title: Precision-guided antimicrobial peptide as a targeted modulator of human microbial ecology.
abstract: 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.
authors.affiliation: School of Dentistry, University of California, Los Angeles, CA 90095;
authors.forename: Lihong
authors.initials: L
authors.lastname: Guo
authors.affiliation: Department of Periodontics, University of Washington, Seattle, WA 98195; Microbial and Environmental Genomics, J. Craig Venter Institute, La Jolla, CA 92037;
authors.forename: Jeffrey S
authors.initials: JS
authors.lastname: McLean
authors.affiliation: Microbial and Environmental Genomics, J. Craig Venter Institute, La Jolla, CA 92037;
authors.forename: Youngik
authors.initials: Y
authors.lastname: Yang
authors.affiliation: C3 Jian, Inc., Marina del Rey, CA 90292.
authors.forename: Randal
authors.initials: R
authors.lastname: Eckert
authors.affiliation: C3 Jian, Inc., Marina del Rey, CA 90292.
authors.forename: Christopher W
authors.initials: CW
authors.lastname: Kaplan
authors.affiliation: C3 Jian, Inc., Marina del Rey, CA 90292.
authors.forename: Pierre
authors.initials: P
authors.lastname: Kyme
authors.affiliation: C3 Jian, Inc., Marina del Rey, CA 90292.
authors.forename: Omid
authors.initials: O
authors.lastname: Sheikh
authors.affiliation: C3 Jian, Inc., Marina del Rey, CA 90292.
authors.forename: Brian
authors.initials: B
authors.lastname: Varnum
authors.affiliation: School of Dentistry, University of California, Los Angeles, CA 90095;
authors.forename: Renate
authors.initials: R
authors.lastname: Lux
authors.affiliation: School of Dentistry, University of California, Los Angeles, CA 90095; C3 Jian, Inc., Marina del Rey, CA 90292 wshi@dentistry.ucla.edu xhe@g.ucla.edu.
authors.forename: Wenyuan
authors.initials: W
authors.lastname: Shi
authors.affiliation: School of Dentistry, University of California, Los Angeles, CA 90095; wshi@dentistry.ucla.edu xhe@g.ucla.edu.
authors.forename: Xuesong
authors.initials: X
authors.lastname: He
mesh_terms: D000328:Adult; D000900:Anti-Bacterial Agents / Q000494:pharmacology; D023181:Antimicrobial Cationic Peptides / Q000494:pharmacology*; D018441:Biofilms / Q000187:drug effects / Q000254:growth & development; D003731:Dental Caries / Q000382:microbiology; D006801:Humans; D008826:Microbial Sensitivity Tests; D064307:Microbiota / Q000187:drug effects*; D009055:Mouth / Q000382:microbiology; D012463:Saliva / Q000382:microbiology; D013295:Streptococcus mutans / Q000187:drug effects* / Q000472:pathogenicity / Q000502:physiology*
chemical_list: D000900:Anti-Bacterial Agents; D023181:Antimicrobial Cationic Peptides
keywords: dental caries; human microbiome; oral microbiota; targeted antimicrobial