Abstract
Streptococcus pneumoniae (pneumococcus) forms organized biofilms to persist in the human nasopharynx. This persistence allows the pneumococcus to produce severe diseases such as pneumonia, otitis media, bacteremia and meningitis that kill nearly a million children every year. While bacteremia and meningitis are mediated by planktonic pneumococci, biofilm structures are present during pneumonia and otitis media. The global emergence of S. pneumoniae strains resistant to most commonly prescribed antibiotics warrants further discovery of alternative therapeutics. The present study assessed the antimicrobial potential of a plant extract, 220D-F2, rich in ellagic acid, and ellagic acid derivatives, against S. pneumoniae planktonic cells and biofilm structures. Our studies first demonstrate that, when inoculated together with planktonic cultures, 220D-F2 inhibited the formation of pneumococcal biofilms in a dose-dependent manner. As measured by bacterial counts and a LIVE/DEAD bacterial viability assay, 100 and 200 µg/ml of 220D-F2 had significant bactericidal activity against pneumococcal planktonic cultures as early as 3 h post-inoculation. Quantitative MIC’s, whether quantified by qPCR or dilution and plating, showed that 80 µg/ml of 220D-F2 completely eradicated overnight cultures of planktonic pneumococci, including antibiotic resistant strains. When preformed pneumococcal biofilms were challenged with 220D-F2, it significantly reduced the population of biofilms 3 h post-inoculation. Minimum biofilm inhibitory concentration (MBIC)50 was obtained incubating biofilms with 100 µg/ml of 220D-F2 for 3 h and 6 h of incubation. 220D-F2 also significantly reduced the population of pneumococcal biofilms formed on human pharyngeal cells. Our results demonstrate potential therapeutic applications of 220D-F2 to both kill planktonic pneumococcal cells and disrupt pneumococcal biofilms.
Highlights
Streptococcus pneumoniae is an important human pathogen associated with high morbidity and mortality [1]
220D-F2 Inhibits Formation of Pneumococcal Biofilms We and others have previously demonstrated that biofilms made by invasive S. pneumoniae strain D39 are completely formed between 8 to 10 h post-inoculation
Our results demonstrate dose-dependent inhibition of formation of pneumococcal biofilms treated with 220D-F2 but DMSO did not have an apparent inhibitory effect on the formation of biofilms
Summary
Streptococcus pneumoniae (pneumococcus) is an important human pathogen associated with high morbidity and mortality [1]. Biofilms are structured communities of bacterial cells enclosed in a self-produced polymeric matrix composed of polysaccharides, proteins and nucleic acids that is adherent to inert or living surfaces [11] In comparison to their planktonic counterparts (108 CFU/ml), biofilm bacteria reach a much higher density (1011 CFU/ml) which may impact the pharmacodynamics of antibiotics [12]. Pneumococci embedded in these biofilms can migrate to other anatomic sites to cause severe biofilm-associated diseases such as pneumonia, and otitis media, [13,14,15]. From the lungs of patients with pneumococcal pneumonia or the ear cavity when causing otitis media, planktonic pneumococci can disperse from the biofilm structure and invade sterile sites such as the blood stream or brain, to cause lethal bacteremia or meningitis, respectively [16,17,18]
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