Restoring Quorum-Sensing Function of Staphylococcus epidermidis to Reverse Alcohol-Induced Hand Skin Microbiome Dysbiosis
Abstract
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
Full Text:
PDFReferences
[1] Creech, C. B., Al-Zubeidi, D. N., & Fritz, S. A. (2015). Prevention of recurrent staphylococcal skin infections. Clinical Infectious Diseases, 61(4), 576582.
[2] Frohm, M., Agerberth, B., Ahangari, G., Sthle-Bckdahl, M., Lidn, S., Wigzell, H., & Gudmundsson, G. H. (1997). The expression
of the gene coding for the antibacterial peptide LL-37 is induced in human keratinocytes. Journal of Investigative Dermatology, 108(3),
381386.
[3] Inagaki, R., et al. (2024). Eliminating extracellular autoinducing peptide signals to inhibit agr quorum sensing in Staphylococcus aureus.
Biochemical and Biophysical Research Communications.
[4] Kramer, A., et al. (2025). No detrimental effect on the hand microbiome of health professionals after ABHR. American Journal of Infection Control.
[5] Le, K. Y., Otto, M., & others. (2015). Quorum-sensing regulation in staphylococcian overview. Frontiers in Microbiology, 6, 1174.
[6] Levy, E. S., et al. (2021). A systematic approach for liposome and lipodisk formulation screening. Pharmaceutics, 13(10), 1627.
[7] Lupu, A., et al. (2023). Self-healing of Pluronic F127 hydrogels in the presence of polysaccharides. Gels, 9(9), 686.
[8] Mukherjee, P. K., et al. (2017). Effect of ABHR on hand bacteriome and mycobiome. Mycopathologia, 182, 112.
[9] Mukherjee, P. K., et al. (2018). Effect of ABHR on hand microbiome and skin health in transplant patients. Journal of the American
Academy of Dermatology, 78(3), 655661.
[10] Nie, S., et al. (2011). Thermoreversible Pluronic F127-based hydrogel for drug delivery. International Journal of Nanomedicine, 6,
8594.
[11] Olson, M. E., et al. (2014). Staphylococcus epidermidis agr quorum-sensing system. Infection and Immunity, 82(3), 10451055.
[12] Ridyard, K. E., & Overhage, J. (2021). The potential of LL-37 as an antimicrobial and immunomodulatory agent. Antibiotics, 10(6),
698.
[13] Schubert, M., et al. (2019). MRSA carriage among employees. Journal of Occupational Medicine and Toxicology, 14, 7.
[14] Shriky, B., et al. (2020). Pluronic F127 thermosensitive hydrogels for injectable delivery. Journal of Colloid and Interface Science, 565,
119130.
[15] van der Does, A. M., et al. (2012). Induction of LL-37 by vitamin D3. Journal of Leukocyte Biology, 92(5), 829839.
[16] Vindenes, H. K., et al. (2023). Impact of ABHS and soap on skin microbiome. Journal of Cosmetic Dermatology, 22(10), e214.
[17] Voronko, O. E., et al. (2025). Cathelicidins with focus on LL-37: modifications and applications. International Journal of Molecular Sciences, 26(16), 8103.
[18] Williams, P., et al. (2023). Quorum-sensing, intra- and inter-species competition in staphylococci. Microbiology, 169(6), 001381.
DOI: http://dx.doi.org/10.70711/pmr.v3i2.8392
Refbacks
- There are currently no refbacks.