Direct interaction between pathogens and host cells often is a prerequisite for colonization, infection and dissemination.Regulated production of capsular polysaccharide (CPS),which is made of hyaluronic acid, is essential for the pathogenicity of Streptococcus equi subsp.zooepidemicus.Here, we constructed a CPS-deleted mutant and analyzed it along with the parental wild-type strain in attachment and invasion of mammalian epithelial and endothelial cell lines.The CPS-deleted mutant exhibited significant increase in adherence and invasion by several orders of magnitude compared with the wild-type strain through quantitative analysis and electron microscopy observation.After the wild-type strain was recovered from invaded cells, its morphology was analyzed by visual methods and scanning electron microscopy, which revealed that its capsule was almost completely absent.Capsule measurements showed a similar result in which CPS production was nearly attenuated to the same extent as in the CPS-deleted mutant.qPCR assays revealed a marked reduction in the transcriptional levels of the CPS biosynthesis genes, has operon.Moreover, the repression in capsular production was stable inheritance.Our findings indicate that SEZ is a facultative intracellular bacterium, capsule attenuation in SEZ contributes to attachment and invasion in interactions with host cells, and the active regulation of capsule breakdown is controlled by SEZ during internalization.