Pseudomonas aeruginosa

Pseudomonas aeruginosa continues to develop antibiotic resistance, remaining potentially fatal to patients with cystic fibrosis. It appears to escape host defences by activating the GTPase activity of small G proteins that are involved in rearranging the cytoskeleton. However, researchers in Germany have revealed the structure of the N-terminal domain of the exotoxin responsible, exotoxin S (ExoS-N), hopefully providing clues for new drugs that could attenuate the bacteria (Nat Struct Biol 2001 8;23-26).

Dr Alfred Wittinghofer et al of the Max-Planck-Institut für Molekulare Physiologie in Dortmund, Germany, found that the GAP domain of ExoS is an all-helical protein, and that its interactions with Rac, a human G protein, are different from those of other GTPase-activating proteins in the host cell. Disruption of the gene encoding ExoS significantly reduces the virulence of the bacteria. Knowing the structure of ExoS-N should make it possible to find drugs to block its function.