Effect of the polysachharide capsule on Streptococcus pneumoniae resistance to cationic antimicrobial peptides

• Grant number: 24/03296-2
• Support Opportunities: Scholarships in Brazil - Scientific Initiation
• Start date: July 01, 2024
• End date: December 31, 2025
• Field of knowledge: Biological Sciences - Microbiology - Applied Microbiology
• Principal Investigator: Michelle Darrieux Sampaio Bertoncini
• Grantee: Maria Eduarda Pereira Mendes
• Host Institution: Universidade São Francisco (USF). Campus Bragança Paulista. Bragança Paulista , SP, Brazil

Abstract

Streptococcus pneumoniae (pneumococcus) is a pathogen of great clinical interest, responsible for high mortality worldwide. It causes diseases of varying severity, ranging from localized conditions such as middle ear infection and conjunctivitis to more serious forms such as pneumonia, meningitis, and sepsis. It mainly affects children, the elderly, and immunocompromised individuals, contributing to high mortality rates. The polysaccharide capsule (CPS) is an important virulence factor of pneumococcus; it acts to protect against phagocytosis and the action of antimicrobial peptides (AMPs) on the bacterium. Two important human AMPs are HNP-I and LL-37, which exhibit antimicrobial and immunomodulatory action. It is known that pneumococcus is partially resistant to the action of AMPs; however, the mechanisms responsible for this resistance are not fully understood. This project aims to evaluate the role of the polysaccharide capsule in the action of HNP-1 and LL-37 on pneumococcus. The inhibitory concentrations of AMPs on pneumococcus will be determined using an in vitro bactericidal assay. Pneumococci of different capsular serotypes will be evaluated for resistance to treatment with AMPs. Wild-type and capsule non-producing mutants will be treated with the peptides, and survival will be compared to untreated control. Subsequently, bacteria will be treated with AMPs in the presence or absence of anticapsular antibodies and purified capsular polysaccharides. Finally, the effects of capsule variation on AMP action will be assessed by comparing capsule-switch mutants of pneumococci. Together, the data from this work will contribute to elucidating the role of variations in the polysaccharide capsule in the action of defensins and cathelicidins on pneumococcus - an important defense mechanism that can be exploited to combat this pathogen.