Wall teichoic acids mediate increased virulence in Staphylococcus aureus

Abstract

Community-associated methicillin-resistant Staphylococcus aureus (CA-MRSA) are the cause of a severe pandemic consisting primarily of skin and soft tissue infections. The underlying pathomechanisms have not been fully understood and we report here a mechanism that plays an important role for the elevated virulence of CA-MRSA. Surprisingly, skin abscess induction in an animal model was correlated with the amount of a major cell wall component of S. aureus, termed wall teichoic acid (WTA). CA-MRSA exhibited increased cell-wall-associated WTA content (WTA) and thus were more active in inducing abscess formation via a WTA-dependent and T-cell-mediated mechanism than S. aureus strains with a WTA phenotype. We show here that WTA is directly involved in S. aureus strain-specific virulence and provide insight into the underlying molecular mechanisms that could guide the development of novel anti-infective strategies.

Reducing Staphylococcus aureus resistance to lysostaphin using CRISPR‐dCas9

“…WTAs in S. aureus are involved in the development of cellular resistance to many antimicrobial agents, such as immune cells and antimicrobial peptides, due to the dynamic change in the structure or content of WTA present on the cell surface (Wanner et al, ). To investigate if WTA contributed to such medium‐related resistance, we grew cells in TSB supplemented with 0.25 μg/ml of tunicamycin (Tun), which inhibits the first step of WTA biosynthesis catalyzed by TarO.…”

“…Previous studies have shown that WTAs induce resistance to antimicrobials in Gram‐positive bacteria via permanent genotypic variations or temporary phenotypic transitions. Genotypic variations include upregulation of WTA biosynthesis and structural modification of WTAs with D‐alanyl esters (Brown, Maria, & Walker, ; McBride & Sonenshein, ; Wanner et al, ). Phenotypic changes involving WTAs include changes in conformation and the proton gradient.…”

“…D‐Alanylation, that is, the attachment of d ‐alanine and the formation of alanyl esters with the phosphate groups regulated by the dltABCD operon, attenuates the negative charge of WTAs (Neuhaus & Baddiley, ; Peschel, ), and increases resistance to cationic antimicrobial peptides in Gram‐positive bacteria, including Clostridium difficile and Staphylococcus aureus (McBride & Sonenshein, ; Neuhaus & Baddiley, ). Clinical isolates of community‐associated methicillin‐resistant S. aureus (MRSA) have elevated expression of the tarH gene, which encodes the protein TarH responsible for the display of WTAs on the cell surface, as compared with less resistant or less virulent strains (Wanner et al, ). Inhibition of WTA biosynthesis greatly enhances S. aureus sensitivity to β lactams (Lee et al, ; Wang et al, ).…”

Staphylococcus aureuswall teichoic acid is a pathogen-associated molecular pattern that is recognized by langerin (CD207) on skin Langerhans cells

“…First of all, WTA density depends on expression of tarH, which encodes the energy generating component of the WTA ABC transporter TarGH. Importantly, the amount of WTA correlates to the ability of S. aureus to induce skin abscess formation (Wanner et al, 2017). Second, studies on lytic podophage infection of S. aureus suggest careful regulation of WTA GlcNAcylation (Li et al, 2015).…”

An Update on Clinical Burden, Diagnostic Tools, and Therapeutic Options of Staphylococcus aureus

“…Recent findings suggest that cytolytic PSM-α, cytolysin α-toxin, and the global virulence regulator ( agr ) have demonstrated important roles in experimental skin infection models 32. It was reported that high WTA amounts might permit S aureus to amplify early responses to abscess formation, thereby creating a microenvironment that protects bacteria from host responses 31. Abscess formation and colony forming unit increase was observed when purified WTA along with bacterial inoculum of WTA low producers was injected.…”