F2F Poster 21st Lancefield International Symposium for Streptococci and Streptococcal Diseases 2022

Adaptation of the Group A Streptococcus – phage A25 virocell to the human host (#107)

Lionel Schiavolin 1 , Valérie Delforge 1 , Pierre R Smeesters 1 2 , Anne Botteaux 1
  1. Molecular Bacteriology Laboratory, Université Libre de Bruxelles, Brussels, Belgium
  2. Paediatric Department, Queen Fabiola Children's University Hospital, Université Libre de Bruxelles, Brussels, Belgium

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Background: Group A Streptococcus (GAS) is responsible for mild to life threatening infections for which antibiotics are the key treatments. Implementation of alternatives like phagotherapy relies on the understanding of the phage–pathogen–host interactions. GAS is known to downregulate fatty acids synthesis (FASII) pathway in presence of human serum, preferentially using fatty acids bound to albumin (HSA+FAs). The predominant FAs in human serum are the unsaturated linoleic (LA) and oleic (OA) acids, and the saturated palmitic (PA) and stearic (SA) acids, with LA>PA>OA>SA. Methods: RNAseq was used to explore the reprogramming of GAS transcriptome during phage infection. We measured the impact of cerulenin (FASII inhibitor), glucose, HSA and FAs on bacterial growth and phage infection by measuring optical density and quantifying PFUs. Results: We found that the phage A25 reprograms up to 27% of the GAS transcriptome, turning the uninfected ribocell into a virocell to sustain phages production. The most downregulated genes belong to the FASII pathway. Since humans are the only reservoir for GAS, we reasoned that the virocell might also have adapted to the human host environment. We found that HSA+FAs, especially HSA+LA and HSA+OA, restore growth of cerulenin-treated ribocell while only glucose has a significant impact on growth yield. Considering the virocell, we found that HSA+FAs, especially HSA+LA, boosts infection compared to glucose suggesting that FAs are a preferred carbon source for the virocell. Conclusions: These data show, for the first time, that a virocell has adapted to the human host environment in a different manner than the corresponding ribocell.