title: The pneumococcal cell envelope stress-sensing system LiaFSR is activated by murein hydrolases and lipid II-interacting antibiotics.
abstract: In the Firmicutes, two-component regulatory systems of the LiaSR type sense and orchestrate the response to various agents that perturb cell envelope functions, in particular lipid II cycle inhibitors. In the current study, we found that the corresponding system in Streptococcus pneumoniae displays similar properties but, in addition, responds to cell envelope stress elicited by murein hydrolases. During competence for genetic transformation, pneumococci attack and lyse noncompetent siblings present in the same environment. This phenomenon, termed fratricide, increases the efficiency of horizontal gene transfer in vitro and is believed to stimulate gene exchange also under natural conditions. Lysis of noncompetent target cells is mediated by the putative murein hydrolase CbpD, the key effector of the fratricide mechanism, and the autolysins LytA and LytC. To avoid succumbing to their own lysins, competent attacker cells must possess a protective mechanism rendering them immune. The most important component of this mechanism is ComM, an integral membrane protein of unknown function that is expressed only in competent cells. Here, we show that a second layer of self-protection is provided by the pneumococcal LiaFSR system, which senses the damage inflicted to the cell wall by CbpD, LytA, and LytC. Two members of the LiaFSR regulon, spr0810 and PcpC (spr0351), were shown to contribute to the LiaFSR-coordinated protection against fratricide-induced self-lysis.
authors.affiliation: Department of Chemistry, Biotechnology, and Food Science, Norwegian University of Life Sciences, As, Norway.
authors.forename: Vegard
authors.initials: V
authors.lastname: Eldholm
authors.forename: Beatrice
authors.initials: B
authors.lastname: Gutt
authors.forename: Ola
authors.initials: O
authors.lastname: Johnsborg
authors.forename: Reinhold
authors.initials: R
authors.lastname: Brückner
authors.forename: Patrick
authors.initials: P
authors.lastname: Maurer
authors.forename: Regine
authors.initials: R
authors.lastname: Hakenbeck
authors.forename: Thorsten
authors.initials: T
authors.lastname: Mascher
authors.forename: Leiv Sigve
authors.initials: LS
authors.lastname: Håvarstein
mesh_terms: D000595:Amino Acid Sequence; D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D001426:Bacterial Proteins / Q000378:metabolism*; D001433:Bacteriolysis; D001483:Base Sequence; D005798:Genes, Bacterial; D008969:Molecular Sequence Data; D009238:N-Acetylmuramoyl-L-alanine Amidase / Q000378:metabolism*; D018085:Regulon; D016415:Sequence Alignment; D015398:Signal Transduction; D013296:Streptococcus pneumoniae / Q000187:drug effects* / Q000502:physiology; D013312:Stress, Physiological; D014538:Uridine Diphosphate N-Acetylmuramic Acid / Q000031:analogs & derivatives* / Q000378:metabolism
chemical_list: D000900:Anti-Bacterial Agents; D001426:Bacterial Proteins; D014538:Uridine Diphosphate N-Acetylmuramic Acid; C069249:muramyl-NAc-(pentapeptide)pyrophosphoryl-undecaprenol; D009238:N-Acetylmuramoyl-L-alanine Amidase