Did You Know?
Individuals colonized with Staphylococcus lugdunensis—the natural producer of lugdunin—are six times less likely to carry Staphylococcus aureus in their nasal microbiome, suggesting that the commensal’s antibiotic production naturally limits pathobiont colonization.
Lugdunin
Researched by:
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Karen Pendergrass
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Karen Pendergrass
Karen Pendergrass is a microbiome researcher specializing in microbiome-targeted interventions (MBTIs). She systematically analyzes scientific literature to identify microbial patterns, develop hypotheses, and validate interventions. As the founder of the Microbiome Signatures Database, she bridges microbiome research with clinical practice. In 2012, based on her own investigative research, she became the first documented case of FMT for Celiac Disease—four years before the first published case study.
Lugdunin is a microbiome-derived cyclic peptide antibiotic with direct anti-S. aureus activity and host immune-boosting effects. It induces L-37 and XCL8, recruits immune cells, and synergizes with host peptides, making it a promising candidate for RSA and atopic dermatitis interventions.
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Karen Pendergrass
Researched by:
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Karen Pendergrass
ID
Karen Pendergrass
Microbiome Signatures identifies and validates condition-specific microbiome shifts and interventions to accelerate clinical translation. Our multidisciplinary team supports clinicians, researchers, and innovators in turning microbiome science into actionable medicine.
Karen Pendergrass
Overview Overview
Lugdunin is a thiazolidine-containing cyclic peptide antibiotic biosynthesized by Staphylococcus lugdunensis, a nasal and skin commensal. It exhibits dual functionality: direct antimicrobial activity against Gram-positive bacteria, especially Staphylococcus aureus, and immunomodulatory effects through epithelial activation. Lugdunin disrupts bacterial membrane potential and integrity without engaging typical resistance pathways, resulting in rapid pathogen death. In parallel, lugdunin triggers Toll-like receptor (TLR)/MyD88 signaling in keratinocytes, leading to upregulation of CXCL8 (human) and MIP-2 (murine) and subsequent recruitment of phagocytic immune cells including monocytes and neutrophils.
Antimicrobial Activity
Lugdunin demonstrates potent bactericidal effects against methicillin-resistant S. aureus (MRSA), Bacillus subtilis, and vancomycin-resistant Enterococcus spp. through nonribosomal peptide synthesis. Its antimicrobial spectrum is broad within Gram-positive taxa, but it lacks significant effect on Gram-negative species. In vitro and murine models confirm its capacity to eradicate S. aureus from skin tissues and reduce epithelial colonization load, especially when co-administered with human antimicrobial peptides like LL-37 or dermcidin-derived peptides (DCD-1/L). The compound exhibits synergy with host AMPs, achieving higher efficacy in concurrent administration compared to sequential exposure.
Immunomodulatory Effects
Beyond direct antimicrobial action, lugdunin acts as a microbial immune adjuvant. It amplifies commensal-induced innate immune signaling in keratinocytes, upregulating LL-37, RNase7, and CXCL8 expression. Lugdunin-mediated epithelial conditioning occurs via a TLR2-dependent, MyD88-mediated pathway. This immune activation results in the recruitment of neutrophils and monocytes in vivo, establishing a multi-level defensive barrier. Additionally, lugdunin amplifies the effect of S. epidermidis-derived factors, enhancing skin barrier immunity synergistically.
Clinical Relevance and Potential Applications
Lugdunin represents a pioneering model of microbiome-derived antimicrobial therapy with simultaneous bactericidal and immunostimulatory properties. Its future therapeutic formulation could include topical applications or engineered live biotherapeutics based on S. lugdunensis.
| Application Context | Evidence Basis |
|---|---|
| Atopic Dermatitis | Disrupts S. aureus colonization; boosts LL-37 & CXCL8 |
| MRSA Skin Infections | Direct bactericidal activity and immune enhancement |
| Microbiome-Based Prophylaxis | Enhances colonization resistance via commensal synergy |
Research Fast-Track (RFT) Justification
Lugdunin qualifies as a Research Fast-Track (RFT) intervention due to its well-characterized mechanistic interactions across host-microbe and microbe-microbe interfaces. Preclinical studies demonstrate its robust efficacy in murine models of epithelial colonization, particularly in reducing Staphylococcus aureus burden. Its synergistic action with host immune pathways—such as TLR/MyD88 signaling and antimicrobial peptide induction—and its enhancement of commensal-derived immune modulation underscore its multifaceted functionality. Importantly, lugdunin shows no cytotoxicity in keratinocytes, epithelial cells, or peripheral blood mononuclear cells (PBMCs), supporting its safety profile. Given its capacity to suppress S. aureus, fortify skin barrier defenses, and potentiate innate immune responses, lugdunin holds high translational relevance for conditions like atopic dermatitis and MRSA-associated skin infections. Although not yet in clinical use, its reproducible immuno-antimicrobial effects substantiate its classification as an Experimental Microbiome-Targeted Intervention (MBTI) under the RFT designation.
Microbiome-Targeted Interventions (MBTIs)
Microbiome Targeted Interventions (MBTIs) are cutting-edge treatments that utilize information from Microbiome Signatures to modulate the microbiome, revolutionizing medicine with unparalleled precision and impact.