Quorum-sensing molecules, also known as autoinducer, are essential for bacterial biofilm formation. Our focus is on N-(3-oxododecanoyl)-L-homoserine lactone (AHL-12), because it is also known as an ‘interkingdom signalling molecule’, which means that it also interacts with mammalian cells. AHL-12 activates defence-relevant functions of phagocytic cells, including enhancement of phagocytosis, increased expression of adhesion receptors and induction of chemotaxis. This leads to the hypothesis that early recognition of developing biofilms might be the key to a successful host defence against biofilm infection. In that context we studied activation of phagocytic cells by AHL-12, and found that phagocytes are activated via a rather specialized receptor that was not previously described on myeloid cells, the bitter taste receptor T2R38. Taste receptors are commonly associated with cells of the gustatory system. The extragustatory expression, however, suggests an additional role, namely the sensing of the onset of bacterial biofilm infection.

Implant infections are a major complication in the field of orthopaedics. Bacteria attach to the implant-surface and form biofilm-colonies which makes them difficult to treat. Not only immune cells exclusively respond to bacterial challenges, but also local tissue cells are capable of participating in defense mechanisms. The aim of this study was to evaluate the role of osteoblasts in the context of implant infections. Primary osteoblasts were cultivated and stimulated with free-swimming bacteria at 4 °C and 37 °C. Supernatants were harvested for ELISA and expression of pro-inflammatory cytokines evaluated by RT-PCR. Bacterial binding to osteoblasts was evaluated using cytofluorometry and uptake was investigated by 3H thymidine-labelling of bacteria. Osteoblasts were additionally stimulated with the extracellular polymeric substance (EPS) of Staphylococcus epidermidis biofilms, as well as components of the EPS; the bacterial heat shock protein GroEL in particular. We demonstrated that binding of bacteria to the osteoblast cell surface leads to an increased production of pro-inflammatory cytokines. Bacteria are capable of surviving intracellular. Furthermore, osteoblasts do not only respond to free-swimming, planktonic bacteria, but also to components of the EPS, including lipoteichoic acid and the heat shock protein GroEL. In conclusion, local tissue cells, specifically osteoblasts, might contribute to the persistence of the inflammatory response associated with implant-infections.

Metal-on-metal implants are a special form of hip endoprostheses that despite many advantages can entail serious complications due to release of wear particles from the implanted material. Metal wear particles presumably activate local host defence mechanisms, which causes a persistent inflammatory response with destruction of bone followed by a loosening of the implant. To better characterize this inflammatory response and to link inflammation to bone degradation, the local generation of proinflammatory and osteoclast-inducing cytokines was analysed, as was systemic T cell activation.

Bone infections of patients with joint replacement by endoprosthesis (so called “periprosthetic joint infection”) pose a severe problem in the field of orthopedic surgery. The diagnosis is often difficult, and treatment is, in most cases, complicated and prolonged. Patients often require an implant exchange surgery, as the persistent infection and the accompanying inflammation lead to tissue damage with bone degradation and consequently, to a loosening of the implant. To gain insight into the local inflammatory process, expression of the proinflammatory cytokine MRP-14, a major content of neutrophils, and its link to subsequent bone degradation was evaluated. We found MRP-14 prominently expressed in the affected tissue of patients with implant-associated infection, in close association with the chemokine CXCL8 and a dense infiltrate of neutrophils and macrophages. In addition, the number of MRP-14-positive cells correlated with the presence of bone-resorbing osteoclasts. MRP-14 plasma concentrations were significantly higher in patients with implant-associated infection compared with patients with sterile inflammation or healthy individuals, advocating MRP-14 as a novel diagnostic marker. A further biologic activity of MRP-14 was detected: rMRP-14 directly induced the differentiation of monocytes to osteoclasts, thus linking the inflammatory response in implant infections with osteoclast generation, bone degradation, and implant loosening.

Impaired fracture healing, especially when associated with bacterial infection, is a severe complication following long-bone fractures and requires special treatment. Because standard diagnostic techniques might provide falsely negative results, we evaluated the sonication method for detection of bacteria on implants of patients with fracture nonunions. A total of 49 patients with a nonunion (group NU) and, for comparison, 45 patients who had undergone routine removal of osteosynthetic material (group OM), were included in the study. Five different diagnostic methods (culture of tissue samples, culture of intraoperative swabs, histopathology of tissue samples, culture of sonication fluid, and 16S ribosomal DNA polymerase chain reaction of sonication fluid) were compared and related to clinical data. Among the diagnostic tests, culture of sonication fluid demonstrated by far the highest detection rate of bacteria (57%) in group NU, and rather unexpectedly 40% in group OM. Culture of sonication samples also revealed a broad spectrum of bacteria, in particular Propionibacterium spp. In conclusion, our results indicate that more bacteria can be detected on implants of patients with atrophic nonunions of long-bone fractures by means of the sonication procedure, which provides a valuable additional diagnostic tool to decide on a surgical procedure (eg, two-step procedure) and to further specify antimicrobial therapy.

The aim of this study was to evaluate bacteria species detected in a large number of patients treated for prosthetic joint infection of the hip and knee at a single specialized center. Furthermore, the rate of implant loosening was investigated in a time-dependent manner for the most frequently detected bacteria species. A retrospective analysis of patients (n = 209) treated for prosthetic joint infection of the hip and knee was performed. The following parameters were evaluated: C-Reactive Protein (CRP) concentration, microbiological evaluation of tissue samples, loosening of the implant, the time that had elapsed since the primary prosthetic joint replacement, and the duration since the last surgical intervention. Coagulase-negative Staphylococcus spp. were most frequently detected, followed by Staphylococcus aureus. Differences in CRP concentration were detected among various bacteria species. Osteolysis was not associated with one causative agent in particular. Patients who had undergone previous revision surgery had a higher probability of implant loosening. Coagulase-negative Staphylococcus spp. are the most common causative agents of prosthetic joint infection and show no significant differences with regard to implant loosening or the time-course when compared to S. aureus. Infections with Enterococcus spp. seem to develop faster than with other bacteria species. The risk of implant loosening increases with revision surgery, in particular in the hip joint.