Functional and Transcriptome Analysis of

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.