L-Rhamnosylation of Listeria monocytogenes Wall Teichoic Acids Promotes Resistance to Antimicrobial Peptides by Delaying Interaction with the Membrane.
| Title: | L-Rhamnosylation of Listeria monocytogenes Wall Teichoic Acids Promotes Resistance to Antimicrobial Peptides by Delaying Interaction with the Membrane. |
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| Authors: | Filipe Carvalho, Magda L Atilano, Rita Pombinho, Gonçalo Covas, Richard L Gallo, Sérgio R Filipe, Sandra Sousa, Didier Cabanes |
| Source: | PLoS Pathogens, Vol 11, Iss 5, p e1004919 (2015) |
| Publisher Information: | Public Library of Science (PLoS), 2015. |
| Publication Year: | 2015 |
| Collection: | LCC:Immunologic diseases. Allergy LCC:Biology (General) |
| Subject Terms: | Immunologic diseases. Allergy, RC581-607, Biology (General), QH301-705.5 |
| More Details: | Listeria monocytogenes is an opportunistic Gram-positive bacterial pathogen responsible for listeriosis, a human foodborne disease. Its cell wall is densely decorated with wall teichoic acids (WTAs), a class of anionic glycopolymers that play key roles in bacterial physiology, including protection against the activity of antimicrobial peptides (AMPs). In other Gram-positive pathogens, WTA modification by amine-containing groups such as D-alanine was largely correlated with resistance to AMPs. However, in L. monocytogenes, where WTA modification is achieved solely via glycosylation, WTA-associated mechanisms of AMP resistance were unknown. Here, we show that the L-rhamnosylation of L. monocytogenes WTAs relies not only on the rmlACBD locus, which encodes the biosynthetic pathway for L-rhamnose, but also on rmlT encoding a putative rhamnosyltransferase. We demonstrate that this WTA tailoring mechanism promotes resistance to AMPs, unveiling a novel link between WTA glycosylation and bacterial resistance to host defense peptides. Using in vitro binding assays, fluorescence-based techniques and electron microscopy, we show that the presence of L-rhamnosylated WTAs at the surface of L. monocytogenes delays the crossing of the cell wall by AMPs and postpones their contact with the listerial membrane. We propose that WTA L-rhamnosylation promotes L. monocytogenes survival by decreasing the cell wall permeability to AMPs, thus hindering their access and detrimental interaction with the plasma membrane. Strikingly, we reveal a key contribution of WTA L-rhamnosylation for L. monocytogenes virulence in a mouse model of infection. |
| Document Type: | article |
| File Description: | electronic resource |
| Language: | English |
| ISSN: | 1553-7366 1553-7374 |
| Relation: | http://europepmc.org/articles/PMC4441387?pdf=render; https://doaj.org/toc/1553-7366; https://doaj.org/toc/1553-7374 |
| DOI: | 10.1371/journal.ppat.1004919 |
| Access URL: | https://doaj.org/article/df7c24b2fd2c468d8c8b8d8bc20cd231 |
| Accession Number: | edsdoj.f7c24b2fd2c468d8c8b8d8bc20cd231 |
| Database: | Directory of Open Access Journals |
| ISSN: | 15537366 15537374 |
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| DOI: | 10.1371/journal.ppat.1004919 |
| Published in: | PLoS Pathogens |
| Language: | English |