Abstract
The cell wall of Gram-positive bacteria is a complex network of surface proteins, capsular polysaccharides and wall teichoic acids (WTA) covalently linked to Peptidoglycan (PG). The absence of WTA has been associated with a reduced pathogenicity of Staphylococcus aureus (S. aureus). Here, we assessed whether this was due to increased detection of PG, an important target of innate immune receptors. Antibiotic-mediated or genetic inhibition of WTA production in S. aureus led to increased binding of the non-lytic PG Recognition Protein-SA (PGRP-SA), and this was associated with a reduction in host susceptibility to infection. Moreover, PGRP-SD, another innate sensor required to control wild type S. aureus infection, became redundant. Our data imply that by using WTA to limit access of innate immune receptors to PG, under-detected bacteria are able to establish an infection and ultimately overwhelm the host. We propose that different PGRPs work in concert to counter this strategy.
Highlights
The complex cell surface of bacteria has been directly or indirectly associated with different strategies that bacterial pathogens use to interact with the host
The results shown here indicate that in respect to Gram-positive bacteria, where the cell wall is not concealed by outer membrane, pathogen recognition, via recognition of PG, is tightly linked to host survival
The results here show that presence of wall teichoic acids (WTA) in a range of Gram-positive bacteria impaired PG Recognition Protein-SA (PGRP-SA) binding
Summary
The complex cell surface of bacteria has been directly or indirectly associated with different strategies that bacterial pathogens use to interact with the host These include acquisition of specific adhesion factors, formation of biofilms, adaptation to an intracellular environment, production of a protective capsular polysaccharide or evasion of innate immune defences (e.g. lysozyme) [1]. Such molecules include surface proteins, covalently linked or tightly associated with PG, capsular polysaccharides, usually required for the ability of different bacteria to cause disease [6] and wall teichoic acids (WTA), phosphate-rich glycopolymers involved in the resistance of bacteria to environmental stress and regulation of bacterial division [7] It is not clear how the host would be able to sense bacterial PG buried within such complex structures. S. aureus strains impaired in the expression of enzymes involved with the Author Summary
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