Poster Presentation 20th Lancefield International Symposium on Streptococci and Streptococcal Diseases 2017

Early Extracellular Lymphatic Dissemination of Streptococcus pyogenes: Prevalence and Implications for Pathogenesis (#200)

Matthew K Siggins 1 , Nicola N Lynskey 1 , Claire E Turner 2 , Lucy Lamb 1 , David G Jackson 3 , Shiranee Sriskandan 1
  1. Infectious Diseases and Immunity, Imperial College London, London, UK
  2. Florey Institute, University of Sheffield, Sheffield, UK
  3. Weatherall Institute of Molecular Medicine, University of Oxford, Oxford, UK


We recently described lymphatic tropism in hyper-encapsulated emm18 S. pyogenes that requires interaction of capsular hyaluronan with the receptor LYVE-1. The utilisation of this lymphatic infection route among more clinically-prevalent S. pyogenes strains, as well as its importance in other manifestations of streptococcal disease are unexplored. We determined the frequency of lymphatic dissemination of a range of clinically relevant S. pyogenes strains and assessed host cell involvement. Furthermore, we characterised the kinetics and dynamics of the process to explore the interplay with systemic infection.



Lymphatic dissemination of S. pyogenes isolates was measured by plating CFU from organs following i.m infection of BALB/c and FVB/n mice. LYVE-1 blocking antibodies were used to obstruct lymphatic tropism.



Emm1, Emm3, and Emm89 S. pyogenes reached the draining lymph node within 30 minutes following deep tissue infection. Gentamicin protection assays demonstrated that the majority (>99%) of S. pyogenes in the lymph node were extracellular. Flow cytometric analysis showed that bacteria at the infection site were not associated with host leukocytes. Isogenic emm1 isolates revealed that both covR mutation and upregulated capsule expression increased bacterial load in the draining lymph node and systemic organs, whereas capsule deletion reduced this. Blocking LYVE-1 prior to infection reduced bacterial load in the draining lymph node but increased systemic bacterial load.



Lymphatic dissemination of S. pyogenes is a phenomenon with pertinence beyond hyper-encapsulated strains. A link between uptake and retention of S. pyogenes in the lymphatics and systemic infection spread warrants continued investigation.