Staphylococcus aureus Fibronectin Binding Protein A Mediates Biofilm Development and Infection

Abstract

Implanted medical device-associated infections pose significant health risks, as they are often the result of bacterial biofilm formation. Staphylococcus aureus is a leading cause of biofilm-associated infections which persist due to mechanisms of device surface adhesion, biofilm accumulation, and reprogramming of host innate immune responses. We found that the S. aureus fibronectin binding protein A (FnBPA) is required for normal biofilm development in mammalian serum and that the SaeRS two-component system is required for functional FnBPA activity in serum. Furthermore, serum-developed biofilms deficient in FnBPA were more susceptible to macrophage invasion, and in a model of biofilm-associated implant infection, we found that FnBPA is crucial for the establishment of infection. Together, these findings show that S. aureus FnBPA plays an important role in physical biofilm development and represents a potential therapeutic target for the prevention and treatment of device-associated infections.

Intravital Multiphoton Examination of Implant-Associated Staphylococcus aureus Biofilm Infection

“…An interesting observation throughout the time course is the overall lack of phagocytosis by monocytes, dendritic cells, and neutrophils. While this is in agreement with in vitro findings (Thurlow et al, 2011 ; Gries et al, 2020 ), a paucity of phagocytosis was observed beginning on day 3 post-infection, before the robust biofilm structure was formed. Further investigation will be required to assess the role of S. aureus biofilm molecules known to affect macrophage and neutrophil phagocytic function (Scherr et al, 2015 ; Gries et al, 2016 ; Bhattacharya et al, 2018 ).…”

“…Importantly, this model and time frame permits the establishment of a robust infection associated with both the implant and surrounding tissue. As shown in Figures 2D,E , tissue and implant-associated bacterial burdens after 9 days were comparable to those observed in other S. aureus biofilm infection models (Yamada et al, 2018 ; Gries et al, 2020 ).…”

“…Productive innate immune responses are inhibited by S. aureus biofilm products, including polarizing infiltrating macrophages and recruitment of myeloid-derived suppressor cells (Scherr et al, 2015 ; Gries and Kielian, 2017 ). Moreover, the three-dimensional biofilm architecture itself presents a barrier to immune cell infiltration and phagocytosis in vitro (Thurlow et al, 2011 ; Gries et al, 2020 ). However, relatively little is known of the host-pathogen interface during S. aureus biofilm-mediated infection.…”

“…Moreover, biofilms are notoriously recalcitrant to antibiotic therapy due to metabolic heterogeneity and are well-described for their ability to resist innate immune defenses, including leukocyte invasion and phagocytosis (Thurlow et al, 2011 ; Mulcahy et al, 2014 ; Gries and Kielian, 2017 ). Three-dimensional biofilm structure not only poses a physical barrier to host immune cell infiltration and phagocytosis (Gries et al, 2020 ), but biofilm products can actively skew immune responses to enable infection persistence (Benoit et al, 2008 ; Scherr et al, 2014 ; Gries et al, 2016 ).…”

Serum proteins potentiate therapeutic efficacy of lysocin E against S. aureus

“…Therefore, although the roles of lipid II in the antimicrobial activity of lysocin E and nisin seem to differ, they share a common mechanism by which the antimicrobial activity modulated by ApoA-I via lipid II is enhanced, implying the existence of a series of similar antimicrobials. Other than ApoA-I, proteins in a host such as albumin are known to interact with bacteria 21,22 .…”