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.

Topical Antimicrobial Treatments Can Elicit Shifts to Resident Skin Bacterial Communities and Reduce Colonization by Staphylococcus aureus Competitors

“…As previous studies have illustrated the role of certain Staphylococcus spp. to compete with S. aureus for colonization (27)(28)(29), we proceeded by testing the ability of murine Staphylococcus isolates to compete with S. aureus. Specifically, we chose Staphylococcus residents that were disrupted by antibiotic and antiseptic treatment in our previous experiments for further analysis.…”

“…This includes defense against Staphylococcus aureus by unique strains of S. epidermidis (27), S. lugdunensis (28), and most recently, S. hominis (29). Here, it was found that certain individuals are colonized by host-specific Staphylococcus strains with the ability to alter S. aureus colonization patterns.…”

Co-Habitation of <i>Staphylococcus lugdunensis</i> with <i>Staphylococcus aureus</i> Resistant to Methicillin and Vancomycin in the Nasal Snares of Laboratory Rats

“…This bacterium that can also be found colonising the nasal snares is said to have the capability to kill S. aureus, as has been reported by various researchers [6] [7] [8]. S. lugdunensis is said to produce lugdunin a novel thiazolidine-containing cycle peptide antibiotic that acts in inhibiting colonisation of S. aureus [6]. These researchers suggested that lugdunin producing S. lugdunensis could be valuable in preventing Staphylococcal infections as well as being effective against strains of MRSA.…”

“…Recently, however, attention is drawn to a proposed new antibiotic "Lugdunin" reported to be a product from Staphylococcus lugdunensis. This bacterium that can also be found colonising the nasal snares is said to have the capability to kill S. aureus, as has been reported by various researchers [6] [7] [8]. S. lugdunensis is said to produce lugdunin a novel thiazolidine-containing cycle peptide antibiotic that acts in inhibiting colonisation of S. aureus [6].…”

“…These researchers suggested that lugdunin producing S. lugdunensis could be valuable in preventing Staphylococcal infections as well as being effective against strains of MRSA. Zipper et al [6], indicated that it was not yet clear how lugdunin worked, but postulated the bacterium to be a powerful enemy of S. aureus.…”