Engineering a "detect and destroy" skin probiotic to combat methicillin-resistant Staphylococcus aureus.

Changhui Guan, The Jackson Laboratory
Peter J Larson, The Jackson Laboratory
Elizabeth Fleming, The Jackson Laboratory
Alexander P Tikhonov
Sara Mootien
Trudy H Grossman
Caroline Golino
Julia Oh, The Jackson Laboratory

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The prevalence and virulence of pathogens such as methicillin-resistant Staphylococcus (S.) aureus (MRSA), which can cause recurrent skin infections, are of significant clinical concern. Prolonged antibiotic exposure to treat or decolonize S. aureus contributes to development of antibiotic resistance, as well as depletion of the microbiome, and its numerous beneficial functions. We hypothesized an engineered skin probiotic with the ability to selectively deliver antimicrobials only in the presence of the target organism could provide local bioremediation of pathogen colonization. We constructed a biosensing S. epidermidis capable of detecting the presence of S. aureus quorum sensing autoinducer peptide and producing lysostaphin in response. Here, we demonstrate in vitro activity of this biosensor and present and discuss challenges to deployment of this and other engineered topical skin probiotics.