屎肠球菌是人类中的一种微生物群,可以调节宿主免疫力(Griffin和Hang,2022),但也获得了抗生素耐药性,是医院相关感染的主要原因(VanTyne和Gilmore,2014).值得注意的是,不同的屎肠球菌菌株产生SagA,一种高度保守的肽聚糖水解酶,足以促进肠道免疫(Rangan等人。,2016;Pedicord等人。,2016年;Kim等人。,2019年)和免疫检查点抑制剂抗肿瘤活性(Griffin等人。,2021)。然而,SagA在屎肠球菌中的功能未知。这里,我们报告说,由于肽聚糖裂解和细胞分离缺陷,sagA的缺失会损害屎肠球菌的生长,并导致肠球菌膨胀和聚集。此外,ΔsagA显示抗生素敏感性增加,产生较低水平的活性莫罗肽,显示肽聚糖模式识别受体NOD2的激活降低,并且未能促进癌症免疫疗法。重要的是,基于质粒的SagA表达,但不是它的催化失活突变体,恢复了ΔsagA生长,生产活性muropoptimes,和NOD2激活。Saga是,因此,对屎肠球菌生长至关重要,抗应力,和宿主免疫的激活。
Enterococcus faecium is a microbiota species in humans that can modulate host immunity (Griffin and Hang, 2022), but has also acquired antibiotic resistance and is a major cause of hospital-associated infections (Van Tyne and Gilmore, 2014). Notably, diverse strains of E. faecium produce SagA, a highly conserved peptidoglycan hydrolase that is sufficient to promote intestinal immunity (Rangan et al., 2016; Pedicord et al., 2016; Kim et al., 2019) and immune checkpoint inhibitor antitumor activity (Griffin et al., 2021). However, the functions of SagA in E. faecium were unknown. Here, we report that deletion of sagA impaired E. faecium growth and resulted in bulged and clustered enterococci due to defective peptidoglycan cleavage and cell separation. Moreover, ΔsagA showed increased antibiotic sensitivity, yielded lower levels of active muropeptides, displayed reduced activation of the peptidoglycan pattern-recognition receptor NOD2, and failed to promote cancer immunotherapy. Importantly, the plasmid-based expression of SagA, but not its catalytically inactive mutant, restored ΔsagA growth, production of active muropeptides, and NOD2 activation. SagA is, therefore, essential for E. faecium growth, stress resistance, and activation of host immunity.