Final Report Summary - PGNFROMSHAPETOVIR (The role of peptidoglycan in bacterial cell physiology: from bacterial shape to host-microbe interactions) The bacterial cell wall is unique in its composition and role for bacteria. It fulfills an essential function in maintaining cell integrity giving shape to the cell. Because of its essential nature for bacteria, it is the target of existing antibiotics and still an excellent source for the discovery of new antibiotics. Its unique composition without equivalent in other kingdoms of life has made it as an excellent marker of bacterial origin and has been exploited by higher organisms to detect the presence of bacteria in their environment. We have been studying the metabolism of the bacterial cell wall component peptidoglycan using the bacterium Helicobacter pylori to better understand how the assembly of this structure gives rise to a particular cell shape. From this new knowledge, we have been developing novel therapeutic strategies to overcome the hurdle of antibiotic resistance. We have identified new Achilles heels in the machinery of assembly for which we have identified molecules able to interfere with this process. Besides the search for new antibiotics, we have been studying the role the bacterial cell wall plays in host-microbe interactions. We have uncovered that the detection by the host of this molecule of bacterial origin has beneficial effects on the host by priming the immune system to cope with the presence of a commensal flora in the gastrointestinal tract. Furthermore, we showed that during disease substructures of the peptidoglycan can help the immune system to restore balance back to normality. Finally, we have shown that many bacteria that are human pathogens have devised strategies to avoid host recognition of their peptidoglycan. These stealth mechanisms are part of the virulence strategy of these pathogens such as Helicobacter pylori, Listeria monocytogenes, Neisseria meningitidis, Yersina pestis, Bacillus anthracis among others.
