Survival of the Fittest: How Bacterial Pathogens Utilize Bile To Enhance Infection

Abstract

SUMMARYBacterial pathogens have coevolved with humans in order to efficiently infect, replicate within, and be transmitted to new hosts to ensure survival and a continual infection cycle. For enteric pathogens, the ability to adapt to numerous host factors under the harsh conditions of the gastrointestinal tract is critical for establishing infection. One such host factor readily encountered by enteric bacteria is bile, an innately antimicrobial detergent-like compound essential for digestion and nutrient absorption. Not only have enteric pathogens evolved to resist the bactericidal conditions of bile, but these bacteria also utilize bile as a signal to enhance virulence regulation for efficient infection. This review provides a comprehensive and up-to-date analysis of bile-related research with enteric pathogens. From common responses to the unique expression of specific virulence factors, each pathogen has overcome significant challenges to establish infection in the gastrointestinal tract. Utilization of bile as a signal to modulate virulence factor expression has led to important insights for our understanding of virulence mechanisms for many pathogens. Further research on enteric pathogens exposed to thisin vivosignal will benefit therapeutic and vaccine development and ultimately enhance our success at combating such elite pathogens.

Analysis of Shigella flexneri Resistance, Biofilm Formation, and Transcriptional Profile in Response to Bile Salts

“…Bile also solubilizes lipid-based microbial membranes to function as an endogenous antimicrobial compound (9). Many enteric pathogens have developed multiple strategies to resist the bactericidal effects of bile while also utilizing this host signal to regulate virulence factor expression (11). For the first time, this work identifies bile salt resistance strategies used by Shigella that we hypothesize are required to successfully transit the small intestine prior to infection in the colon.…”

“…efflux pumps (11,(27)(28)(29)(30)(31)(32)(33)(34). Efflux pumps are utilized by bacteria to expel antibiotics and other harmful substances from the bacterial cytosol.…”

“…In the small intestine, concentrations of bile salts range from 0.2% to 2% (wt/vol) depending on time of day, diet, and the individual (8). Bile is bactericidal (9,10); however, Gram-negative bacteria, particularly enteric pathogens, are known to resist the bactericidal activity of bile and utilize this host component as a localization signal to regulate virulence gene expression and enhance infection (11).…”

Lack of the PGA exopolysaccharide in Salmonella as an adaptive trait for survival in the host

“…During systemic infection, Salmonella is able to transit from the liver into the gallbladder, where it can either induce inflammation and acute infection or persist chronically, creating a carrier state [74–76]. Several cell components and mechanisms have been related with Salmonella resistance to bile [77,78]. On one hand, different efflux pumps transport bile salts outside the cell decreasing their intracellular concentration [79,80].…”

“…Bile salts are maintained at high concentrations in the duodenum, jejunum, and proximal ileum. In the distal ileum, bile salts are absorbed into the blood-stream, and the majority of bile is recycled back into the small intestine and does not enter the colon [78]. E .…”