Utilize este identificador para referenciar este registo:
https://hdl.handle.net/10216/114513
Autor(es): | Carvalho, F Atilano, ML Pombinho, R Covas, G Gallo, RL Filipe, SR Sousa, S Cabanes, D |
Título: | L-Rhamnosylation of Listeria monocytogenes Wall Teichoic Acids Promotes Resistance to Antimicrobial Peptides by Delaying Interaction with the Membrane |
Editor: | Public Library of Science |
Data de publicação: | 2015 |
Resumo: | 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 Grampositive 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 Lrhamnose, 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. |
Assunto: | Animals Anti-Infective Agents/pharmacology Antimicrobial Cationic Peptides/pharmacology Cell Membrane/metabolism Cell Wall/metabolism Cells, Cultured Drug Resistance, Bacterial/drug effects Glycosylation Humans Listeria monocytogenes/physiology Listeriosis/drug therapy Listeriosis/microbiology Macrophages/drug effects Macrophages/microbiology Mice Mice, Inbred BALB C Rhamnose/chemistry Teichoic Acids/pharmacology Virulence |
URI: | http://hdl.handle.net/10216/114513 |
Fonte: | PLoS pathogens, vol. 11(5):e1004919 |
Informação Relacionada: | info:eu-repo/grantAgreement/FCT/3599-PPCDT/111806/PT info:eu-repo/grantAgreement/FCT/3599-PPCDT/137216/PT info:eu-repo/grantAgreement/FCT/SFRH/SFRH%2FBD%2F61825%2F2009/PT info:eu-repo/grantAgreement/FCT/SFRH/SFRH%2FBD%2F28440%2F2006/PT info:eu-repo/grantAgreement/FCT/SFRH/SFRH%2FBD%2F89542%2F2012/PT |
Tipo de Documento: | Artigo em Revista Científica Internacional |
Condições de Acesso: | openAccess |
Licença: | https://creativecommons.org/licenses/by/4.0/ |
Aparece nas coleções: | I3S - Artigo em Revista Científica Internacional |
Ficheiros deste registo:
Ficheiro | Descrição | Tamanho | Formato | |
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Carvalho 2015.pdf | 1.23 MB | Adobe PDF | Ver/Abrir |
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