D-Alanylation of Lipoteichoic Acids Confers Resistance to Cationic Peptides in Group B Streptococcus by Increasing the Cell Wall Density

• DOI: 10.1371/journal.ppat.1002891
• Publication Date: 2012-09-06T21:29:37Z
• Authors: Ron Saar-Dover; Arkadi Bitler; Ravit Nezer; Liraz Shmuel-Galia; Arnaud Firon; Eyal Shimoni; Patrick Trieu-Cuot; Yechiel Shai
• Keywords: Lipoteichoic acid; Teichoic acid

Cationic antimicrobial peptides (CAMPs) serve as the first line of defense innate immune system against invading microbial pathogens. Gram-positive bacteria can resist CAMPs by modifying their anionic teichoic acids (TAs) with D-alanine, but exact mechanism resistance is not fully understood. Here, we utilized various functional and biophysical approaches to investigate interactions human pathogen Group B Streptococcus (GBS) a series having different properties. The data reveal that: (i) D-alanylation lipoteichoic (LTAs) enhance GBS only subset there direct correlation between length charge density; (ii) due reduced LTAs attributed decreased amounts bound bacteria; (iii) most probably alters conformation which results in increasing cell wall density, seen Transmission Electron Microscopy, reduces penetration through wall. Furthermore, Atomic Force Microscopy reveals increased surface rigidity wild-type strain more than 20-fold that dltA mutant. We propose confers protection linear mainly decreasing flexibility permeability wall, rather reducing electrostatic peptide surface. Overall, our findings uncover an important protective role extend understanding mechanisms bacterial resistance.