Precision-guided antimicrobial peptide as a targeted modulator of human microbial ecology

• Published in: Proceedings of the National Academy of Sciences - PNAS Vol. 112; no. 24; pp. 7569 - 7574
• Main Authors: Guo, Lihong, Jeffrey S. McLean, Youngik Yang, Randal Eckert, Christopher W. Kaplan, Pierre Kyme, Omid Sheikh, Brian Varnum, Renate Lux, Wenyuan Shi, Xuesong He
• Format: Journal Article
• Language: English
• Published: United States National Academy of Sciences 16.06.2015; National Acad Sciences
• Subjects: Adult; Anti-Bacterial Agents - pharmacology; anti-infective agents; Antimicrobial agents; Antimicrobial Cationic Peptides - pharmacology; antimicrobial peptides; Biofilms - drug effects; Biofilms - growth & development; Biological Sciences; Dental care; Dental caries; Dental Caries - microbiology; Ecological function; human microbiome; Humans; microbial communities; Microbial Sensitivity Tests; microbiome; Microbiota - drug effects; Mouth - microbiology; oral microbiota; Peptides; Saliva - microbiology; Streptococcus infections; Streptococcus mutans; Streptococcus mutans - drug effects; Streptococcus mutans - pathogenicity; Streptococcus mutans - physiology; targeted antimicrobial; dental caries; human microbiome; oral microbiota; targeted antimicrobial
• ISSN: 0027-8424; 1091-6490; 1091-6490
• DOI: 10.1073/pnas.1506207112

One major challenge to studying human microbiome and its associated diseases is the lack of effective tools to achieve targeted modulation of individual species and study its ecological function within multispecies communities. Here, we show that C16G2, a specifically targeted antimicrobial peptide, was able to selectively kill cariogenic pathogen Streptococcus mutans with high efficacy within a human saliva-derived in vitro oral multispecies community. Importantly, a significant shift in the overall microbial structure of the C16G2-treated community was revealed after a 24-h recovery period: several bacterial species with metabolic dependency or physical interactions with S. mutans suffered drastic reduction in their abundance, whereas S. mutans ’ natural competitors, including health-associated Streptococci, became dominant. This study demonstrates the use of targeted antimicrobials to modulate the microbiome structure allowing insights into the key community role of specific bacterial species and also indicates the therapeutic potential of C16G2 to achieve a healthy oral microbiome. Significance The lack of effective tools to modulate individual species within a complex microbial community poses a major barrier to studying human microbiome and its associated diseases. We showed targeted removal of human cariogenic Streptococcus mutans within an in vitro oral multispecies community using a high-efficacy antimicrobial peptide—C16G2—as well as drastic reconstruction of the microbial structure following treatment. The findings suggest the potential of using targeted antimicrobials to modulate microbiome and study the ecological function of specific bacterial species.