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Wound-Healing Bacteria Greg Goals • Bacteria that could be spread on a wound – Would prevent infections from other bacteria – Would encourage growth of scabs/skin – Would be resistant to or hidden from immune system Challenges • Immune resistance cannot spread to other bacteria – Make immune resistance a multistep process requiring more than one protein • Bacteria cannot spread beyond wound – Could upset balance of other beneficial bacteria in gut or kill them off – Link bacterial growth/production of antibacterial stuff to conditions of wounded skin Stopping other infections • Identify method by which harmful bacteria infect a wound – http://www.ncbi.nlm.nih.gov/pubmed/8222357 – Step to block seems to be adhesion to human cells Encouraging Healing • Encourage development of fibroblasts, which construct connective tissue, by releasing fibroblast growth factors 1,2,7,10 – In order to avoid disrupting body’s natural healing process, couple FGF generator to a repressor that is activated by fibroblast products (collagens, glycoproteins, etc) Avoiding an Immune Response • PMID: 16771855: interaction of B. infantus and L. salivarius with intestinal cells • PMID: 15260992: toll-like receptors and intestinal bacteria • Toll-like receptors in the induction of the innate immune response – Alan Aderem & Richard J. Ulevitch Containing Immuno-cloaker • Engineer two-step process for generation of protection from immune response – Protein cleavage – Require additional enzyme to effect some conformational change Preventing Spread of Bacteria • Cause bacteria to cut DNA responsible for immuno-cloaker and infection stoppers when not exposed to chemicals characteristic of a wound environment – In vivo detection of secreted proteins from wounded skin using capillary ultrafiltration probes and mass spectrometric proteomics, Chun-Ming Huang, Dr., Chao-Cheng Wang, Stephen Barnes, Craig A. Elmets • Restriction enzymes moderated by a repressor that is activated by eg. thymosin beta 10 and 4 Other Potential Applications • Bacteria that prevent the binding of other bacteria could be used to help patients with a weakened immune system (or injured/sick babies) • Immune-resistant bacteria could be used in any medical application where a bacterium needs to avoid detection – Bacteria that unclog arteries? – Bacteria that produce insulin?
