Bermudes Lab discovery could aid in engineering cancer-fighting bacteria

Bacteria engineered to produce and deliver drug compounds could be a new powerful new tool for cancer therapy and many other medical applications. A new paper from CSUN microbiologists may offer a solution to a key problem with bacteria-delivered drugs — preventing the drug compounds from breaking down before they can take effect.

Quintero et al. (2018), Figure 5” class=”wp-image-423″ width=”266″ height=”279″/>
An anticancer drug (A, top), kills most tumor cells in the absence of a proteolytic compound (B, bar 3), but has no effect when the compound is present (B, bar 4); while a version of the drug with an added protease-inhibiting structure (A, lower) restores the drug’s effectiveness (B, bar 5). Quintero et al. (2018), Figure 5

Many of the environments in which drug-delivering bacteria might be used are proteolytic, with conditions that break down many possible drug compounds. This is an obstacle to the effectiveness of therapeutic proteins secreted by bacteria. The Bermudes Lab, together with CSUN students David Quintero, Jamie Carrafa and Lena Vincent who have now graduated, and colleagues at UCLA, have generated and assessed a chimeric, secreted protease inhibitor — incorporating a protein structure that can prevent proteolytic activity into the molecular makeup of an anticancer drug. They found that a therapeutic chimeric toxin was protected from proteolytic degradation when co-expressed with the protease inhibitor and retained the ability to kill cancer cells in laboratory tests.

The full study is online ahead of publication in The Journal of Microbiology and Biotechnology.