Snapshots of a molecular chameleon
H. pylori has been associated with humankind since ancient migrations and is today still present in about halve of the world population. The bacterium has a fast evolving genome and is constantly adapting to changing conditions in its host. Kristof Moonens and coworkers now report in Cell Host & Microbe how the high sequence variation in the blood group antigen binding adhesin BabA leads to the functional polymorphism in its binding characteristics.
Kristof Moonens (VIB/VUB): ‘By determining the X-ray structures of different BabA proteins, we could establish a general framework for ABO blood group binding by the adhesin. Thomas Borén’s group had previously shown that “specialist” H. pylori strains only bind to gastric tissue of blood group O individuals, whereas “generalist” strains interact with all types of blood group individuals. Now we can show that a select network of residues in the protein steer the differences in binding preferences.’
Perspectives for H. pylori eradication therapy
Resistance of bacterial pathogens to antibiotics is becoming a widespread problem, and H. pylori proofs not different. Today, H. pylori eradication therapy already needs sustained treatment with a cocktail of 2-3 antibiotics. The quest for new treatment options or a vaccine is on, in particular in regions where H. pylori infections lead to a gastric cancer and ulcer epidemic. The new study provides perspectives to develop drugs that disrupt the bacterium’s ability to hold on to the stomach mucosa.
Thomas Borén (Umeå University, Sweden): ‘We could show that treatment with the redoxactive pharmaceutic N-acetylcysteine annihilates BabA function and furthermore that N-acetylcysteine lowers gastric mucosal neutrophil infiltration, i.e. stomach inflammation, in H. pylori-infected mice, providing perspectives on possible H. pylori eradication therapies. The additive effect of N-acetylcysteine on antibiotic eradication therapies has previously been reported in literature and now we have found a molecular basis and explanation for this effect.’
Han Remaut (VIB/VUB): ‘Amidst BabA’s receptor binding site that is constantly changing lies a conserved anchor point, a short disulfide-bound loop that embraces a fucose residue in the ABO blood group sugars. This newly elucidated structural element is inactivated by reduction and forms the basis for the rational design of novel anti-adhesive drugs that would reduce bacterial attachment, stomach inflammation and hence lower the risk for overt disease development.’
