14 January 2003

by Colin A. Michie colinm@easynet.co.uk
 

Recent analyses of bacterial gene expression during streptococcal infections have suggested that specific patterns of virulence might lead to specific clinical syndromes. For example, invasive throat strains of group A streptococci can cause damage to heart joints, the central nervous system and the skin in a condition known as acute rheumatic fever. Examination of an M18 Streptococcus pyogenes associated with acute rheumatic fever found that it expressed distinct genes: speL and speM. These are bacteriophage genes that encode superantigens. Both molecules activate the human T-cell repertoire in a Vbeta-skewed fashion, identifying them as superantigens, and antibodies to them have been identified in rheumatic fever patients, suggesting that they are present during infection. The speL superantigen has homology with other streptococcal superantigens, including speC and the potent SmeZ-2, and has been implicated in streptococcal toxic-shock syndrome in Japan. This identification of a particular ‘rheumatogenic’ strain of Streptococcus might account for recent outbreaks of acute rheumatic fever in developed countries, where this disease has become less common over the past century.

Several crucial questions should now alter the focus from microorganism to host. Why might activation of a specific pattern of T lymphocytes be associated with the clinical syndrome of acute rheumatic fever? How do these activated T cells play a role in producing signs to fit the clinical Jones criteria? How do they cause damage to connective tissue collagen to produce the Ashcoff bodies that are characteristic of acute rheumatic fever? Finally, could differential production of superantigens account for the wide clinical variation in acute rheumatic fever, or even its overlap with other conditions? Links between superantigens and autoimmune pathologies have been described in a range of animal models, and it is possible that these new molecules will help to uncover an important mechanism in patients.

The benefits of such phage-derived molecules to streptococci have not yet been defined. However, it is clear that they can readily move horizontally through bacterial populations, altering virulence patterns. With human traffic becoming increasingly global, rising antibiotic resistance and changes in climatic cycles, the potential for more dramatic human streptococcal disease can only be increased by these superantigens. The design of rapid diagnoses and appropriate treatments should become a high priority.