Selection for phage resistance reduces virulence of Shigella flexneri

There is increasing interest in phage therapy as an alternative to chemical antibiotics for treating bacterial infections, especially using phages that select for evolutionary trade-offs between increased phage resistance and decreased fitness traits such as virulence in target bacteria. A vast repertoire of virulence factors allows the opportunistic bacterial pathogen, Shigella flexneri, to invade human gut epithelial cells, to replicate intracellularly, and to evade host immunity through intercellular spread; the latter is an infection stage that causes tissue damage, contributing to host mortality. It is previously shown that outer membrane porin OmpA of S. flexneri is necessary for polar localization of virulence factor IcsA, which polymerizes host actin and results in bacterial motility within infected cells. We hypothesized that a phage which uses OmpA as a receptor to recognize, bind and infect S. flexneri, should select for phage-resistant mutants with attenuated intercellular s...