Of Bacteria and Bile

The antibacterial activities of bile salts include detergent activity on cell membranes, protein denaturation, and DNA damage. However, many bacterial species are resistant to the antibacterial activity of bile salts. Bile salts may thus be viewed both as antibacterial compounds and as signals used by bacteria to identify bile-containing animal environments. This chapter reviews the mechanisms employed by Escherichia coli, Salmonella enterica, and other intestinal bacteria to respond to bile salts, with emphasis on their relevance for pathogenesis. The reader is also referred to two comprehensive, insightful reviews on bacterial responses to bile. Unconjugated forms of bile salts are amphipatic molecules that can enter the bacterial cell by crossing membrane bilayers. Furthermore, in the outer membrane of gram-negative bacteria, porins provide passage to both unconjugated and conjugated bile salts. Bile salts, especially if unconjugated, may easily reach the bacterial ctyoplasm by diffusion. Bile salts may also bind to specific receptors in the bacterial surface, activating signal transduction pathways that change gene expression patterns. Bile extract or individual bile salts can be added to microbiological media, thus permitting reductionist studies of bacterial bile resistance in the laboratory. It is hypothesized that nonmutational, reversible resistance may involve stochastic activation of one or more efflux systems that transport bile outside the cell.