Affiliation:
1. Department of Microbiology and Immunology, Montana State University, Bozeman, Montana, USA
Abstract
ABSTRACT
Natural mutations of the two-component regulatory system CovRS are frequently associated with invasive group A
Streptococcus
(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 the
emm
3 genotype, MGAS315, was characterized using a mouse model of pulmonary infection to understand systemic dissemination. This strain has a G1370T mutation in the sensor kinase
covS
gene 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 the
covS
mutation did not alter the infection at the alveolar ducts and alveoli but prevented GAS invasion of the peribronchovascular and perivascular interstitium. Furthermore, the
covS
mutation 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 hypervirulent
emm
3 GAS
covS
mutants can invade the perivascular interstitium and directly attack the vascular system for systemic dissemination.
Funder
National Institiutes of Health
HHS | National Institutes of Health
Publisher
American Society for Microbiology
Subject
Infectious Diseases,Immunology,Microbiology,Parasitology
Cited by
5 articles.
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