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

Defining “strain”: Development of an MLST scheme based on surface protein genes for group A streptococci (#181)

John P Noto 1 , Anhphan T Ly 1 , Mosaed Alobaidallah 1 , Lauren Graham 1 , Weihua Huang 2 , John T Fallon 2 , Keith A Jolley 3 , Debra E Bessen 1
  1. Microbiology and Immunology, New York Medical College, Valhalla, New York, USA
  2. Pathology, New York Medical College, Valhalla, New York, USA
  3. University of Oxford, Oxford, UK

Through contributions from >50 investigators, multi-locus sequence typing (MLST) of group A streptococci (GAS) based on 7 core housekeeping loci reveals 921 sequence types (STs) (https://pubmlst.org/spyogenes/; May 2017). ST coupled with emm type provides a rough definition for “clone.” New “clones” of clinical significance often emerge from point mutations or small indels affecting transcriptional regulatory genes. A working definition for “strain” can allow for a deeper evolutionary analysis of the GAS species. Based on genomes of 200 GAS isolates having unique combinations of emm type and genetically-distant STs, plus published data on ~60 additional genomes, sequences were analyzed for genes mapping to the emm- and FCT-regions of the chromosome and encoding proteins with cell wall sorting signals. The data provide a foundation for development of an MLST scheme based on surface protein genes (MLSTsp). Phylogenetic analysis of each surface protein gene allows for assignment of major sequence clusters. The distribution among GAS of sequence clusters for multiple surface protein genes provides evidence for a history of extensive horizontal gene transfer between organisms. Against a background of highly random associations among housekeeping and/or surface protein alleles, genes exhibiting significant nonrandom associations with clinical phenotypes are strong candidates for playing a direct role in that disease. MLSTsp also has the potential to aid in understanding host immune selection and the emergence of new strains via immune escape, and in facilitating rational vaccine design. It is hoped that MLSTsp will become a valuable tool and expanding resource for the GAS field.