Unraveling the role of actinotignum schaalii in hidradenitis suppurativa: Genomic and inflammatory perspectives

Summary: Abstract Body: Hidradenitis suppurativa (HS) is a debilitating chronic skin disease characterized by recurrent painful lesions, scarring, and malodorous discharge. While microbial dysbiosis is recognized in HS sinus tracts, the contributions of individual microbes to disease progression remain insufficiently explored. This study focuses on Actinotignum schaalii, a Gram-positive facultative anaerobe, and its potential role in HS pathogenesis. Using traditional culture methods, A. schaalii was isolated from severe HS lesions. Whole genome sequencing revealed a suite of virulence-associated genes, including those linked to adhesion, intracellular invasion, antimicrobial resistance, and oxidative stress tolerance. Functional assays demonstrated that ex-vivo infection of human skin with A. schaalii significantly upregulated pro-inflammatory cytokines seen in HS. In vivo experiments in murine models confirmed that A. schaalii induces acute abscess formation, mirroring the inflammatory features observed in HS. These findings suggest that A. schaalii actively contributes to the inflammatory milieu of HS and may represent a novel therapeutic target. This research also establishes a scalable methodology for studying additional anaerobic bacteria implicated in HS, advancing our understanding of bacterial-driven mechanisms in disease progression. Tammy Gonzalez¹, Sujad Younis¹, Melissa Hernandez², Fernando Salinas³, Elina Zhivov¹, Laura I. Padula¹, Natasa Strbo¹, Hadar Lev-Tov¹, Barry Resnik¹, Irena Pastar¹ 1. Dermatology, University of Miami Miller School of Medicine, Miami, FL, United States. 2. Loyola University Chicago, Chicago, IL, United States. 3. Ponce Health Sciences University, Ponce, Ponce, Puerto Rico. Innate Immunity, Microbiology, and Microbiome