Wall Teichoic Acid Glycosylation Governs Staphylococcus aureus Nasal Colonization

Abstract

Nasal colonization by the human pathogen Staphylococcus aureus is a major risk factor for hospital- and community-acquired infections. A key factor required for nasal colonization is a cell surface-exposed zwitterionic glycopolymer, termed wall teichoic acid (WTA). However, the precise mechanisms that govern WTA-mediated nasal colonization have remained elusive. Here, we report that WTA GlcNAcylation is a pivotal requirement for WTA-dependent attachment of community-acquired methicillin-resistant S. aureus (MRSA) and emerging livestock-associated MRSA to human nasal epithelial cells, even under conditions simulating the nutrient composition and dynamic flow of nasal secretions. Depending on the S. aureus strain, WTA O-GlcNAcylation occurs in either α or β configuration, which have similar capacities to mediate attachment to human nasal epithelial cells, suggesting that many S. aureus strains maintain redundant pathways to ensure appropriate WTA glycosylation. Strikingly, a lack of WTA glycosylation significantly abrogated the ability of MRSA to colonize cotton rat nares in vivo. These results indicate that WTA glycosylation modulates S. aureus nasal colonization and may help to develop new strategies for eradicating S. aureus nasal colonization in the future.

Metagenome analysis of Russian and Georgian Pyophage cocktails and a placebo‐controlled safety trial of single phage versus phage cocktail in healthy Staphylococcus aureus carriers

“…The development of clinical relevant phage resistance by WTA mutation is unlikely as it is a key factor for nasal colonization by S. aureus (Winstel et al ., ). Loss of a virulence factor as phage receptor thus decreases the virulence of phage‐resistant bacteria, as previously observed in other phage‐pathogen systems (Smith and Huggins, Winstel et al ., ; Oechslin et al ., ). A phage therapy approach to target S. aureus is thus possible with a single phage – much unlike the high number of different phage types needed to target E. coli isolates, which frequently target lipopolysaccharides as bacterial receptors, an essential, but highly variable virulence factor (Chibani‐Chennoufi et al ., ; Tanji et al ., ; Bourdin et al ., ).…”

“…Phage K, the prototype of Kayviruses, binds to the highly-conserved wall-teichoic acids (WTA) on the surface of the S. aureus cell wall, which explains its broad host range (O'Flaherty et al, 2005;Xia et al, 2011). The development of clinical relevant phage resistance by WTA mutation is unlikely as it is a key factor for nasal colonization by S. aureus (Winstel et al, 2015). Loss of a virulence factor as phage receptor thus decreases the virulence of phage-resistant bacteria, as previously observed in other phage-pathogen systems (Smith andHuggins, 1982 Winstel et al, 2015;Oechslin et al, 2016).…”

Listeria monocytogenes wall teichoic acid decoration in virulence and cell‐to‐cell spread

“…The authors found that mutants lacking this decoration show attenuation and become more sensitive to antimicrobial peptides. Also recently, in S. aureus , an important role for WTA decoration was shown for site‐specific colonization (Winstel et al ., ). Additionally, interest is growing in small molecule inhibitors of virulence functions (often termed antiviurlence factors or virulence blockers) to be used as replacements for antibiotics, or as adjuncts that enhance antibiotic action (Chung and Toh, ; Rasko and Sperandio, ).…”

“…Wall teichoic acid (WTA) comprises a class of glycopolymers that are covalently attached to the peptidoglycan walls of gram positive bacteria (Brown et al ., ). The repeated polymeric units often have non‐essential sugar substituents (decorations) whose absence frequently prevents bacteriophage (phage) binding (Lindberg, ), influences antigenicity (Uchikawa et al ., ), sensitivity to wall‐acting antibiotics (Brown et al ., ), tissue tropism (Winstel et al ., ) and virulence (Autret et al ., ; Faith et al ., ; Spears et al ., ). The biochemical steps involved in decoration addition (referred to as tailoring) are unique to the type of WTA polymeric backbone being modified and the decorating sugar involved.…”

Structure and Mechanism of Staphylococcus aureus TarS, the Wall Teichoic Acid β-glycosyltransferase Involved in Methicillin Resistance

“…aureus WTA, regardless of linkage conformation [71]. This redundancy in addition appears to be relevant in other processes such as colonization, where it has recently been found that WTA O-GlcNAcylation with either an α or β linkage is pivotal to the attachment of MRSA strains to human nasal epithelial cells [72], a process that contributes to the spread of nosocomial and community-acquired infections.…”