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Restoring Quorum-Sensing Function of Staphylococcus epidermidis to Reverse Alcohol-Induced Hand Skin Microbiome Dysbiosis

Jiaxiang Tang

Abstract


Alcohol-based hand rubs (ABHRs) are indispensable in healthcare but may perturb the hand skin microbiome. We hypothesized that
ABHR transiently depletes Staphylococcus epidermidis (Se) autoinducing peptide (AIP) signaling, suppressing keratinocyte cathelicidin (LL-
37) and predisposing to methicillin-resistant Staphylococcus aureus (MRSA) colonization. Methods: We modeled ABHR exposure in vitro,
quantified AIP decay by LC-MS/MS, performed virtual/experimental screening for ethanol-stable cyclic peptide AIP analogs, and formulated
an AIP-analogloaded DSPC/cholesterol/DSPE-PEG2000 liposomal thermogel (Pluronic F127) patch for topical rescue. We evaluated LL-37
secretion and CAMP expression in HaCaT co-cultures and conducted a randomized pilot in healthcare workers comparing patch vs. petrolatum after routine hand disinfection. Results: Ethanol (35%) induced rapid, one-phase AIP decay (k?0.55 min-
), whereas selected analogs
retained ?85% intensity after 24 h. Liposomes (mean 185 nm) achieved ~88% encapsulation and released payload to ~8090% over 60 min at
33 C. In co-culture, LL-37 fell under ethanol but was restored to near-baseline with patch eluate. Clinically, the patch arm showed increased Se
abundance and decreased MRSA load over 4 weeks versus control. Conclusions: Restoring Se quorum-sensing with an ethanol-stable AIP analog
delivered by a thermogel patch may reverse ABHR-associated dysbiosis and reduce MRSA colonization risk. Larger trials are warranted.

Keywords


Staphylococcus epidermidis; Quorum sensing; AIP; LL-37; MRSA; Alcohol-based hand rub; Liposomes; Pluronic F127; Thermogel; Skin microbiome

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References


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DOI: http://dx.doi.org/10.70711/pmr.v3i2.8392

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