Group B Streptococcus circumvents neutrophils and neutrophil extracellular traps during amniotic cavity invasion and preterm labor

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Science Immunology  14 Oct 2016:
Vol. 1, Issue 4, eaah4576
DOI: 10.1126/sciimmunol.aah4576

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    • Lakshmi Rajagopal, Associate Professor, University of Washington and Seattle Childrens Research Institute
    • Other Contributors:
      • Christopher Whidbey, Postdoctoral Fellow, Pacific Northwest National Laboratories
      • Blair Armistead, Graduate Student, University of Washington and Seattle Childrens Research Institute

    Author’s response to Dr. Rosa Fraile’s eletter:

    We thank Dr. Rosa Fraile for his comments pertaining to our published article in Science Immunology (1). We would like to take this opportunity to formally address these comments.
    Dr. Rosa Fraile indicates that the “GBS pigment (granadaene) has been fully characterized and has cytotoxic activity, however it has not been demonstrated that this chromofore is the real GBS hemolysin”. In response to this, we would first like to indicate that in his eletter, Dr. Rosa Fraile acknowledges that the GBS pigment is fully characterized and is cytotoxic. Second, we purified the GBS pigment as described in his original paper (2) but we showed that the pigment is hemolytic and cytolytic, in the presence of stabilizers such as starch (1, 3-5). Hemolytic and cytolytic activities of the GBS pigment seen in vitro are similar to those observed with hemolytic GBS strains and are not observed in isogenic non-hemolytic GBS strains (1, 3-5). This includes the mechanism of lysis of red blood cells (3), observations of pyroptosis in macrophages (4), and cell death of neutrophils (1) and mast cells (5), Therefore, we conclude that the pigment is the GBS hemolysin, if not the major component of the GBS hemolysin.
    While it is true that addition of stabilizers such as starch are needed to observe the hemolytic and cytolytic activity of the purified pigment in vitro, this is also true when hemolysin is isolated in the form of crude (aqu...

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    Competing Interests: None declared.
    • Manuel Rosa-Fraile, Microbiologist, University Hospital Virgen de las Nieves-GRANADA-Spain

    It has been assumed that the β-hemolysin and the pigment of group B streptococcus are the same molecule because a complete link exists between them. The molecule of the chromofore of the GBS pigment (granadaene) has been fully characterized and has cytotoxic activity, however it has not been demonstrated that this chromofore is the real GBS hemolysin.

    Boldenow et al. (1) recently presented additional data proving that hemolytic GBS are more virulent than non-hemolytic strains with respect to pregnant women and that the ornithine rhamnopolyenic chromophore of the GBS pigment (granadaene) (2) is able to induce fetal injury and preterm labor.
    Nevertheless the authors postulate that the chromophore of GBS pigment is identical to the GBS hemolysin and this assumption is unrealistic. Consequently to extrapolate the cytotoxic activity of this chromophore to the GBS bacteria is speculative at best. Baldenow et al. (1) use the technique already described by Rosa-Fraile et al. (2) to extract, purify and work out the structure of the GBS pigment. This process has also been used later to purify the same pigment from Propioniobacterium jenseni by Vanberg et al. (3) who also described in their paper that granadaene was not hemolytic. Surprisingly these facts are not mentioned in the Baldenow paper (1).
    This technique, extracts the granadaene molecule from the GBS grown in Granada medium using a mixture of trifluorocetic acid and dimethilsulfoxide (DMSO...

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    Competing Interests: None declared.

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