Lipid analogs reveal features critical for hemolysis and diminish granadaene mediated Group B Streptococcus infection Armistead, Blair Herrero-Foncubierta, Pilar Tapia, Rubén Casares, Raquel Millán, Alba Haidour, Ali Cuerva Carvajal, Juan Manuel Justicia Ladrón De Guevara, José Although certain microbial lipids are toxins, the structural features important for cytotoxicity remain unknown. Increased functional understanding is essential for developing therapeutics against toxic microbial lipids. Group B Streptococci (GBS) are bacteria associated with preterm births, stillbirths, and severe infections in neonates and adults. GBS produce a pigmented, cytotoxic lipid, known as granadaene. Despite its importance to all manifestations of GBS disease, studies towards understanding granadaene’s toxic activity are hindered by its instability and insolubility in purified form. Here, we report the synthesis and screening of lipid derivatives inspired by granadaene, which reveal features central to toxin function, namely the polyene chain length. Furthermore, we show that vaccination with a non-toxic synthetic analog confers the production of antibodies that inhibit granadaene-mediated hemolysis ex vivo and diminish GBS infection in vivo. This work provides unique structural and functional insight into granadaene and a strategy to mitigate GBS infection, which will be relevant to other toxic lipids encoded by human pathogens. 2020-04-21T11:55:48Z 2020-04-21T11:55:48Z 2020 info:eu-repo/semantics/article Armistead, B., Herrero-Foncubierta, P., Coleman, M., Quach, P., Whidbey, C., Justicia, J., ... & Granger, J. R. (2020). Lipid analogs reveal features critical for hemolysis and diminish granadaene mediated Group B Streptococcus infection. Nature communications, 11(1), 1-12. http://hdl.handle.net/10481/61414 10.1038/s41467-020-15282-0 eng http://creativecommons.org/licenses/by/3.0/es/ info:eu-repo/semantics/openAccess Atribución 3.0 España Springer Nature