Human tonsils are commonly the primary site of Streptococcus pyogenes infection, however limited knowledge of host:pathogen interactions exists at this site due to lack of appropriate infection models. We have used a primary tonsil keratinocyte infection model in 2D, to study S. pyogenes adherence and invasion. We have also developed a novel tissue-engineered 3D model of human tonsil infection that better reflects the complex nature of a native human tonsil.
We focused our study on the new acapsular/high toxin variant of emm89, now dominant in most high income countries, to determine the role of the capsule and the toxins NADase and Streptolysin O in this setting. We also assessed the ability of non-invasive clinical isolates belonging to 18 of the most common S. pyogenes emm-types, and for which we have whole genome sequence data. Some of these leading genotypes are also acapsular with/without high toxin expression.
New acapsular/high toxin variant emm89 isolates had greater adhesion and invasion capacity with our different tonsil infection models, compared to encapsulated/low toxin emm89 isolates. New variant emm89 isolates also demonstrated prolonged survival within these models in the presence of antibiotics. Isolates belonging to other leading genotypes had varying abilities to adhere and invade tonsil infection models. In some cases, this was related to capsule expression.
Work is on-going to delineate the role of various virulence factors in human tonsil infection as it is likely to be the driver behind the emergence of successful new variants that go on to be dominant in the population.