title: Human commensals producing a novel antibiotic impair pathogen colonization.
abstract: The vast majority of systemic bacterial infections are caused by facultative, often antibiotic-resistant, pathogens colonizing human body surfaces. Nasal carriage of Staphylococcus aureus predisposes to invasive infection, but the mechanisms that permit or interfere with pathogen colonization are largely unknown. Whereas soil microbes are known to compete by production of antibiotics, such processes have rarely been reported for human microbiota. We show that nasal Staphylococcus lugdunensis strains produce lugdunin, a novel thiazolidine-containing cyclic peptide antibiotic that prohibits colonization by S. aureus, and a rare example of a non-ribosomally synthesized bioactive compound from human-associated bacteria. Lugdunin is bactericidal against major pathogens, effective in animal models, and not prone to causing development of resistance in S. aureus. Notably, human nasal colonization by S. lugdunensis was associated with a significantly reduced S. aureus carriage rate, suggesting that lugdunin or lugdunin-producing commensal bacteria could be valuable for preventing staphylococcal infections. Moreover, human microbiota should be considered as a source for new antibiotics.
authors.affiliation: Interfaculty Institute of Microbiology and Infection Medicine, Infection Biology, University of Tübingen, 72076 Tübingen, Germany.|German Centre for Infection Research (DZIF), Partner Site Tübingen, 72076 Tübingen, Germany.
authors.forename: Alexander
authors.initials: A
authors.lastname: Zipperer
authors.affiliation: Institute of Organic Chemistry, University of Tübingen, 72076 Tübingen, Germany.
authors.forename: Martin C
authors.initials: MC
authors.lastname: Konnerth
authors.affiliation: Interfaculty Institute of Microbiology and Infection Medicine, Infection Biology, University of Tübingen, 72076 Tübingen, Germany.|German Centre for Infection Research (DZIF), Partner Site Tübingen, 72076 Tübingen, Germany.
authors.forename: Claudia
authors.initials: C
authors.lastname: Laux
authors.affiliation: Interfaculty Institute of Microbiology and Infection Medicine, Microbial Bioactive Compounds, University of Tübingen, 72076 Tübingen, Germany.
authors.forename: Anne
authors.initials: A
authors.lastname: Berscheid
authors.affiliation: Interfaculty Institute of Microbiology and Infection Medicine, Infection Biology, University of Tübingen, 72076 Tübingen, Germany.|German Centre for Infection Research (DZIF), Partner Site Tübingen, 72076 Tübingen, Germany.
authors.forename: Daniela
authors.initials: D
authors.lastname: Janek
authors.affiliation: German Centre for Infection Research (DZIF), Partner Site Tübingen, 72076 Tübingen, Germany.|Interfaculty Institute of Microbiology and Infection Medicine, Medical Microbiology, University of Tübingen, 72076 Tübingen, Germany.
authors.forename: Christopher
authors.initials: C
authors.lastname: Weidenmaier
authors.affiliation: Department of Dermatology, Division of Dermatooncology, University of Tübingen, 72076 Tübingen, Germany.
authors.forename: Marc
authors.initials: M
authors.lastname: Burian
authors.affiliation: Institute of Organic Chemistry, University of Tübingen, 72076 Tübingen, Germany.|Interfaculty Institute of Biochemistry, University of Tübingen, 72076 Tübingen, Germany.
authors.forename: Nadine A
authors.initials: NA
authors.lastname: Schilling
authors.affiliation: Interfaculty Institute of Microbiology and Infection Medicine, Infection Biology, University of Tübingen, 72076 Tübingen, Germany.|German Centre for Infection Research (DZIF), Partner Site Tübingen, 72076 Tübingen, Germany.
authors.forename: Christoph
authors.initials: C
authors.lastname: Slavetinsky
authors.affiliation: Interfaculty Institute of Microbiology and Infection Medicine, Medical Microbiology, University of Tübingen, 72076 Tübingen, Germany.
authors.forename: Matthias
authors.initials: M
authors.lastname: Marschal
authors.affiliation: German Centre for Infection Research (DZIF), Partner Site Tübingen, 72076 Tübingen, Germany.|Interfaculty Institute of Microbiology and Infection Medicine, Medical Microbiology, University of Tübingen, 72076 Tübingen, Germany.
authors.forename: Matthias
authors.initials: M
authors.lastname: Willmann
authors.affiliation: Interfaculty Institute of Biochemistry, University of Tübingen, 72076 Tübingen, Germany.
authors.forename: Hubert
authors.initials: H
authors.lastname: Kalbacher
authors.affiliation: Department of Dermatology, Division of Dermatooncology, University of Tübingen, 72076 Tübingen, Germany.
authors.forename: Birgit
authors.initials: B
authors.lastname: Schittek
authors.affiliation: German Centre for Infection Research (DZIF), Partner Site Tübingen, 72076 Tübingen, Germany.|Interfaculty Institute of Microbiology and Infection Medicine, Microbial Bioactive Compounds, University of Tübingen, 72076 Tübingen, Germany.
authors.forename: Heike
authors.initials: H
authors.lastname: Brötz-Oesterhelt
authors.affiliation: Institute of Organic Chemistry, University of Tübingen, 72076 Tübingen, Germany.
authors.forename: Stephanie
authors.initials: S
authors.lastname: Grond
authors.affiliation: Interfaculty Institute of Microbiology and Infection Medicine, Infection Biology, University of Tübingen, 72076 Tübingen, Germany.|German Centre for Infection Research (DZIF), Partner Site Tübingen, 72076 Tübingen, Germany.
authors.forename: Andreas
authors.initials: A
authors.lastname: Peschel
authors.affiliation: Interfaculty Institute of Microbiology and Infection Medicine, Infection Biology, University of Tübingen, 72076 Tübingen, Germany.|German Centre for Infection Research (DZIF), Partner Site Tübingen, 72076 Tübingen, Germany.
authors.forename: Bernhard
authors.initials: B
authors.lastname: Krismer
mesh_terms: D000818:Animals; D000900:Anti-Bacterial Agents / Q000096:biosynthesis / Q000378:metabolism*; D002353:Carrier State / Q000382:microbiology; D004195:Disease Models, Animal; D004352:Drug Resistance, Microbial; D005260:Female; D006801:Humans; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008826:Microbial Sensitivity Tests; D064307:Microbiota / Q000502:physiology; D009666:Nose / Q000382:microbiology; D010456:Peptides, Cyclic / Q000378:metabolism*; D016205:Sigmodontinae; D013203:Staphylococcal Infections / Q000188:drug therapy / Q000382:microbiology* / Q000517:prevention & control*; D013211:Staphylococcus aureus / Q000254:growth & development* / Q000472:pathogenicity; D057787:Staphylococcus lugdunensis / Q000378:metabolism*; D013559:Symbiosis; D053778:Thiazolidines / Q000378:metabolism*
chemical_list: D000900:Anti-Bacterial Agents; D010456:Peptides, Cyclic; D053778:Thiazolidines; C000609985:lugdunin