Collateral damage of antibiotic eradication targeting nasal Staphylococcus aureus requires alternative decolonization strategies

Question: Staphylococcus aureus is a major human pathogen which causes a wide variety of infections. S. aureus colonizes approximately the nares of 20% of the human population. Decolonization treatments prior to invasive medical inventions lead to a reduced risk in subsequent infections. The proven method for decolonization of S. aureus is a treatment with the antibiotic mupirocin, which leads to problems on the long run. Firstly S. aureus recolonizes usually after the treatment has stopped. Secondly antibiotic resistance to mupirocin in S. aureus is emerging. In addition, S. aureus is part of a complex microbiome in the human nares. Other bacterial species have promoting or suppressive effects on S. aureus nasal colonization. The effect of mupirocin treatment on the nasal microbiome is poorly understood on the species and strain level. In this study we determine the global effect of nasal decolonization strategies on the nasal microbiome. Furthermore, we propose potential alternative methods with increased precision and selectivity.

Methods: We used a combination of in vitro techniques and in silico prediction to determine antibiotic susceptibility and colonization dynamics upon mupirocin treatment of a comprehensive collection of nasal commensals. Furthermore, we validated our results with in vivo colonization data.

Results: We show that presence of certain alleles of the mupirocin target explains antibiotic resistance across a wide variety of nasal commensals from very diverse phylogenetic clades. Presence of identified resistance determinants governs growth in a competitive in vitro system. Observed microbiome disturbances caused by mupirocin treatment correlate well with in vivo colonization data.

Conclusion: We show that mupirocin treatment has notable collateral side effects on nasal commensals perturbing the composition of nasal microbiomes. Side effects are especially pronounced on other- often harmless - commensal staphylococci, which are frequently antagonizing S. aureus colonization. Hence, we propose alternative antimicrobial approaches targeting molecular structures which are unique to pathogenic commensals. A promising alternative could be bacteriophages, microbial viruses. In contrast to frequently used antibiotics bacteriophages target distinct surface structures that are unique to S. aureus allowing potentially selective and controlled eradication of this pathogens from the human nose.