In Vitro Antibacterial Activity of Unconjugated and Conjugated Bile Salts on Staphylococcus aureus

Abstract

Bile salts are potent antimicrobial agents and are an important component of innate defenses in the intestine, giving protection against invasive organisms. They play an important role in determining microbial ecology of the intestine and alterations in their levels can lead to increased colonization by pathogens. We have previously demonstrated survival of the opportunistic pathogen Staphylococcus aureus in the human colonic model. Thus investigating the interaction between S. aureus and bile salts is an important factor in understanding its ability to colonize in the host intestine. Harnessing bile salts may also give a new avenue to explore in the development of therapeutic strategies to control drug resistant bacteria. Despite this importance, the antibacterial activity of bile salts on S. aureus is poorly understood. In this study, we investigated the antibacterial effects of the major unconjugated and conjugated bile salts on S. aureus. Several concentration-dependent antibacterial mechanisms were found. Unconjugated bile salts at their minimum inhibitory concentration (cholic and deoxycholic acid at 20 and 1 mM, respectively) killed S. aureus, and this was associated with increased membrane disruption and leakage of cellular contents. Unconjugated bile salts (cholic and deoxycholic acid at 8 and 0.4 mM, respectively) and conjugated bile salts (glycocholic and taurocholic acid at 20 mM) at their sub inhibitory concentrations were still able to inhibit growth through disruption of the proton motive force and increased membrane permeability. We also demonstrated that unconjugated bile salts possess more potent antibacterial action on S. aureus than conjugated bile salts.

Inactivation of the bacterial pathogens Staphylococcus pseudintermedius and Acinetobacter baumannii by butanoic acid

“…Sannasiddappa et al . () also observed a similar morphological change after exposure of S. aureus to bile salts. These analyses were determined at a higher magnification and thus the possibility that butanoic acid induces a similar response in A. baumannii and S. pseudintermedius cannot be discounted.…”

Synergistic Therapies as a Promising Option for the Treatment of Antibiotic-Resistant Helicobacter pylori

“…Bile is a type of secretion produced naturally by mammals and other vertebrates ( Table 1 ) [ 82 , 83 , 84 , 85 , 86 , 87 , 88 ]. This fluid is rich in bile acids, which are aliphatic molecules that are conjugated in the liver with taurine or glycine.…”

Emerging roles of bile acids in mucosal immunity and inflammation

“…[65][66][67] However, the potent antimicrobial activity of BAs observed in vivo is not evident at physiological concentrations in vitro. 33,[68][69][70][71] Therefore, two additional mechanisms have been proposed to explain the antimicrobial activities of BAs in vivo. First, BAs present in bile fluid in vivo exist as mixed micelles, together with phospholipids, long-chain fatty acids, and bilirubin; the bacteriostatic functions of BAs are enhanced in the presence of other bile constituents, particularly long-chain fatty acids.…”