Streptococcal secreted esterase (Sse) is a platelet-activating factor acetylhydrolase that is critical for Group A Streptococcus (GAS) skin invasion and innate immune evasion. There are two Sse variant complexes that share >98% identity within each complex but display about 37% variation between the complexes in amino acid sequences. Sse immunization protects mice against lethal infection and skin invasion in subcutaneous infection with the hypervirulent CovRS mutant strain, MGAS5005. However, it is not known whether Sse immunization provides significant protection against infection of GAS with functional CovRS and whether immunization with Sse of one variant complex provides protection against infection of GAS that produces Sse of another variant complex. This study was designed to address these questions. Mice were immunized with recombinant Sse of M1 GAS (SseM1) and challenged with MGAS5005 (serotype M1, CovS mutant, and Sse of variant complex I), MGAS315 (M3, CovS mutant, and Sse of variant complex I), MGAS2221 (M1, wild-type CovRS, and Sse of variant complex I), and MGAS6180 (M28, wild-type CovRS, and Sse of variant complex II). SseM1 immunization significantly increased survival rates of mice in subcutaneous MGAS5005 and intraperitoneal MGAS6180 challenges and showed consistently higher or longer survival in the other challenges. Immunized mice had smaller skin lesion and higher neutrophil responses in subcutaneous infections and lower GAS burdens in spleen, liver, and kidney in most of the challenge experiments than control mice. SseM1 immunization enhanced proinflammatory responses. These data suggest that Sse immunization has a broad benefit against GAS infections that can vary in extent from strain to strain and that the benefit may be due to the immunization-enhanced proinflammatory responses. In particular, immunization with SseM1 can provide protection against M28 GAS infection even though its Sse and SseM1 have significant variations.

中文翻译：

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用分泌的酯酶进行免疫可保护小鼠免受A组链球菌的多种血清型（M1，M3和M28）的侵害。

链球菌分泌的酯酶（Sse）是一种血小板活化因子乙酰水解酶，对A组链球菌（GAS）皮肤侵袭和先天性免疫逃逸至关重要。有两个Sse变体复合物，每个复合物中的同一性> 98％，但氨基酸序列之间的复合物之间显示约37％的差异。Sse免疫可以保护小鼠免于致命的感染和使用高毒力CovRS突变株MGAS5005的皮下感染。但是，尚不知道Sse免疫能否为功能性CovRS的GAS感染提供显着的保护，以及用一种变体复合物的Sse免疫是否能防止产生另一种变体复合物Sse的GAS感染。本研究旨在解决这些问题。用M1 GAS的重组Sse（SseM1）免疫小鼠，并用MGAS5005（血清型M1，CovS突变体和变体复合体I的Sse），MGAS315（M3，CovS突变体和变体复合体I的Sse），MGAS2221（M1，野生型CovRS和变体复合体I的Sse）和MGAS6180（M28，野生型CovRS和变体复合体II的Sse）。SseM1免疫显着提高了皮下MGAS5005和腹膜内MGAS6180攻击小鼠的存活率，并在其他挑战中始终显示更高或更长的生存期。在大多数挑战实验中，与对照小鼠相比，免疫小鼠在皮下感染中具有较小的皮肤病变和较高的中性粒细胞反应，并且在脾脏，肝脏和肾脏中的GAS负担较低。SseM1免疫增强了促炎反应。这些数据表明，Sse免疫对GAS感染具有广泛的益处，可能因菌株而异，并且受益可能是由于免疫增强的促炎反应。特别是，即使SseM1的Sse和SseM1有显着差异，用SseM1免疫也可以提供针对M28 GAS感染的保护。