Stevioside curbs Streptococcus pneumoniae infection via inhibiting capsule biosynthesis

Area of Science:

• Microbiology
• Drug Discovery
• Biochemistry

Background:

• Streptococcus pneumoniae causes significant childhood and elderly mortality despite vaccines.
• The bacterial capsule is crucial for S. pneumoniae pathogenicity, making it a key drug target.
• Alternative strategies are needed to combat antibiotic-resistant and non-vaccine serotype S. pneumoniae infections.

Purpose of the Study:

• To identify natural compounds that inhibit S. pneumoniae capsule biosynthesis.
• To investigate the mechanism of action of identified inhibitors.
• To evaluate the therapeutic potential of these compounds against S. pneumoniae infections.

Main Methods:

• Identified stevioside as a capsule biosynthesis inhibitor.
• Investigated stevioside's effect on pyruvate metabolism and NAD+/NADH balance.
• Assessed stevioside's impact on bacterial stress resistance, complement resistance, adherence, and phagocytosis in vitro.
• Evaluated stevioside's efficacy in a mouse model of S. pneumoniae infection.

Main Results:

• Stevioside reduced capsular polysaccharide biosynthesis by interfering with pyruvate metabolism.
• The compound disrupted bacterial redox balance and energy generation.
• Stevioside sensitized S. pneumoniae to antibacterial peptides and stress, and attenuated capsule-mediated resistance mechanisms.
• In vivo, stevioside treatment improved survival rates and reduced pathology in infected mice.

Conclusions:

• Stevioside is a promising lead compound for developing novel chemical capsule inhibitors against S. pneumoniae.
• Targeting pyruvate metabolism offers a new strategy for discovering S. pneumoniae capsule inhibitors.
• Stevioside demonstrates therapeutic potential for combating S. pneumoniae infections, including resistant strains.