Secreted antigen A (SagA) (SagA)

Secreted antigen A (SagA) is a peptidoglycan hydrolase primarily identified in Enterococcus faecium that has emerged as a significant modulator of host immunity (Pedicord et al., 2016, Science). The protein functions as an N-acetylmuramoyl-L-alanine amidase, cleaving the bacterial cell wall to release bioactive muropeptides that serve as ligands for the host intracellular receptor NOD2 (Griffin et al., 2021, Science). This interaction triggers a signaling cascade that enhances the recruitment and effector function of CD8+ T cells, particularly within the tumor microenvironment (Kim et al., 2019, Science). Consequently, SagA has been shown to significantly improve the therapeutic efficacy of immune checkpoint inhibitors, such as PD-1 and PD-L1 blockers, in preclinical models. Current biotech efforts are focused on utilizing SagA-expressing engineered probiotics or purified SagA muropeptides as adjuvant therapies to overcome resistance to immunotherapy in cancer patients. However, potential safety concerns include the risk of over-activating the innate immune system or inducing inflammatory conditions in susceptible individuals.

Other names

Peptidoglycan hydrolase SagAN-acetylmuramoyl-L-alanine amidase SagAp54 proteinMajor secreted protein SagA

SagA is an N-acetylmuramoyl-L-alanine amidase that cleaves bacterial peptidoglycan to release muropeptides; these fragments activate the intracellular receptor NOD2, which promotes the secretion of cytokines and enhances the anti-tumor activity of T cells.