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Peer-reviewedCC BY-NC-NDNature communications

The urinary pathobiont Actinobaculum massiliense can generate androgens via the dirAB pathway.

  • Taojun Wang1,2
  • Saeed Ahmad3
  • Raissa Santos de Lima Rosa4,5
  • Briawna Binion1,2
  • Francelys V Fernandez-Materan1,2
  • Jimoh Olamilekan Igbalaye3
  • David Chung3
  • Anika Bushra3
  • Vince Perez3
  • Michael A Biedak2
  • Elizabeth Tang6
  • Betsy Barnick7
9 more authors
  • Damie Olukoya7
  • Pauline Mbuvi7
  • Debapriya Dutta7
  • John W Erdman8,9
  • H Rex Gaskins1,2,8,9
  • Glen Yang10
  • Joseph Irudayaraj1,3,8,9,11,12
  • Rafael C Bernardi4,5
  • Jason M Ridlon13,14,15,16,17,18
18 affiliations
  1. 1Carl R. Woese Institute for Genomic Biology, Urbana, IL, USA.
  2. 2Department of Animal Sciences, University of Illinois at Urbana-Champaign, Urbana, IL, USA.
  3. 3Department of Bioengineering, University of Illinois at Urbana-Champaign, Urbana, IL, USA.
  4. 4Department of Physics, Auburn University, Auburn, AL, USA.
  5. 5Department of Chemistry and Biochemistry, Auburn University, Auburn, AL, USA.
  6. 6Department of Physics, University of Illinois Urbana-Champaign, Urbana, IL, USA.
  7. 7Carle Cancer Center, Urbana, IL, USA.
  8. 8Division of Nutritional Sciences, University of Illinois at Urbana-Champaign, Urbana, IL, USA.
  9. 9Cancer Center at Illinois, University of Illinois at Urbana-Champaign, Urbana, IL, USA.
  10. 10Department of Urology, Carle Foundation Hospital, Urbana, IL, USA.
  11. 11Biomedical Research Center, Mills Breast Cancer Institute, Carle Foundation Hospital, Urbana, IL, USA.
  12. 12Carle-Illinois College of Medicine, University of Illinois Urbana- Champaign, Urbana, IL, USA.
  13. 13Carl R. Woese Institute for Genomic Biology, Urbana, IL, USA. [email protected].
  14. 14Department of Animal Sciences, University of Illinois at Urbana-Champaign, Urbana, IL, USA. [email protected].
  15. 15Division of Nutritional Sciences, University of Illinois at Urbana-Champaign, Urbana, IL, USA. [email protected].
  16. 16Cancer Center at Illinois, University of Illinois at Urbana-Champaign, Urbana, IL, USA. [email protected].
  17. 17Center for Advanced Study, University of Illinois Urbana-Champaign, Urbana, IL, USA. [email protected].
  18. 18Department of Microbiology and Immunology, Virginia Commonwealth University School of Medicine, Richmond, VA, USA. [email protected].
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Abstract

While overlooked during the Human Microbiome Project, characterizing the urinary microbiota in health and disease is a new frontier in microbiome science. Recent studies have associated differential abundance of bacterial taxa including Propionimicrobium lymphophilum and Actinobaculum/Actinotignum spp. with prostate cancer. In this study, we collected urine from subjects before prostate biopsy and applied a Human Sterolbiome Discovery High-throughput (HSDH) assay to identify culturable urinary bacteria with the ability to generate androgens. Application of the HSDH Assay to urine samples led to the isolation of eight P. lymphophilum strains positive for cortisol side-chain cleavage (steroid-17,20-desmolase), 17β-HSDH activity, or both. In addition, we isolated three strains of Actinobaculum massiliense that carry the DHEA isomerase reductase (dir) genes. The dirA gene encodes a multifunctional 3β/17β-hydroxysteroid dehydrogenase/Δ4,5-isomerase and the dirB gene encodes a 17β-hydroxysteroid dehydrogenase isoform. Structural prediction and molecular dynamics reveal probable catalytic mechanisms based on the shared catalytic triad but distinct binding-pocket geometries of DirA and DirB, which enabled predictions of their respective reactions. Phylogenetic analysis of DirA and DirB revealed homologs in urinary tract commensals and in bacteria associated with steroid degradation in aquatic and terrestrial environments. Taken together, the development of the HSDH Assay and the identification of the dir pathway genes provide the methodological foundation and provide the molecular basis for advancing our understanding of the role of urinary tract bacteria in host endocrine physiology.

