Elucidating the Crucial Role of Poly N-Acetylglucosamine from Staphylococcus aureus in Cellular Adhesion and Pathogenesis

Abstract

Staphylococcus aureus is an important pathogen that forms biofilms on the surfaces of medical implants. Biofilm formation by S. aureus is associated with the production of poly N-acetylglucosamine (PNAG), also referred to as polysaccharide intercellular adhesin (PIA), which mediates bacterial adhesion, leading to the accumulation of bacteria on solid surfaces. This study shows that the ability of S. aureus SA113 to adhere to nasal epithelial cells is reduced after the deletion of the ica operon, which contains genes encoding PIA/PNAG synthesis. However, this ability is restored after a plasmid carrying the entire ica operon is transformed into the mutant strain, S. aureus SA113Δica, showing that the synthesis of PIA/PNAG is important for adhesion to epithelial cells. Additionally, S. carnosus TM300, which does not produce PIA/PNAG, forms a biofilm and adheres to epithelial cells after the bacteria are transformed with a PIA/PNAG-expressing plasmid, pTXicaADBC. The adhesion of S. carnosus TM300 to epithelial cells is also demonstrated by adding purified exopolysaccharide (EPS), which contains PIA/PNAG, to the bacteria. In addition, using a mouse model, we find that the abscess lesions and bacterial burden in lung tissues is higher in mice infected with S. aureus SA113 than in those infected with the mutant strain, S. aureus SA113Δica. The results indicate that PIA/PNAG promotes the adhesion of S. aureus to human nasal epithelial cells and lung infections in a mouse model. This study elucidates a mechanism that is important to the pathogenesis of S. aureus infections.

A novel in vitro model for haematogenous spreading ofS. aureusdevice biofilms demonstrating clumping dispersal as an advantageous dissemination mechanism

“…Indeed, the fibrin content of the biofilm clumps might strengthen the endothelial adhesion as previously observed for microthrombi formed by spontaneous aggregation in culture (Claes et al, ). PNAG in the biofilm thromboemboli might also contribute to increased adhesion via electrostatic attraction between PNAG and endothelial cells, similar to what was recently suggested by Lin et al (). Apart from adhesion, fibrin formation has also been implicated in phagocytosis evasion, by acting as a fibrin shield around growing colonies (Guggenberger, Wolz, Morrissey, & Heesemann, ; Thomer et al, ).…”

The Active Component of Aspirin, Salicylic Acid, Promotes Staphylococcus aureus Biofilm Formation in a PIA-dependent Manner

“…Because formation of S. aureus biofilm was demonstrated in vivo in both human and murine nasal mucosa (Zernotti et al, 2010; Muthukrishnan et al, 2011; Reddinger et al, 2016) and since PIA contributes significantly to the adherence of S. aureus to nasal epithelial cells (Lin et al, 2015) we investigated the effect of SAL in vivo using a nasal colonization murine model. Groups of mice received 200 μl of 2 mM of SAL or PBS (control) by the intravenous route 30 min before bacterial inoculum.…”

“…Moreover, Lin et al (2015) reported a significant contribution of PIA to the adherence of S. aureus to nasal epithelial cells. Additionally, nasal colonization with the Newman strain was registered for long periods in a model of nasal colonization using humanized transgenic mice (Xu et al, 2015).…”

Staphylococcus aureus Aggregation and Coagulation Mechanisms, and Their Function in Host–Pathogen Interactions

“…Several studies have focused on the contribution of PIA to biofilm formation, where there is a great deal of heterogeneity between strains and infection sites. There are examples where the icaADBC locus is required for biofilm formation in vivo (Lin et al, 2015; Vuong et al, 2004a), as well as cases where the biofilm matrix appears to be predominantly composed of protein and DNA, and PIA production is dispensable for virulence (Beenken et al, 2004; Schaeffer et al, 2015; Vergara-Irigaray et al, 2009). One of the main advantages of biofilm formation is enhanced tolerance of some antibiotics, with S. aureus exhibiting 100–1000 fold higher MICs (Ceri et al, 1999).…”