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?