Esterases are broadly expressed in bacteria, but much remains unknown about their pathogenic effect. In previous studies, we focused on an
esterase secreted by Streptococcus pyogenes (group A Streptococcus, GAS). Streptococcal secreted
esterase (Sse) can hydrolyze the sn−2
ester bonds of platelet−activating factor (PAF), converting it to an inactive form that inhibits neutrophil chemotaxis to the
infection sites. However, as a virulent
protein, Sse probably participates in GAS pathogenesis far beyond chemotaxis inhibition. In this study, we generated the sse gene knockout strain (Δsse) from the parent strain MGAS5005 (hypervirulent M1T1 serotype) and compared the difference in phenotypes. Absence of Sse was related to weakened skin invasion in a murine
infection model, and significantly reduced GAS epithelial adherence, invasion, and intracellular survival. Reduced virulence of the Δsse mutant strain was explored through transcriptome analysis, revealing a striking reduction in the abundance of invasive
virulence factors including M
protein, SIC,
ScpA, and SclA. Besides the influence on the virulence, Sse also affected
carbohydrate,
amino acid,
pyrimidine, and
purine metabolism pathways. By elucidating Sse−mediated pathogenic process, the study will contribute to the development of new therapeutic agents that target bacterial
esterases to control clinical GAS
infections.