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Updated: Oct 1, 2025
Production and Visualization of Bacterial Spheroplasts and Protoplasts to Characterize Antimicrobial Peptide Localization
Published on: August 11, 2018
Small proline-rich proteins (SPRRs) are epidermally produced antimicrobial proteins that defend the cutaneous barrier
Chenlu Zhang1,2, Zehan Hu3,4, Abdul G Lone1
1Department of Dermatology, University of Texas Southwestern Medical Center, Dallas, United States.
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 stimulated increased expression of the mouse SPRR orthologous genes, Sprr1a and Sprr2a, through activation 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 mice are more susceptible to MRSA and P. 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.
Insights
Small proline-rich proteins (SPRR1 and SPRR2) kill bacteria on skin. These proteins, produced by sebocytes, protect against infections like MRSA and Pseudomonas aeruginosa by disrupting bacterial membranes.
Area of Science:
- Microbiology
- Dermatology
- Immunology
Background:
- The skin's physical barrier prevents pathogen entry but hosts commensal microbes.
- Sebaceous glands and their cells (sebocytes) are crucial to skin health.
- The role of sebocytes in host defense against infection is not fully understood.
Purpose of the Study:
- To investigate the antimicrobial function of small proline-rich proteins (SPRR1 and SPRR2) in human and mouse skin.
- To understand the regulation of SPRR proteins in response to bacterial components.
- To determine the mechanism by which SPRR proteins exert their bactericidal activity.
Main Methods:
- Induction of SPRR1B and SPRR2A in human sebocytes by lipopolysaccharide (LPS).
- Stimulation of mouse SPRR orthologs (Sprr1a and Sprr2a) expression via LPS injection and MYD88 activation.
- Testing bactericidal activity of SPRR proteins against MRSA, P. aeruginosa, and skin commensals.
- Investigating SPRR protein mechanism of action on bacterial membranes.
Main Results:
- SPRR1B and SPRR2A expression increased in human sebocytes upon LPS exposure.
- LPS injection in mouse skin induced Sprr1a and Sprr2a expression via MYD88.
- Both human and mouse SPRR proteins showed potent bactericidal effects against tested bacteria.
- Sprr1a-deficient mice exhibited increased susceptibility to MRSA and P. aeruginosa skin infections.
- SPRR proteins disrupt bacterial membranes to kill bacteria.
Conclusions:
- SPRR1 and SPRR2 proteins possess significant bactericidal activity in the skin.
- Sebaceous gland-derived SPRR proteins are key components of the skin's innate immune defense.
- Understanding SPRR function offers insights into preventing and treating skin infections.
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