output ( t), total heat-production Q, half inhibitory concentration of the drugs ( IC) were calculated from the growth curves. For both HDCA and UDCA, with the increasing of concentration, k, P, and Q decreased, meanwhile, k- c fit a linear equation, t was prolonged correspondingly. Principle component analysis, the results indicated t might be the main parameter in evaluating the antibacterial activity of HDCA and UDCA in microcalorimetric method. Combining with t and IC, the results revealed that the differences and trends of antibacterial activity of these bile acid derivatives were: HDCA > UDCA. Structure-activity relationship (SAR) analysis showed that the α-OH at C-3 and C-6 position at equal pace on the steroid nucleus enhanced the hydrophilicity of HDCA, which led to a stronger antibacterial effect than UDCA. In this study, a useful tool was provided to accurately evaluate the antibacterial effects of bile acid derivatives. The thermolysis curve recorded by microcalorimetry could provide a lot of kinetic and thermodynamic information for the study of growth process of living microbial, which could be helpful in the screening of high efficacy antibacterial agents. [ABSTRACT FROM AUTHOR]