Molecular analysis of antibiotic tolerance in pneumococci

Widespread pneumococcal resistance and the emergence of tolerance underscores the need to develop new antimicrobials. Uncovering the mechanisms of autolysin activation could yield not only new antibacterial targets but also ways to eradicate a pool of bacteria facilitating the spread of resistance. Although several genes contributing to antibiotic tolerance among pneumococci have been identified, those important in the clinical arena thus far are in a single gene cluster, vex/pep27/vncS/vncR. Mutations within this signal transduction system represent at least one mechanism, which explains tolerance to both penicillin and vancomycin. Since mutations in this locus do not result in tolerance to penicillin alone, there must be other, yet unknown, mutations which account for tolerance to a single antibiotic. In the case of pneumococci, there exist two more autolysins other than LytA suggesting our understanding of how bacteria die is currently only at the beginning.