Lipid lysination by MprF contributes to hemolytic pigment retention in group B Streptococcus.

Group B Streptococcus (GBS) is the leading cause of neonatal sepsis and meningitis. A major virulence factor is a pigmented beta-haemolytic/cyto-lysin (β-h/c) toxin with an ornithine rhamnolipid structure. We initially observed that absence of MprF enzyme altered pigmentation and haemolytic activity in GBS. Next, we showed that MprF-dependent lipid lysination contributes to the retention of the ornithine rhamnolipid within GBS membrane. Furthermore, cationic lipidation by MprF altered membrane properties contributing to resistance to the cyclic lipopeptide daptomycin and to acidic pH. This study highlights the importance of cationic lipids in cell envelope homeostasis and in modulating β-h/c activity.

Caliot E ，Firon A ，Solgadi A ，Trieu-Cuot P ，Dramsi S ... -  《-》

Group B Streptococcal Hemolytic Pigment Impairs Platelet Function in a Two-Step Process.

Jahn K ，Shumba P ，Quach P ，Müsken M ，Wesche J ，Greinacher A ，Rajagopal L ，Hammerschmidt S ，Siemens N ... -  《Cells》

Group B streptococcal haemolysin and pigment, a tale of twins.

Group B streptococcus [(GBS or Streptococcus agalactiae)] is a leading cause of neonatal meningitis and septicaemia. Most clinical isolates express simultaneously a β-haemolysin/cytolysin and a red polyenic pigment, two phenotypic traits important for GBS identification in medical microbiology. The genetic determinants encoding the GBS haemolysin and pigment have been elucidated and the molecular structure of the pigment has been determined. The cyl operon involved in haemolysin and pigment production is regulated by the major two-component system CovS/R, which coordinates the expression of multiple virulence factors of GBS. Genetic analyses indicated strongly that the haemolysin activity was due to a cytolytic toxin encoded by cylE. However, the biochemical nature of the GBS haemolysin has remained elusive for almost a century because of its instability during purification procedures. Recently, it has been suggested that the haemolytic and cytolytic activity of GBS is due to the ornithine rhamnopolyenic pigment and not to the CylE protein. Here we review and summarize our current knowledge of the genetics, regulation and biochemistry of these twin GBS phenotypic traits, including their functions as GBS virulence factors.

Rosa-Fraile M ，Dramsi S ，Spellerberg B 《-》

The cyl Genes Reveal the Biosynthetic and Evolutionary Origins of the Group B Streptococcus Hemolytic Lipid, Granadaene.

Group B Streptococcus (GBS) is a β-hemolytic, Gram-positive bacterium that commonly colonizes the female lower genital tract and is associated with fetal injury, preterm birth, spontaneous abortion, and neonatal infections. A major factor promoting GBS virulence is the β-hemolysin/cytolysin, which is cytotoxic to several host cells. We recently showed that the ornithine rhamnolipid pigment, Granadaene, produced by the gene products of the cyl operon, is hemolytic. Here, we demonstrate that heterologous expression of the GBS cyl operon conferred hemolysis, pigmentation, and cytoxicity to Lactococcus lactis, a model non-hemolytic Gram-positive bacterium. Similarly, pigment purified from L. lactis is hemolytic, cytolytic, and identical in structure to Granadaene extracted from GBS, indicating the cyl operon is sufficient for Granadaene production in a heterologous host. Using a systematic survey of phyletic patterns and contextual associations of the cyl genes, we identify homologs of the cyl operon in physiologically diverse Gram-positive bacteria and propose undescribed functions of cyl gene products. Together, these findings bring greater understanding to the biosynthesis and evolutionary foundations of a key GBS virulence factor and suggest that such potentially toxic lipids may be encoded by other bacteria.

Armistead B ，Whidbey C ，Iyer LM ，Herrero-Foncubierta P ，Quach P ，Haidour A ，Aravind L ，Cuerva JM ，Jaspan HB ，Rajagopal L ... -  《Frontiers in Microbiology》

Hemolytic Membrane Vesicles of Group B Streptococcus Promote Infection.

Group B streptococci (GBS) are β-hemolytic, Gram-positive bacteria associated with fetal injury, preterm birth, spontaneous abortion, and neonatal infections. A key factor promoting GBS virulence is the β-hemolysin/cytolysin, a pigmented ornithine rhamnolipid (also known as granadaene) associated with the bacterial surface. A previous study indicated that GBS produce small structures known as membrane vesicles (MVs), which contain virulence-associated proteins. In this study, we show that GBS MVs are pigmented and hemolytic, indicating that granadaene is functionally active in MVs. In addition, MVs from hyperhemolytic GBS induced greater cell death of neutrophils, T cells, and B cells compared with MVs from isogenic nonhemolytic GBS, implicating MVs as a potential mechanism for granadaene-mediated virulence. Finally, hemolytic MVs reduced oxidative killing of GBS and aggravated morbidity and mortality of neonatal mice infected with GBS. These studies, taken together, reveal a novel mechanism by which GBS deploy a crucial virulence factor to promote bacterial dissemination and pathogenesis.

Armistead B ，Quach P ，Snyder JM ，Santana-Ufret V ，Furuta A ，Brokaw A ，Rajagopal L ... -  《-》