title: Antibiotic tolerance in pneumococci.
abstract: When bacteria such as Staphylococcus aureus and Streptococcus pneumoniae are exposed to lytic antibiotics such as penicillin and vancomycin, a self-induced killing process is initiated in the organism. This killing occurs via both non-lytic and lytic processes. Recent data suggest that the non-lytic killing system, which might affect the cytoplasmic membrane, secondarily activates murein hydrolases that eventually lyse the cell. Disturbances in this suicide pathway can lead to antibiotic tolerance, a process whereby the antibiotic still exerts its bacteriostatic effects but the self-induced killing system is impaired. In mutants obtained in vitro, signaling pathways have been affected that show either increased or decreased antibiotic-induced killing. Among clinical isolates of S. pneumoniae that are tolerant to penicillin and/or vancomycin, we do not yet know whether these signaling pathways are affected. We could, however, demonstrate that the activity of murein hydrolases is negatively controlled by the production of capsular polysaccharides in one vancomycin-tolerant isolate. Hence, type and level of capsular expression might constitute one factor that determines the degree of lysis, once the killing signal has been elicited by the antibiotic.
authors.affiliation: Swedish Institute for Infectious Disease Control and Microbiology and Tumorbiology Center, Karolinska Institutet, Stockholm Sweden. birgitta.henriques@smiki.se
authors.forename: Benriques
authors.initials: B
authors.lastname: Henriques Normark
authors.forename: S
authors.initials: S
authors.lastname: Normark
mesh_terms: D000818:Animals; D000900:Anti-Bacterial Agents / Q000378:metabolism / Q000494:pharmacology*; D017209:Apoptosis; D001435:Bacteriophages / Q000378:metabolism; D024881:Drug Resistance, Bacterial / Q000502:physiology*; D006801:Humans; D007769:Lactams; D008956:Models, Chemical; D009238:N-Acetylmuramoyl-L-alanine Amidase / Q000502:physiology; D010406:Penicillins / Q000494:pharmacology; D010457:Peptidoglycan / Q000378:metabolism; D010957:Plasmids / Q000378:metabolism; D011817:Rabbits; D015398:Signal Transduction / Q000502:physiology; D013290:Streptococcal Infections / Q000188:drug therapy; D013296:Streptococcus pneumoniae / Q000187:drug effects* / Q000201:enzymology; D014640:Vancomycin / Q000494:pharmacology
chemical_list: D000900:Anti-Bacterial Agents; D007769:Lactams; D010406:Penicillins; D010457:Peptidoglycan; D014640:Vancomycin; D009238:N-Acetylmuramoyl-L-alanine Amidase