A naturally occurring point mutation in the rocA gene of Streptococcus pyogenes confers the highly virulent phenotype

Introduction: Mucoid (MTB313) and nonmucoid (MTB314) strains of group A streptococcus (GAS) emm (antiphagocytic M protein) type 1 were simultaneously isolated from a single patient suffering from streptococcal meningitis. In a CD46-expressing transgenic (CD46 Tg) mouse model of subcutaneous infection into both hind footpads with MTB313 or MTB314, MTB313 showed considerably higher virulence than MTB314. Methods: The comparative genomic analysis based on the whole-genome sequencing revealed that MTB313 possessed an amber codon within rocA (sensory transduction protein kinase), but MTB314 did not carry this stop codon. Thereafter, MAT101 was generated from MTB313 by introducing pRocA, which contained the full-length rocA from MTB314, into the cloning plasmid pLZ12-Km2. MAT100 was also generated by introducing pLZ12-Km2 into MTB313. Results: Although MTB313 and MAT100 showed large quantities of cell-associated hyaluronic acid (HA) in the culture pellets, MTB314 and MAT101 showed small quantities of HA production. Finally, higher mortalities were observed in the MTB313or MAT100-infected CD46 Tg mice than the MTB314or MAT101-infected CD46 Tg mice. Conclusions: These data indicate the possibility that a spontaneous point mutation in the rocA gene led to the highly virulent phenotype of M1 GAS. 0 2020 Japanese Society of Chemotherapy and The Japanese Association for Infectious Diseases. Published by Elsevier Ltd. All rights reserved.

Automated summary

The study indicates that a spontaneous point mutation in the rocA gene may have led to the highly virulent phenotype of M1 GAS. Infection with MTB313 or MAT100 resulted in higher mortalities in CD46 Tg mice, while MTB314 or MAT101 showed lower hyaluronic acid (HA) production.