Small proline-rich proteins (SPRRs) are epidermally produced antimicrobial proteins that defend the cutaneous barrier by direct bacterial membrane disruption
- ShanghaiTech University, China
- The University of Texas Southwestern Medical Center, United States
- Brandenburg Medical School Theodore Fontane, Germany
Abstract
Human skin functions as a physical barrier, preventing the entry of foreign pathogens while also accommodating a myriad of commensal microorganisms. A key contributor to the skin landscape is the sebaceous gland. Mice devoid of sebocytes are prone to skin infection, yet our understanding of how sebocytes function in host defense is incomplete. Here we show that the small proline-rich proteins, SPRR1 and SPRR2 are bactericidal in skin. SPRR1B and SPPR2A were induced in human sebocytes by exposure to the bacterial cell wall component lipopolysaccharide (LPS). Colonization of germ-free mice was insufficient to trigger increased SPRR expression in mouse skin, but LPS injected into mouse skin triggered the expression of the mouse SPRR orthologous genes, Sprr1a and Sprr2a, through stimulation of MYD88. Both mouse and human SPRR proteins displayed potent bactericidal activity against MRSA (methicillin-resistant Staphylococcus aureus), Pseudomonas aeruginosa and skin commensals. Thus, Sprr1a-/-;Sprr2a-/- mice are more susceptible to MRSA and Pseudomonas aeruginosa skin infection. Lastly, mechanistic studies demonstrate that SPRR proteins exert their bactericidal activity through binding and disruption of the bacterial membrane. Taken together, these findings provide insight into the regulation and antimicrobial function of SPRR proteins in skin and how the skin defends the host against systemic infection.
Data availability
RNA-seq data (Figures 1B,1C) has been submitted to the Gene Expression Omnibus with an accession number: GSE182756
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Small proline-rich proteins 1 and 2 function as antimicrobial proteins in the skinNCBI Gene Expression Omnibus, GSE182756.
Article and author information
Author details
Christos C Zouboulis
Tamia A Harris-Tryon
Funding
National Institutes of Health (AR076459-01)
- Tamia A Harris-Tryon
Robert Wood Johnson Foundation (Amos)
- Tamia A Harris-Tryon
Burroughs Wellcome Fund (CAMS)
- Tamia A Harris-Tryon
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Ethics
Animal experimentation: This study was performed in strict accordance with the recommendations in the Guide for the Care and Use of Laboratory Animals of the National Institutes of Health. All of the animals were handled according to approved institutional animal care and use committee (IACUC) protocols of the University of Texas Southwestern, protocol number 2015-101064. All surgery was performed under isoflurane anesthesia, and every effort was made to minimize suffering.
Copyright
© 2022, Zhang et al.
This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.
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