Increased protein secretion and adherence to HeLa cells by Shigella spp. following growth in the presence of bile salts

Abstract

Growth of Shigella spp. in the presence of the bile salt deoxycholate or chenodeoxycholate enhanced the bacterial invasion of HeLa cells. Growth in the presence of other structurally similar bile salts or detergents had little or no effect. Deoxycholate-enhanced invasion was not observed when bacteria were exposed to deoxycholate at low temperatures or when chloramphenicol was added to the growth medium, indicating that bacterial growth and protein synthesis are required. Increased invasion is associated with the presence of an intact Shigella virulence plasmid and is correlated with increased secretion of a set of proteins, including the Ipa proteins, to the outer membrane and into the growth medium. The increased invasion induced by the bile salts appears to be due to increased adherence. The enhanced adherence was specific to Shigella spp., since the enteroinvasive Escherichia coli strains tested did not exhibit the effect in response to growth in bile salts.

The interaction between bacteria and bile

“…Contrary to the negative effects of bile on Salmonella invasion, Pope et al [244] showed that growth of Shigella spp. (S. flexneri and S. dysenteriae) in bile salts (deoxycholate or chenodeoxycholate) results in an increase in Ipa protein secretion and increased invasion of epithelial cells due to enhanced adherence.…”

Transcriptional regulation ofSalmonella entericaserovar Typhimurium genes by bile

“…Bile has been demonstrated in both bacteria and parasites to regulate genes for bile resistance, as well as genes within pathways important for virulence [4][5][6][7][8][9][10]. Bile salt hydrolase (BSH) is a protein found in most gastrointestinal commensals, but not enteropathogens, allowing for continued survival within the host [11].…”

“…Gene regulation by bile has also been observed in the gastrointestinal parasite, Giardia lamblia, in which bile can be used as a metabolic substrate and plays a role in promoting encystation, which is critical for pathogenesis [9]. Shigella flexneri grown in the presence of bile exhibits increased protein secretion and enhanced invasion of epithelial cells [5]. In Vibrio cholerae, bile enhances motility, while simultaneously repressing expression of other virulence factors, such as toxin co-regulated pilus and cholera toxin [4].…”

Hemagglutinating Factor (HAF) Associated with Adhesiveness in Enteroinvasive Escherichia coli (EIEC)

“…Adherence and invasion of epithelial cells has been studied extensively in vitro by infecting cell lines such as HeLa cells with strains of EIEC (14,16,20). Based on these bibliography HeLa cells were chosen for development of the assays.…”