Structural Aspects of Helicobacter pylori Antibiotic Resistance.

ABSTRACT

Resistance to antibiotics of Helicobacter pylori infections is growing rapidly together with the need for more potent antimicrobials or novel strategies to recover the efficacy of the existing ones. Despite the main mechanisms according to which H. pylori acquires resistance are common to other microbial infections affecting humans, H. pylori has its own peculiarities, mostly due to the unique conditions experienced by the bacterium in the gastric niche. Possibly the most used of the antibiotics for H. pylori are those molecules that bind to the ribosome or to the DNA and RNA machinery, and in doing so they interfere with protein synthesis. Another important class is represented by molecules that binds to some enzyme essential for the bacterium survival, as in the case of enzymes involved in the bacterial wall biosynthesis. The mechanism used by the bacterium to fight antibiotics can be grouped in three classes (i) mutations of some key residues in the protein that binds the inhibitor, (ii) regulation of the efflux systems or of the membrane permeability in order to reduce the uptake of the antibiotic, and (iii) other more complex indirect effects. Interestingly, the production of enzymes that degrade the antibiotics (as in the case of ß-lactamases in many other bacteria) has not been clearly detected in H. pylori. The structural aspects of resistance players have not been object of extensive studies yet and the structure of very few H. pylori proteins involved in the resistance mechanisms are determined till now. Models of the proteins that play key roles in reducing antimicrobials susceptibility and their implications will be discussed in this chapter.