Abstract
Implicated in more than 60% of bone and joint infections (BJIs), Staphylococci have a particular tropism for osteoarticular tissue and lead to difficult-to-treat clinical infections. To date, Staphylococcus aureus internalization in non-professional phagocytic cells (NPPCs) is a well-explored virulence mechanism involved in BJI chronicity. Conversely, the pathophysiological pathways associated with Staphylococcus non-aureus (SNA) BJIs have scarcely been studied despite their high prevalence. In this study, 15 reference strains from 15 different SNA species were compared in terms of (i) adhesion to human fibronectin based on adhesion microplate assays and (ii) internalization ability, intracellular persistence and cytotoxicity based on an in vitro infection model using human osteoblasts. Compared to S. aureus, S. pseudintermedius was the only species that significantly adhered to human fibronectin. This species was also associated with high (even superior to S. aureus) internalization ability, intracellular persistence and cytotoxicity. These findings were confirmed using a panel of 17 different S. pseudintermedius isolates. Additionally, S. pseudintermedius internalization by osteoblasts was completely abolished in β1 integrin-deficient murine osteoblasts. These results suggest the involvement of β1 integrin in the invasion process, although this mechanism was previously restricted to S. aureus. In summary, our results suggest that internalization into NPPCs is not a classical pathophysiologic mechanism of SNA BJIs. S. pseudintermedius appears to be an exception, and its ability to invade and subsequently induce cytotoxicity in NPPCs could explain its severe and necrotic forms of infection, notably in dogs, which exhibit a high prevalence of S. pseudintermedius infection.
Highlights
Bone and joint infections (BJIs) represent a major public health issue, with an annual mortality rate near 5% and a classically reported relapse rate of 20–30% that can reach 80% in specific populations (Lentino, 2003)
Two key mechanisms have been identified to explain the high rate of treatment failure of S. aureus bone and joint infections (BJIs): (i) the formation of biofilm, which is defined as the community of microbes that adhere to a biotic or an abiotic surface and that are covered by an adhesive protective matrix, and (ii) internalization and sanctuarization by which invasive bacteria actively induce their own uptake by phagocytosis into host cells, where they establish a protected niche within which they can replicate
Screening of a large panel of Staphylococcus non-aureus (SNA) species showed that persistence in non-professional phagocytic cells (NPPCs) is likely not a widespread and predominant pathophysiologic pathway underlying the chronicity of infection with SNA, especially BJI
Summary
Bone and joint infections (BJIs) represent a major public health issue, with an annual mortality rate near 5% and a classically reported relapse rate of 20–30% that can reach 80% in specific populations (Lentino, 2003). We previously demonstrated using a large panel of clinical isolates that the extent of invasion in an in vitro infection model were so low that this mechanism is likely not involved in BJI with S. epidermidis (Valour et al, 2013). In the same way, Hussain et al (2015) suggested that the S. lugdunensis invasion of endothelial, epithelial and fibroblastic cells is mediated by the bacterial autolysin AtlL whereas Campoccia et al (2015) reported no internalization of this pathogen by human osteoblasts. In addition to these controversies, this issue remains under debate for all other Staphylococci species
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