Caenorhabditis elegans is currently introduced as a new, facile, and cheap model organism to study the pathogenesis of gram-negative bacteria such as Pseudomonas aeruginosa and Salmonella enterica serovar Typhimurium. The mechanisms of killing involve either diffusible exotoxins or infection-like processes. Recently, it was shown that also some gram-positive bacteria kill C. elegans, although the precise mechanisms of killing remained open. We examined C. elegans as a pathogenesis model for the gram-positive bacterium Streptococcus pyogenes, a major human pathogen capable of causing a wide spectrum of diseases. We demonstrate that S. pyogenes kills C. elegans, both on solid and in liquid medium. Unlike P. aeruginosa and S. enterica serovar Typhimurium, the killing by S. pyogenes is solely mediated by hydrogen peroxide. Killing required live streptococci; the killing capacity depends on the amount of hydrogen peroxide produced, and killing can be inhibited by catalase. Major exotoxins of S. pyogenes are not involved in the killing process as confirmed by using specific toxin inhibitors and knockout mutants. Moreover, no accumulation of S. pyogenes in C. elegans is observed, which excludes the involvement of infection-like processes. Preliminary results show that S. pneumoniae can also kill C. elegans by hydrogen peroxide production. Hydrogen peroxide-mediated killing might represent a common mechanism by which gram-positive, catalase-negative pathogens kill C. elegans.Streptococcus pyogenes is a major human pathogen, causing a wide spectrum of pyogenic infections such as tonsillitis, pharyngitis, scarlet fever, and skin inflammation. The organism can also invade tissues and cells and cause life-threatening diseases such as necrotizing fasciitis and toxic shock syndrome. Untreated infections can lead to serious postinfection complications in the form of rheumatic heart disease and glomerulonephritis in predisposed individuals (22). The pathogenesis of streptococci is so complex that the infections caused by these organisms and their sequelae have not been completely understood. Bacterial factors, host factors, and an abnormal immune response determine the outcome of the infection. One of the difficulties in understanding the streptococcus-host interaction is the lack of a suitable animal model. Recently a mouse model of invasive streptococcal infections has been developed (16), but there remains a great need for new animal models to understand streptococcal pathogenesis.Ausubel and coworkers have introduced Caenorhabditis elegans as a new, facile, and cheap model organism to study the pathogenesis of the gram-negative bacteria Pseudomonas aeruginosa (5,15,(23)(24)(25)27) and Salmonella enterica serovar Typhimurium (1, 2, 13), and Garsin et al. showed that the gram-positive bacteria Enterococcus faecalis and Streptococcus pneumoniae kill C. elegans (8). Hodgkin et al. demonstrated that the genetically amenable nematode C. elegans is ideally suited to identify host factors (12).We examined C. elegans as a pathogenes...

Recently, we reported that Streptococcus pyogenes kills Caenorhabditis elegans by the use of hydrogen peroxide (H 2 O 2 ). Here we show that diverse streptococcal species cause death of C. elegans larvae in proportion to the level of H 2 O 2 produced. H 2 O 2 may mask the effects of other pathogenicity factors of catalase-negative bacteria in the C. elegans infection model.

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Acute rheumatic fever (ARF) is an autoimmune sequela of group A streptococcal infection mostly affecting school-aged children. Recurrent episodes of ARF can result in the development of rheumatic heart disease (RHD). One in 40 indigenous Australians in the Northern Territory is affected by RHD. This disease mostly impacts young people; 45% of those who require heart valve surgery in Australia due to RHD are younger than 25 years old. ARF is characterized by autoimmune attack of the heart; therefore, the presence of the autoantibodies involved could potentially be used to diagnose ARF. To this end, a human heart cDNA library was screened with serum from a patient with ARF, and 12 autoreactive human heart antigens were identified. They include five different IgG heavy chains and a range of tissue-specific cell-signaling proteins, species of which have been implicated in other autoimmune diseases. Preliminary ELISA results show that ARF patients have significantly higher levels of antibodies recognizing the cardiac autoantigens than controls. These antigens are promising candidates for the development of a serological assay for the diagnosis of ARF. The nature of the proteins identified has exciting implications for future research into the pathogenesis of ARF.