Muhammed, H. | bioRxiv Science

bioRxiv2026

Emended description of the genus Henriciella: morphological and phylogenetic analysis identifies two subgenera with different reproductive strategies

Henriciella is the only genus with reported non-prosthecate members in the family Hyphomonadaceae, a large group of dimorphic prosthecate bacteria. Using type strains, we reinvestigated growth in media shown to support prosthecate morphotypes in marine caulobacters. We report that Marine Broth (MB) and Peptone Yeast Extract (PYE)-derived media supported prosthecate populations for all Henriciella species. Surprisingly, we observed that H. aquimarina, H. mobilis, and H. pelagia reproduce by tip budding whereas H. marina and H. liltoralis reproduce by asymmetric binary fission. These two observed reproductive strategies resemble those characterized for the model prosthecate bacteria Hyphomonas neptunium and Caulobacter crescentus. Phylogenomic analysis indicates that H. marina, H. litoralis, H. algicola, and H. barbarensis form a monophyletic subgenus that reproduces by asymmetric binary fission. We propose genus and species emendations that correct the record on this fascinating genus.

microbiology↗

bioRxiv2021

Variants in ALDH1A2 reveal an anti-inflammatory role for retinoic acid and a new class of disease-modifying drugs in osteoarthritis

Over 40% of individuals will develop osteoarthritis (OA) during their lifetime, yet there are currently no licensed disease modifying treatments for this disabling condition. Common polymorphic variants in ALDH1A2, that encodes the key enzyme in the synthesis of all-trans retinoic acid (atRA), have been associated with severe hand OA. In this study, we sought to elucidate the biological significance of this association. We first confirmed that ALDH1A2 risk variants were associated with hand OA in UK Biobank. Articular cartilage was acquired from 33 consenting individuals with hand OA at the time of routine hand OA surgery. They were stratified by genotype and RNA sequencing performed. A reciprocal relationship between ALDH1A2 mRNA and inflammatory genes was observed. Articular cartilage injury up-regulates similar inflammatory genes by a process that we have previously termed mechanoflammation, and which we believe is a primary driver of OA. Cartilage injury was also associated with a concomitant drop in atRA-dependent genes, indicative of cellular atRA levels, and both responses to injury were reversed using talarozole, a retinoic acid metabolism blocking agent (RAMBA). Suppression of mechanoflammation by talarozole was mediated by a peroxisome proliferator activated receptor (PPAR)-{gamma} dependent mechanism. Talarozole, delivered by minipump, was able to suppress mechano-inflammatory genes in articular cartilage in vivo 6h after mouse knee joint destabilization, and reduced cartilage degradation and osteophyte formation after 4 weeks. These data show that boosting atRA suppresses mechanoflammation in the articular cartilage in vitro and in vivo, and identifies RAMBAs as potential disease modifying drugs in OA. One Sentence SummaryAnalysis of hand OA cartilage stratified by ALDH1A2 polymorphic variants reveals a targetable, anti-inflammatory role for retinoic acid in OA.

molecular biology↗