d-alanylation of lipoteichoic acids confers resistance to cationic peptides in group b streptococcus by increasing the cell wall densityd-alanylation lipoteichoic酸对阳离子肽产生了耐药性的b群链球菌细胞壁密度增加.pdf

D-Alanylation of Lipoteichoic Acids Confers Resistance to Cationic Peptides in Group B Streptococcus by Increasing the Cell Wall Density 1 2 1 1 3 4 Ron Saar-Dover , Arkadi Bitler , Ravit Nezer , Liraz Shmuel-Galia , Arnaud Firon , Eyal Shimoni , 3 1 Patrick Trieu-Cuot , Yechiel Shai * 1 Department of Biological Chemistry, The Weizmann Institute of Science, Rehovot, Israel, 2 Department of Chemical Research Support, The Weizmann Institute of ´ ´ ` ` Science, Rehovot, Israel, 3 Institut Pasteur, Unite de Biologie des Bacteries Pathogenes a Gram-Positif, CNRS-ERL3526, Paris, France, 4 Electron Microscopy Unit, The Weizmann Institute of Science, Rehovot, Israel Abstract Cationic antimicrobial peptides (CAMPs) serve as the first line of defense of the innate immune system against invading microbial pathogens. Gram-positive bacteria can resist CAMPs by modifying their anionic teichoic acids (TAs) with D-alanine, but the exact mechanism of resistance is not fully understood. Here, we utilized various functional and biophysical approaches to investigate the interactions of the human pathogen Group B Streptococcus (GBS) with a series of CAMPs having different properties. The data reveal that: (i) D-alanylation of lipoteichoic acids (LTAs) enhance GBS resistance only to a subset of CAMPs and there is a direct correlation between resistance and CAMPs length and charge density; (ii) resistance due to reduced anionic charge of LTAs is not attributed to decreased amounts of bound peptides to the bacteria; and (iii) D- alanylation most probably alters th