Mga is a negative regulator of capsule and phosphorylcholine biosynthesis and influences the virulence of D39.

Global transcriptional regulators are prevalent in gram-positive pathogens. The transcriptional regulators of the Mga/AtxA family regulate target gene expression by directly binding to the promoter regions, that results in the coordinated expression of virulence factors. The gene of strain D39 encodes Mga, which shares sequence similarity with global transcriptional regulators of the Mga/AtxA family. In this study, we demonstrated that Mga regulates the biosynthesis of the capsule and phosphorylcholine, which play key roles in disease severity in infections. Mga directly binds to the and promoters and affects the biosynthesis of the capsule and phosphorylcholine. Mga binds to two specific sites on the promoter of , one of which contains the -35 box of the promoter, with high affinity. Consistently, low-molecular-weight capsule components were observed in the null mutant strain. Moreover, we found that phosphorylcholine content was notably increased in the unencapsulated mutant strain. The null mutant caused more severe systemic disease than the parental strain D39. These findings indicate that the pneumococcal Mga protein can inhibit capsule and phosphorylcholine production, thereby affecting the virulence of