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Microbial Cocoon Helps Cells Penetrate, Shrink Tumors

A tour-de-force in bacterial engineering for cancer therapy.

Case Study

Transmission electron microscope images show a sugar coat, or cocoon, wrapped around a cell’s outer surface. Deleting a gene called kfiC causes the shell to disappear. Harimoto, T. et al. A programmable encapsulation system improves delivery of therapeutic bacteria in mice. Nat Biotechnol (2022).

Guilty by Association

Finding a Target

Controlled Cocoon

a, Circuit diagram of the “sugar coat” on-off switch. A small molecule, IPTG, blocks lacI expression, which turns on a gene that helps produce CAP. b, Turning on the ‘cloak’ with more IPTG results in a thicker sugar shell. c, Circuit dynamics for ‘on’ and ‘off.’ The cells are fully surrounded by sugar after about six hours, and the shell disappears in a similar amount of time. Harimoto, T. et al. Nat Biotechnol (2022).

Cancer Payloads

(Left) Bacteria with the sugar shell have reduced immunogenicity in cancer mouse models. The sugar shells reduce initial inflammation while effectively clearing bacteria over time. (Right) Turning on the CAP system causes cells at one tumor to translocate to another tumor. Harimoto, T. et al. Nat Biotechnol (2022).
  1. This experiment, in my opinion, suggests a secondary application for bacterial cocoons. Under normal circumstances, bacteria are swiftly killed by white blood cells. With a protective coat, bacteria can survive for several hours. Could protected bacteria, then, be used to metabolize and remove contaminants in human blood samples, say, before a transfusion? Staphylococcus bacteria are the most common contaminants in blood products, according to the CDC. Perhaps bacteria could be engineered to don their cocoon, destroy the Staphylococcus, and then remove their shell. This might help to keep valuable blood donations from going to waste.



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