The effect of glutathione on type 1 fimbriation in Escherichia coli

A wide range of molecular studies are carried out on model organisms such as Escherichia coli. While most E. coli strains are commensal, some have evolved to produce toxins and other virulence factors and are pathogenic. Such a virulence factor are type 1 fimbriae, filamentous structures that are anchored in the outer membrane of the bacterial cell and enable the attachment of bacteria to host cells, as well as facilitating their invasion The production of type 1 fimbriae is regulated by phase variation. Inversion of fimS, a short DNA element that carries the promoter sequence for the fim gene operon, determines-" phase switching and requires the recombinases FimB and FimE. FimB catalyses OFF-to- ON switching, and levels of fimB expression regulate fimbrial production. The expression of fimB itself is regulated by many factors. This study demonstrates that the tripeptide glutathione is an activator offimB expression. Glutathione is likely to have a periplasmic site of action and is suggested to target and inactivate the periplasmic enzyme SReA. Since SpeA is the first enzyme in the polyamine biosynthetic pathway, levels of glutathione would determine levels of polyamines. It is proposed that polyamines inhibit fimB expression at both the transcriptional and post- transcriptional level, an optimal level of polyamines allowing maximum fimB expression. The regulation of fimB expression at the transcriptional level is potentially mediated via elevated levels of the regulatory protein H-NS, a known inhibitor of fimB expression. However, the polyamines may have a direct effect on fimB translation as well. Type 1 fimbriae are proinflammatory and a virulence factor in pathogenic E. coli. The level of reduced GSH in the periplasm may thus provide the bacterium with a key indicator of host defence activation. Moreover, the fact that both GSH and the polyamines protect against oxidative stress suggests a raison d'etre for their mutual regulation.