Commensal Friends or Foes? Bacterial Injection Systems in Skin Microbiomes and Commensals As Novel Avenue for Combatting Infections and Antimicrobial Resistance

The skin microbiome plays a crucial role in maintaining skin homeostasis, protection against pathogens, and modulating immune response.

It also is a hot spot for antimicrobial resistance e.g., about 40% of the Staphylococcus aureus (MRSA) strains in wounds showing resistance to methicillin.

The targeted delivery of antimicrobials into pathogens, leaving commensal microbiota unharmed, would enhance wound healing, combat infections and resistance. Nature offers a promising solution: contractile injection systems (CIS).

These nano syringes, predominantly found in environmental microbes, are complex injection machines, refined through evolution to gain competitive advantages. They are capable of transporting drugs across biological membranes. Recent studies have identified CIS in gut bacteria like Bacteroides, predominant in healthy human guts.

Our research aims to explore CIS in skin microbiomes, elucidating their structures, functions, and interactions with commensal communities. Using state-of-the-art sequencing and imaging techniques, we will profile healthy skin microbiota and CIS thereof.

We will investigate CIS targeting, assess their efficacy against MRSA, and explore their importance through CRISPR gene editing. Additionally, we will develop CIS-based therapies using protein design, tailored to combat bacterial skin infections.

This proposal seeks to advance understanding of skin microbiota, CIS, and their potential for topical drug delivery against notorios MRSA.