Mannose receptor-derived peptides neutralize pore-forming toxins and reduce inflammation and development of pneumococcal disease

ABSTRACT: Cholesterol-dependent cytolysins (CDCs) are essential virulence factors for human pathogens like Streptococcus pneumoniae (pneumolysin, PLY), Streptococcus pyogenes (streptolysin O, SLO), and Listeria monocytogenes (Listeriolysin, LLO). Recently, we identified that PLY interacts with the mannose receptor (MRC-1) on specific immune cells thereby evoking anti-inflammatory responses. Here, we identified the interaction sites between MRC-1 and CDCs using computational docking. We designed peptides from the CTLD4 domain of MRC-1 that binds to PLY, SLO and LLO, respectively. In vitro, the peptides blocked CDC-induced cytolysis and inflammatory cytokine production by human macrophages, and reduced PLY-induced damage of the epithelial barrier integrity and blocked bacterial invasion into the epith

SUBMITTER: Dr. Karthik Subramanian 

PROVIDER: S-SCDT-EMM-2020-12695 | biostudies-other |

REPOSITORIES: biostudies-other