PotD contributes to Streptococcus suis-induced blood–brain barrier disruption by regulating arcA transcription

TL;DR

This study shows that the PotD protein in Streptococcus suis helps disrupt the blood-brain barrier by regulating another protein, arcA, which contributes to the bacteria's harmful effects.

Contribution

The study identifies PotD as a key virulence factor in Streptococcus suis that mediates blood-brain barrier disruption through regulation of arcA transcription.

Findings

Deletion of potD reduced bacterial load and improved mouse survival, indicating its role in pathogenicity.

PotD disrupts the blood-brain barrier by downregulating tight junction proteins ZO-1 and Occludin.

PotD interacts with ADI (encoded by arcA) and mediates arcA transcription, contributing to BBB disruption.

Abstract

The ABC transporter substrate-binding protein PotD plays an important role in bacteria for polyamine uptake, but its role in the pathogenicity of Streptococcus suis (S. suis) in the host is still unknown. Our study investigated the mechanism by which PotD mediates S. suis pathogenicity, especially S. suis-induced blood–brain barrier (BBB) disruption. The results showed that ΔpotD mutant significantly reduced biofilm formation and bacterial load in different tissues, including brain, blood, liver, and lung. Importantly, knockout of potD significantly improved mouse survival rate, indicating that PotD is involved in S. suis pathogenicity. The deletion of potD significantly reversed the reduction of tight junction proteins ZO-1 and Occludin in mouse brain and human cerebral microvascular endothelial cell line D3 (hCMEC/D3), and attenuated BBB disruption via Evans blue (EB) staining assay. Notably, recombinant PotD protein exhibited the disruption of BBB by downregulating ZO-1 and Occludin in hCMEC/D3 cells, demonstrating that PotD contributes to S. suis-induced BBB disruption. Furthermore, mass spectrometry analysis and pulldown assay revealed that PotD interacted with arginine deiminase (ADI) encoded by arcA and mediated arcA transcription. In addition, ΔarcA mutant attenuated BBB disruption, and recombinant ADI induced BBB disruption by downregulating ZO-1 and Occludin in hCMEC/D3 cells. Our study reveals the destructive role of the virulence factors potD and arcA of S. suis on the BBB and provides new insights into S. suis pathogenicity.

The online version contains supplementary material available at 10.1186/s13567-025-01676-9.

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