Your browser doesn't support javascript.
loading
A novel peptidoglycan binding protein crucial for PBP1A-mediated cell wall biogenesis in Vibrio cholerae.
Dörr, Tobias; Lam, Hubert; Alvarez, Laura; Cava, Felipe; Davis, Brigid M; Waldor, Matthew K.
Afiliación
  • Dörr T; Division of Infectious Diseases, Brigham & Women's Hospital and Department of Microbiology and Immunobiology, Harvard Medical School, Boston, Massachusetts, United States of America; Howard Hughes Medical Institute, Chevy Chase, Maryland, United States of America.
  • Lam H; Division of Infectious Diseases, Brigham & Women's Hospital and Department of Microbiology and Immunobiology, Harvard Medical School, Boston, Massachusetts, United States of America.
  • Alvarez L; Laboratory for Molecular Infection Medicine Sweden, Department of Molecular Biology, Umeå University, Umeå, Sweden.
  • Cava F; Laboratory for Molecular Infection Medicine Sweden, Department of Molecular Biology, Umeå University, Umeå, Sweden.
  • Davis BM; Division of Infectious Diseases, Brigham & Women's Hospital and Department of Microbiology and Immunobiology, Harvard Medical School, Boston, Massachusetts, United States of America; Howard Hughes Medical Institute, Chevy Chase, Maryland, United States of America.
  • Waldor MK; Division of Infectious Diseases, Brigham & Women's Hospital and Department of Microbiology and Immunobiology, Harvard Medical School, Boston, Massachusetts, United States of America; Howard Hughes Medical Institute, Chevy Chase, Maryland, United States of America.
PLoS Genet ; 10(6): e1004433, 2014 Jun.
Article en En | MEDLINE | ID: mdl-24945690
ABSTRACT
The bacterial cell wall, which is comprised of a mesh of polysaccharide strands crosslinked via peptide bridges (peptidoglycan, PG), is critical for maintenance of cell shape and survival. PG assembly is mediated by a variety of Penicillin Binding Proteins (PBP) whose fundamental activities have been characterized in great detail; however, there is limited knowledge of the factors that modulate their activities in different environments or growth phases. In Vibrio cholerae, the cause of cholera, PG synthesis during the transition into stationary phase is primarily mediated by the bifunctional enzyme PBP1A. Here, we screened an ordered V. cholerae transposon library for mutants that are sensitive to growth inhibition by non-canonical D-amino acids (DAA), which prevent growth and maintenance of cell shape in PBP1A-deficient V. cholerae. In addition to PBP1A and its lipoprotein activator LpoA, we found that CsiV, a small periplasmic protein with no previously described function, is essential for growth in the presence of DAA. Deletion of csiV, like deletion of lpoA or the PBP1A-encoding gene mrcA, causes cells to lose their rod shape in the presence of DAA or the beta-lactam antibiotic cefsulodin, and all three mutations are synthetically lethal with deletion of mrcB, which encodes PBP1B, V. cholerae's second key bifunctional PBP. CsiV interacts with LpoA and PG but apparently not with PBP1A, supporting the hypothesis that CsiV promotes LpoA's role as an activator of PBP1A, and thereby modulates V. cholerae PG biogenesis. Finally, the requirement for CsiV in PBP1A-mediated growth of V. cholerae can be overcome either by augmenting PG synthesis or by reducing PG degradation, thereby highlighting the importance of balancing these two processes for bacterial survival.
Asunto(s)

Texto completo: 1 Banco de datos: MEDLINE Asunto principal: Proteínas Bacterianas / Vibrio cholerae / Pared Celular / Proteínas de Unión a las Penicilinas / Peptidoglicano Glicosiltransferasa Idioma: En Revista: PLoS Genet Asunto de la revista: GENETICA Año: 2014 Tipo del documento: Article País de afiliación: Estados Unidos

Texto completo: 1 Banco de datos: MEDLINE Asunto principal: Proteínas Bacterianas / Vibrio cholerae / Pared Celular / Proteínas de Unión a las Penicilinas / Peptidoglicano Glicosiltransferasa Idioma: En Revista: PLoS Genet Asunto de la revista: GENETICA Año: 2014 Tipo del documento: Article País de afiliación: Estados Unidos