Human commensals producing a novel antibiotic impair pathogen colonization

Area of Science:

• Microbiology and Infectious Diseases
• Drug Discovery and Development
• Human Microbiome Research

Background:

• Systemic bacterial infections often stem from antibiotic-resistant pathogens colonizing human surfaces.
• Nasal carriage of Staphylococcus aureus is a known risk factor for invasive infections, but colonization mechanisms are poorly understood.
• Antibiotic production by human commensal bacteria, unlike soil microbes, is rarely reported.

Purpose of the Study:

• To investigate the mechanisms of pathogen colonization on human body surfaces, specifically nasal carriage.
• To identify novel antimicrobial compounds produced by human commensal bacteria.
• To explore the potential of these compounds and bacteria for preventing staphylococcal infections.

Main Methods:

• Identification and characterization of antimicrobial compounds produced by nasal Staphylococcus lugdunensis strains.
• Determination of the chemical structure and properties of the novel antibiotic, lugdunin.
• Assessment of lugdunin's bactericidal activity against major pathogens and its efficacy in animal models.
• Evaluation of S. lugdunensis colonization rates in humans and its association with S. aureus carriage.

Main Results:

• Staphylococcus lugdunensis produces lugdunin, a novel cyclic peptide antibiotic.
• Lugdunin exhibits bactericidal activity against major pathogens and is effective in animal models without readily inducing resistance in S. aureus.
• Human nasal colonization by S. lugdunensis correlates with significantly reduced S. aureus carriage rates.

Conclusions:

• Lugdunin is a potent antibiotic produced by a human commensal bacterium, effective against key pathogens.
• Lugdunin-producing commensal bacteria, like S. lugdunensis, show promise for preventing staphylococcal infections.
• The human microbiota represents a valuable, yet underexplored, source for novel antibiotic discovery.