Hypervirulent Group AStreptococcusof Genotypeemm3 Invades the Vascular System in Pulmonary Infection of Mice
ABSTRACTNatural mutations of the two-component regulatory system CovRS are frequently associated with invasive group AStreptococcus(GAS) isolates and lead to the enhancement of virulence gene expression, innate immune evasion, systemic dissemination, and virulence. How CovRS mutations enhance systemic dissemination is not well understood. A hypervirulent GAS isolate of theemm3 genotype, MGAS315, was characterized using a mouse model of pulmonary infection to understand systemic dissemination. This strain has a G1370T mutation in the sensor kinasecovSgene of CovRS. Intratracheal inoculation of MGAS315 led to the lung infection that displayed extensive Gram staining at the alveolar ducts, alveoli, and peribronchovascular and perivascular interstitium. The correction of thecovSmutation did not alter the infection at the alveolar ducts and alveoli but prevented GAS invasion of the peribronchovascular and perivascular interstitium. Furthermore, thecovSmutation allowed MGAS315 to disrupt and degrade the smooth muscle and endothelial layers of the blood vessels, directly contributing to systemic dissemination. It is concluded that hypervirulentemm3 GAScovSmutants can invade the perivascular interstitium and directly attack the vascular system for systemic dissemination.