Sugar glider cathelicidins—antimicrobial peptides expanded in marsupial genomes—are highly expressed in neonatal neutrophils, modulate immune responses, and provide sufficient antibacterial protection against sepsis in a mouse model.
Sepsis protectionMarsupial cathelicidin peptides provided sufficient antibacterial activity to protect mice from sepsis, despite evolving for marsupial neonatal defense
What the researchers found
Sugar glider cathelicidins reside in two genomic clusters, are highly expressed in neonatal neutrophils, have potent antibacterial activity, modulate immune responses, and provide sufficient protection against sepsis in a mouse model. Marsupials and monotremes uniquely retain both genomic clusters among tetrapods.
Why it matters
Cathelicidins are a crucial family of antimicrobial peptides shared across mammals, including humans (LL-37). Discovering that marsupials have an expanded repertoire with proven sepsis protection could inspire novel peptide-based anti-infective therapies and reveal new biology about how these peptides evolved to meet different immune challenges.
The numbers in context
Sugar glider cathelicidins reside in two genomic clusters with shared enhancers and long-range interactions. Provided protection in a mouse sepsis model. Marsupials and monotremes uniquely retain both clusters among tetrapods.
How the study worked
Genomic analysis of cathelicidin gene clusters, gene expression profiling in developing neutrophils, functional antibacterial and immunomodulatory assays, and in vivo sepsis protection testing in a mouse model using sugar glider (Petaurus breviceps).
Who was studied
Sugar glider (Petaurus breviceps) neonates and mouse sepsis model
What this study cannot tell us
Primary focus on marsupial biology limits direct human clinical translation. Mouse sepsis model provides proof of concept but is not equivalent to human infection. Specific peptide sequences with greatest therapeutic potential were not individually characterized. Evolutionary focus may limit practical application.
How to read the evidence
Rigorous genomic, functional, and in vivo study combining evolutionary biology with therapeutic proof-of-concept. Strong mechanistic evidence but limited by the marsupial-to-human translational gap.
When this study was published
Published in 2025; represents cutting-edge research at the intersection of evolutionary immunology and antimicrobial peptide biology.
The bigger picture
This study reveals that evolution has produced diverse solutions to immune defense through antimicrobial peptide expansion. The marsupial cathelicidin repertoire—selected over millions of years for neonates born without a mature immune system—may contain peptides with therapeutic properties not found in the single human cathelicidin (LL-37).
Questions still open
- Could specific marsupial cathelicidin sequences be developed as novel anti-infective drugs for human sepsis?
- Why did placental mammals lose one cathelicidin cluster while marsupials retained both?
- Do the immunomodulatory properties of sugar glider cathelicidins differ from human LL-37 in therapeutically relevant ways?
Common questions
What are cathelicidins and why do marsupials have so many?
Could marsupial peptides be used as human medicines?
Read the original research
Cathelicidin antimicrobial peptides mediate immune protection in marsupial neonates.
Science advances, 11(16), eads6359
Citation
Park, Jongbeom; Ke, Wenfan; Kaage, Aellah; Feigin, Charles Y; Griffing, Aaron H; Pritykin, Yuri; Donia, Mohamed S; Mallarino, Ricardo. (2025). Cathelicidin antimicrobial peptides mediate immune protection in marsupial neonates.. Science advances, 11(16), eads6359. https://doi.org/10.1126/sciadv.ads6359