Abstract
The emergence of antibiotic-resistant pathogenic bacteria is a healthcare problem worldwide. We evaluated the antimicrobial activity of rhodomyrtone, an acylphloroglucinol present in Rhodomyrtus tomentosa leaves, against the human Gram-positive pathogen Streptococcus pneumoniae. The compound exhibited pronounced anti-pneumococcal activity against a broad collection of clinical isolates. We studied the effects at the molecular level by integrated proteomic and metabolomic analysis. The results revealed alterations in enzymes and metabolites involved in several metabolic pathways including amino acid biosynthesis, nucleic acid biosynthesis, glucid, and lipid metabolism. Notably, the levels of two enzymes (glycosyltransferase and UTP-glucose-1-phosphate uridylyltransferase) and three metabolites (UDP-glucose, UDP-glucuronic acid and UDP-N-acetyl-D-galactosamine) participating in the synthesis of the pneumococcal capsule clearly diminished in the bacterial cells exposed to rhodomyrtone. Rhodomyrtone-treated pneumococci significantly possessed less amount of capsule, as measured by a colorimetric assay and visualized by electron microscopy. These findings reveal the utility of combining proteomic and metabolomic analyses to provide insight into phenotypic features of S. pneumoniae treated with this potential novel antibiotic. This can lead to an alternative antibiotic for the treatment of S. pneumoniae infections, because of the growing concern regarding antimicrobial resistance.
Highlights
Streptococcus pneumoniae is a Gram-positive bacterium that colonizes in the human upper respiratory tract
The aim of this work was to study the antibacterial effect of rhodomyrtone on S. pneumoniae, and the changes induced at molecular level using proteomics and metabolomics
We tested the antibacterial activity of Rhodomyrtus tomentosa ethanol extract, purified rhodomyrtone, and synthetic rhodomyrtone against a collection of pediatric S. pneumoniae clinical isolates (Table S1) by assaying the minimal inhibitory and bactericidal concentrations
Summary
Streptococcus pneumoniae (the pneumococcus) is a Gram-positive bacterium that colonizes in the human upper respiratory tract Under appropriate conditions, this microorganism may become a leading cause of serious diseases. We have studied the response of two reference pneumococcal strains including the virulent, encapsulated strain TIGR4 and the non-encapsulated avirulent strain R6 in the presence of the purified compound, using proteomics and metabolomics. This may help to provide insight into the mechanism of action of the substance, to be used as a possible antibiotic for the treatment of S. pneumoniae infections. Our work reveals the utility of multi-omic approaches to contribute to the comprehension of the effects of drugs to treat infectious diseases
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