220D-F2 from Rubus ulmifolius kills Streptococcus pneumoniae planktonic cells and pneumococcal biofilms.
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.
Hubert Department of Global Health, Rollins School of Public Health, Atlanta, Georgia, United States of America.
Sharmila J
SJ
Talekar
Hubert Department of Global Health, Rollins School of Public Health, Atlanta, Georgia, United States of America.
Sopio
S
Chochua
Center for the Study of Human Health, Emory College of Arts and Sciences, Atlanta, Georgia, United States of America.
Katie
K
Nelson
Hubert Department of Global Health, Rollins School of Public Health, Atlanta, Georgia, United States of America.
Keith P
KP
Klugman
Center for the Study of Human Health, Emory College of Arts and Sciences, Atlanta, Georgia, United States of America; Department of Dermatology, School of Medicine, Emory University, Atlanta, Georgia, United States of America.
Cassandra L
CL
Quave
Hubert Department of Global Health, Rollins School of Public Health, Atlanta, Georgia, United States of America.
Jorge E
JE
Vidal
D000900:Anti-Bacterial Agents / Q000032:analysis / Q000494:pharmacology*; D018441:Biofilms / Q000187:drug effects*; D019149:Bioreactors / Q000382:microbiology; D002460:Cell Line; D017931:DNA Primers / Q000235:genetics; D004305:Dose-Response Relationship, Drug; D004610:Ellagic Acid / Q000032:analysis / Q000494:pharmacology*; D005453:Fluorescence; D006801:Humans; D008826:Microbial Sensitivity Tests; D009305:Nasopharynx / Q000382:microbiology; D010936:Plant Extracts / Q000032:analysis / Q000494:pharmacology*; D065856:Rubus / Q000737:chemistry*; D013296:Streptococcus pneumoniae / Q000187:drug effects*
D000900:Anti-Bacterial Agents; D017931:DNA Primers; D010936:Plant Extracts; D004610:Ellagic Acid