title: Overexpression of the fratricide immunity protein ComM leads to growth inhibition and morphological abnormalities in Streptococcus pneumoniae.
abstract: The important human pathogen Streptococcus pneumoniae is a naturally transformable species. When developing the competent state, it expresses proteins involved in DNA uptake, DNA processing and homologous recombination. In addition to the proteins required for the transformation process, competent pneumococci express proteins involved in a predatory DNA acquisition mechanism termed fratricide. This is a mechanism by which the competent pneumococci secrete a muralytic fratricin termed CbpD, which lyses susceptible sister cells or closely related streptococcal species. The released DNA can then be taken up by the competent pneumococci and integrated into their genomes. To avoid committing suicide, competent pneumococci produce an integral membrane protein, ComM, which protects them against CbpD by an unknown mechanism. In the present study, we show that overexpression of ComM results in growth inhibition and development of severe morphological abnormalities, such as cell elongation, misplacement of the septum and inhibition of septal cross-wall synthesis. The toxic effect of ComM is tolerated during competence because it is not allowed to accumulate in the competent cells. We provide evidence that an intra-membrane protease called RseP is involved in the process of controlling the ComM levels, since △rseP mutants produce higher amounts of ComM compared to wild-type cells. The data presented here indicate that ComM mediates immunity against CbpD by a mechanism that is detrimental to the pneumococcus if exaggerated.
authors.affiliation: Department of Chemistry, Biotechnology and Food Science, Norwegian University of Life Sciences, NO-1432 Ås, Norway.
authors.forename: Daniel
authors.initials: D
authors.lastname: Straume
authors.affiliation: Department of Chemistry, Biotechnology and Food Science, Norwegian University of Life Sciences, NO-1432 Ås, Norway.
authors.forename: Gro Anita
authors.initials: GA
authors.lastname: Stamsås
authors.affiliation: Department of Chemistry, Biotechnology and Food Science, Norwegian University of Life Sciences, NO-1432 Ås, Norway.
authors.forename: Zhian
authors.initials: Z
authors.lastname: Salehian
authors.affiliation: Department of Chemistry, Biotechnology and Food Science, Norwegian University of Life Sciences, NO-1432 Ås, Norway.
authors.forename: Leiv Sigve
authors.initials: LS
authors.lastname: Håvarstein
mesh_terms: D000581:Amidohydrolases / Q000235:genetics / Q000378:metabolism*; D001426:Bacterial Proteins / Q000096:biosynthesis* / Q000235:genetics / Q000378:metabolism; D001433:Bacteriolysis / Q000502:physiology*; D002473:Cell Wall / Q000378:metabolism; D061269:DNA Transformation Competence / Q000235:genetics*; D004269:DNA, Bacterial / Q000235:genetics; D008565:Membrane Proteins / Q000096:biosynthesis* / Q000235:genetics / Q000378:metabolism; D010447:Peptide Hydrolases / Q000235:genetics / Q000378:metabolism*; D010457:Peptidoglycan / Q000096:biosynthesis; D013296:Streptococcus pneumoniae / Q000235:genetics / Q000254:growth & development* / Q000472:pathogenicity; D014169:Transformation, Bacterial / Q000235:genetics; D037521:Virulence Factors / Q000235:genetics / Q000378:metabolism
chemical_list: D001426:Bacterial Proteins; D004269:DNA, Bacterial; D008565:Membrane Proteins; D010457:Peptidoglycan; D037521:Virulence Factors; D010447:Peptide Hydrolases; D000581:Amidohydrolases; C569012:CbpD protein, Streptococcus pneumoniae