Clinicians had assumed that E. coli and other bacteria that cause UTIs were not invading cells of the urinary tract, but in June 2003, Hultgren's lab produced images of E. coli forming biofilms inside bladder cells. Biofilms are networks of single-celled pathogens that cooperate with each other to form structures that are resistant to attack.
"Once these bacteria begin to replicate inside their target cell, they almost behave more like a multicellular organism," Hultgren explains. "Some kind of switch occurs, probably due to processing of environmental cues, and instead of acting like individual bacteria, they behave more in a multicellular manner, working together to defeat the cell's defenses."
Hultgren and his coauthors divided E. coli's infectious process into four stages. In the first, bacteria enter bladder cells and begin replicating rapidly. In the second stage, they decrease their size and replication rate and begin to form the intracellular bacterial community (IBC), a podlike structure that Hultgren compared to a marble in a balloon.
In the third stage, bacteria begin to break out of the IBC and swim away.
"It's like peeling an onion," says Sheryl S. Justice, Ph.D., a postdoctoral fellow in Hultgren's lab and one of three lead authors of the paper. "They come off the outside of the IBC in successive layers."
During the fourth stage, some of the bacteria from the dispersed IBC become filaments, taking on long, thin, needle-like shapes. The new shapes may help them evade the immune system and seek chances to start new infections both in the urinary tract of their hosts and in new hosts.
The movies also reveal that groups of E. coli will sometimes shift into an inactive or quiescent state.