A potential key role for alpha-haemolysin of Staphylococcus aureus in mediating chondrocyte death in septic arthritis

Bone & Joint Research

article

I. D. M. Smith¹  K. M. Milto²  C. J. Doherty³  S. G. B. Amyes³  A. H. R. W. Simpson⁴  A. C. Hall² 

[1]Institute of Infection, Immunity and Inflammation, University of Glasgow

[2]Centre for Integrative Physiology, University of Edinburgh

[3]Department of Medical Microbiology, University of Edinburgh

[4]Musculoskeletal Research Unit, Department of Orthopaedic Surgery, University of Edinburgh

关键词: Septic arthritis;    Articular cartilage;    Chondrocyte death;    Haemolysins;    Confocal microscopy;   

DOI  :  10.1302/2046-3758.77.BJR-2017-0165.R1

学科分类：骨科学

来源: British Editorial Society Of Bone And Joint Surgery

【 摘 要 】

ObjectivesStaphylococcus aureus (S. aureus) is the most commonly implicated organism in septic arthritis, a condition that may be highly destructive to articular cartilage. Previous studies investigating laboratory and clinical strains of S. aureus have demonstrated that potent toxins induced significant chondrocyte death, although the precise toxin or toxins that were involved was unknown. In this study, we used isogenic S. aureus mutants to assess the influence of alpha (Hla)-, beta (Hlb)-, and gamma (Hlg)-haemolysins, toxins considered important for the destruction of host tissue, on in situ bovine chondrocyte viability.MethodsBovine cartilage explants were cultured with isogenic S. aureus mutants and/or their culture supernatants. Chondrocyte viability was then assessed within defined regions of interest in the axial and coronal plane following live- and dead-cell imaging using the fluorescent probes 5-chloromethylfluorescein diacetate and propidium iodide, respectively, and confocal laser-scanning microscopy.ResultsHla-producing mutants caused substantial chondrocyte death compared with the toxin-deficient control (Hla-Hlb-Hlg-), whilst mutants producing Hlb and Hlg in the absence of Hla induced minimal chondrocyte death. Coronal studies established that Hla-induced chondrocyte death started in the superficial zone of cartilage and spread to deeper layers, whereas Hlb and Hlg toxins were without significant effect.ConclusionThis study identified Hla as a highly potent S. aureus toxin that caused rapid chondrocyte death in bovine cartilage, with other toxins or metabolic products produced by the bacteria playing a minor role. The identification of Hla in mediating chondrocyte death may assist in the development of therapeutic strategies aimed at reducing the extent of cartilage damage during and after an episode of septic arthritis.

【 授权许可】

CC BY-NC