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János Tamás Padra , PhD University of Gothenburg, Sweden Mucins in Infection and Cancer Team

Aeromonas salmonicida proliferation and quorum sensing in response to mucins isolated from Atlantic salmon skin and intestine. János Tamás Padra , PhD University of Gothenburg, Sweden Mucins in Infection and Cancer Team. Furunculosis disease.

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János Tamás Padra , PhD University of Gothenburg, Sweden Mucins in Infection and Cancer Team

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  1. Aeromonas salmonicida proliferation and quorum sensing in response to mucins isolated from Atlantic salmon skin and intestine János Tamás Padra, PhD University of Gothenburg, Sweden Mucins in Infection and Cancer Team

  2. Furunculosis disease • Causative agent of furunculosis disease: Aeromonas salmonicida • Gram-negative, facultative anaerobic, non-motile rod • Furuncle-like swelling, ulcerative lesions, bowel inflammation – often fatal • Infectsmainly salmonids butdescribed in otherfish species in contactwith salmonids • A. salmonicida has a devastating impact on cultivated fish, particularly the Salmonids

  3. Role of Mucins • Form mucus layer with other secretions • Barrier function • Dense carbohydrate coating can hold water • Protects against proteolysis • Lubrication • Other

  4. Sites of interest • Skin

  5. Mucin structure • 2-11 residues in glycan chains • Skin O-glycans are short (2-5) • Intestinal mucin O-glycans are longer (up till 11)

  6. Previous results

  7. The salmon O-glycans are highly sialylated (78-90%) • Jin et al., 2015

  8. AB-PAS staining • Skin • Pyloric ceca • Distal intestine • Proximal intestine • Jin et al., 2015

  9. Intestinal mucins promote A. salmonicida growth • Defined medium (DM)+Glucose • DM only • 30 min • 160 min

  10. Adhesion – dual role? • DM+Glucose • DM

  11. ”Large” mucins nurture better • DM+Glucose • DM

  12. Do sialic acids promote growth? • DM+Glucose • DM

  13. Aeromonas salmonicida – tactics of colonization • A. salmonicida is provided with tools to degrade mucins and use as C-source • β-galactosidase • β-N-acetylhexosaminidase • GlcNAc-6-phosphate deacetylase • Glucosamine-6-phosphate deaminase • Sialidase?

  14. Sialidase present?

  15. Mucin building blocks on proliferation

  16. Desialylated mucins further increase growth

  17. Quorum sensing • A form of communication with small molecules • Responsible for the group behaviour of bacteria • Alters metabolism, luminescence, virulence etc. • Three forms are known at present: • Intra-species communication • Inter-species communication • Vibrio intra genera communication

  18. Aeromonas salmonicida ”language” • Autoinducer-1 – Acylhomoserine lactons • AsaI-autoinducer synthase • AsaR-autoinducer receptor • Autoinducer-2 system – A. hydrophila – 4,5-Dihydroxy-2,3-pentanedione • LuxS-autoinducer synthase • LuxP-autoinducer receptor • LuxU-autoinducer phosphorelay protein • LuxO-autoinducer regulator • Other system(s)???

  19. Effect of autoinduction on growth • N-Butyryl-homoserine lactone • (BOC Sciences) • (S)-4,5-Dihydroxy-2,3-pentandione (DPD, AI-2)Autoinducer-2

  20. BHL (C4 HSL) growth response

  21. DPD growth response

  22. Ai-2 timecourse

  23. Mucins Ai-2 communication

  24. Reduction in sialic acids differentially affects QS in the organ groups

  25. Conclusion • Intestinal mucins feed the bacteriabutreduce the levelofcommunication. Balancingbetweencommensals and pathogensthrough AI-1 system? • Skin mucins seemto be inhibitory for A. salmonicida colonization and infection. • Sialic acids in Proximal intestine and Skin has an especiallyhighimportance in QS • AI-1 and AI-2 timecoursewith mucin effect

  26. Acknowledgements • Prof. Sara Lindén , Dr. Chunsheng Jin and the rest of the Mucins in Infection and Cancer Team • Prof. Kristina Sundell • Dr. Henrik Sundh

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