Identification of icsA, a plasmid locus of Shigella flexneri that governs bacterial intra- and intercellular spread through interaction with F-actin.

TLDR

Shigella spreads within infected epithelial cells and to adjacent cells by exploiting host cell F‑actin, a process essential for infection foci and mucosal abscess formation, as shown by cytochalasin‑D inhibition and phallacidin labeling. The icsA locus on plasmid pWR100 encodes a 120‑kDa outer‑membrane protein that mediates interaction with host microfilaments, driving intra‑ and intercellular movement. These movements generate extracellular protrusions that facilitate cell‑to‑cell spread.

Abstract

The capacity of Shigella to spread within the cytosol of infected epithelial cells and to infect adjacent cells is critical for the development of infection foci, which lead to mucosal abscesses. Shigella is a nonmotile microorganism that appears to utilize host cell microfilaments to generate intra- as well as intercellular movements, since this movement was inhibited by cytochalasin D and involvement of F-actin was demonstrated by direct labeling of infected cells with the specific dye N-(7-nitrobenz-2-oxa-1,3-diazol-4-yl)phallacidin. Such movements led to the formation of extracellular protrusions, which may explain cell to cell spread. icsA, a locus necessary for intra- and intercellular spread, was identified on the Shigella flexneri virulence plasmid pWR100. This locus was cloned and shown to express a 120-kDa outer membrane protein, which plays an important role in the interactions established between host cell microfilaments and the bacterial surface, thus leading to intracellular movement.