STAPHYLOCOCCUS EPIDERMIDIS PRODUCES A CELL-ASSOCIATED PROTEINACEOUS FRACTION WHICH CAUSES BONE RESORPTION BY A PROSTANOID-INDEPENDENT MECHANISM: RELEVANCE TO THE TREATMENT OF INFECTED ORTHOPAEDIC IMPLANTS S. MEGHJI,* S. J. CREAN,* S. NAIR,* M. WILSON,$ S. POOLE,% M. HARRIS* and B. HENDERSON* *Maxillofacial Surgery Research Unit, $Microbiology Department, Eastman Dental Institute, University College London, 256 Gray's Inn Road, London WC1X 8LD and %Division of Endocrinology, National Institute for Biological Standards and Controls, Herts SUMMARY Staphylococcus epidermidis is the most commonly isolated coagulase-negative staphylococcus from the skin, gut and upper respiratory tract. Although it is less virulent than Staphylococcus aureus, it has emerged in recent years as an important causa- tive agent of infections associated with metal implants, prosthetic devices and i.v. lines. We have previously demonstrated that a saline wash of S. aureus contained proteins which had potent bone-resorbing activity in vitro. The purpose of this study was to determine whether gently washing S. epidermidis in saline also released osteolytically active proteins. The so- called surface-associated material (SAM) eluted from S. epidermidis in saline was able to induce osteolysis, and activity was heat and trypsin sensitive, suggesting that the active component was proteinaceous. Fractionation studies have suggested that activity is due to a small number of cationic proteins. This SAM-induced bone resorption was not inhibited by the cyclo-oxy- genase inhibitor, indomethacin, or the 5-lipoxygenase inhibitors BWA70C and MK886. However, it was partially inhibited by high concentrations of interleukin-1 receptor antagonist and was completely blocked by a neutralizing antibody to tumour necrosis factor-a. Thus, the SAM from this organism is a potent osteolytic agent which diers from that of S. aureus SAM in not being inhibited by cyclo-oxygenase inhibitors. As adjunctive therapy is becoming necessary in infectious diseases, either as a result of the side-eects of antibiotics or their lack of ecacy, consideration should be given to the future treatment of bone infections with staphylococci in the light of the dierent mechanisms of action of the surface proteins produced by these bacteria. KEY WORDS: Bone resorption, Staphylococcus epidermidis, Eicosanoids, Tumour necrosis factor, Bacterial surface proteins. OVER the past few years, Gram-positive cocci have emerged as the most prevalent cause of hospital- acquired infections [1±3]. This is due mainly to the increased incidence of bacteraemias caused by Staphylococcus epidermidis and Staphylococcus aureus [1, 2]. Staphylococcus epidermidis is a Gram-positive facultatively anaerobic bacterium, which is a univer- sal skin commensal also found in the gut and upper respiratory tract. Althugh it rarely causes infection in healthy people, it has emerged as an important pathogen in foreign body implantation such as intra- vascular catheters, devices for peritoneal dialysis, cerebrospinal ¯uid shunts, arti®cial joints and arti®- cial heart valves [4±8]. These infections are dicult to treat because the organisms are inherently resistant to many antibiotics and also form bio®lms on the prostheses which pose further diculties for anti- biotic therapy. Treatment with antibiotics alone, usually prolonged therapy with penicillinase-resistant penicillin or vancomycin, often fails, and the implant or prosthesis has to be removed [9]. Although many infections due to S. epidermidis are minor, this organism is also isolated from patients with osteomyelitis and localized bone destruction [10±12]. However, it is not known how S. epidermidis contributes to the bone destruction in these lesions. Most studies of bacterially induced bone breakdown have concentrated on the bone-modulating actions of lipopolysaccharide (LPS), a component obviously missing from S. epidermidis. In our studies of bone loss in periodontal disease, we have established that LPS from periodontopathogens is generally less active than a proteinaceous fraction which is loosely associated with the surface of these bacteria and which can be removed by stirring them gently in normal saline [13±16]. This so-called surface-asso- ciated material (SAM) consists of components such as the capsule, ®mbriae and pili, and its removal does not damage the bacteria, nor aect their viability. The SAM appears to be an important virulence fac- tor in the bone destruction which is the hallmark of the periodontal diseases. We have recently identi®ed the bone-resorbing activity in the SAM of the perio- dontopathic bacterium, Actinobacillus actinomycetem- comitans, as chaperonin 60, a member of the protein- British Journal of Rheumatology 1997;36:957±963 957 # 1997 British Society for Rheumatology Submitted 5 September 1995; revised version accepted 5 March 1997. Correspondence to: S. Meghji, Department of Oral and Maxillofacial Surgery, Eastman Dental Institute, University College London, 256 Gray's Inn Road, London WC1X 8LD.