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Cite

BibTeXRIS
BibTeX
@article{wang2026urinary,
  title = {{The urinary pathobiont Actinobaculum massiliense can generate androgens via the dirAB pathway.}},
  author = {Taojun Wang and Saeed Ahmad and Raissa Santos de Lima Rosa and Briawna Binion and Francelys V Fernandez-Materan and Jimoh Olamilekan Igbalaye and David Chung and Anika Bushra and Vince Perez and Michael A Biedak and Elizabeth Tang and Betsy Barnick and Damie Olukoya and Pauline Mbuvi and Debapriya Dutta and John W Erdman and H Rex Gaskins and Glen Yang and Joseph Irudayaraj and Rafael C Bernardi and Jason M Ridlon},
  journal = {Nature communications},
  year = {2026},
  month = sep,
  doi = {10.1038/s41467-026-77382-7},
  url = {https://europepmc.org/article/MED/42834054},
  note = {CC BY-NC-ND},
}
RIS
TY  - JOUR
TI  - The urinary pathobiont Actinobaculum massiliense can generate androgens via the dirAB pathway.
AU  - Taojun Wang
AU  - Saeed Ahmad
AU  - Raissa Santos de Lima Rosa
AU  - Briawna Binion
AU  - Francelys V Fernandez-Materan
AU  - Jimoh Olamilekan Igbalaye
AU  - David Chung
AU  - Anika Bushra
AU  - Vince Perez
AU  - Michael A Biedak
AU  - Elizabeth Tang
AU  - Betsy Barnick
AU  - Damie Olukoya
AU  - Pauline Mbuvi
AU  - Debapriya Dutta
AU  - John W Erdman
AU  - H Rex Gaskins
AU  - Glen Yang
AU  - Joseph Irudayaraj
AU  - Rafael C Bernardi
AU  - Jason M Ridlon
PY  - 2026
DA  - 2026/09/03
JO  - Nature communications
DO  - 10.1038/s41467-026-77382-7
UR  - https://europepmc.org/article/MED/42834054
AB  - While overlooked during the Human Microbiome Project, characterizing the urinary microbiota in health and disease is a new frontier in microbiome science. Recent studies have associated differential abundance of bacterial taxa including Propionimicrobium lymphophilum and Actinobaculum/Actinotignum spp. with prostate cancer. In this study, we collected urine from subjects before prostate biopsy and applied a Human Sterolbiome Discovery High-throughput (HSDH) assay to identify culturable urinary bacteria with the ability to generate androgens. Application of the HSDH Assay to urine samples led to the isolation of eight P. lymphophilum strains positive for cortisol side-chain cleavage (steroid-17,20-desmolase), 17β-HSDH activity, or both. In addition, we isolated three strains of Actinobaculum massiliense that carry the DHEA isomerase reductase (dir) genes. The dirA gene encodes a multifunctional 3β/17β-hydroxysteroid dehydrogenase/Δ4,5-isomerase and the dirB gene encodes a 17β-hydroxysteroid dehydrogenase isoform. Structural prediction and molecular dynamics reveal probable catalytic mechanisms based on the shared catalytic triad but distinct binding-pocket geometries of DirA and DirB, which enabled predictions of their respective reactions. Phylogenetic analysis of DirA and DirB revealed homologs in urinary tract commensals and in bacteria associated with steroid degradation in aquatic and terrestrial environments. Taken together, the development of the HSDH Assay and the identification of the dir pathway genes provide the methodological foundation and provide the molecular basis for advancing our understanding of the role of urinary tract bacteria in host endocrine physiology.
SN  - 2041-1723
ER  -