Bacteria deactivate cancer drugs

Could bacteria be conspiring with cancer to block the action of chemotherapy drugs?
14 September 2017


Pancreatic cancer with resident bacteria (stained for LPS)


Could bacteria living inside tumours be conspiring with cancer cells to block the action of chemotherapy drugs?

According to scientists in Israel, bacteria can get inside tumours, and even inside cancer cells themselves, and then use their own metabolic machinery to break down anti-cancer drugs and protect the tumour.

Ravid Straussman and his team at the Weizmann Institute had originally been looking at why certain types of skin cell appear to be able to protect nearby cancer cells from being wiped out by a chemotherapy drug called gemcitabine. His hypothesis was that the skin cells were secreting something into the surrounding medium that was deactivating the drug or preventing it from working.

To test this he filtered the culture medium to remove anything bacteria-sized or bigger, at which point the protective effect went away. The source of the chemotherapy-blocking effect, he discovered, were small bacteria called Mycoplasma hyorhinis living in and on the skin cells. These - and many other common bacteria, the team have since confirmed - are endowed with metabolic pathways that can break down the gemcitabine drug molecule and prevent it from working. Specifically, bacteria capable of doing this, the team have found, carry a particular form of a gene coding for an enzyme called CDD - cytidine deaminase. This digests gemcitabine, rendering it harmless to a tumour. 

The question is whether this effect makes a difference to the way tumours behave in the body. To explore this, the Israeli team compared mice with tumours that either were or were not colonised with CDD-expressing bacteria; they also dosed groups of mice with antibiotics as well as the gemcitabine chemotherapy drug. Bacteria in the tumours, they found, prevented the animals responding to the chemotherapy. Killing off the bacterial cells, on the other hand, restored the drug sensitivity and the tumours were destroyed.

Whether this effect applies to human patients though, Straussman and his team can't tell yet. "It's difficult to know. Someone needs to do a clinical trial," he says. "But we profiled 113 pancreatic cancers from patients and we found bacteria in the majority of them. Bacteria were found between and even inside cancer cells and they had the ability to break down gemcitabine."

While they are preliminary, the results of the study, out this week in the journal Science, highlight a fertile avenue for further exploration. Is there effectively a relationship forming between cancers and bacteria whereby the tumours recruit the right sorts of bugs that can protect them? And should appropriate antibiotics be included with a chemotherapy regimen to prevent tumours becoming bacterially colonised in this way.

"We'd need to be cautious, though," warns Straussman. "Giving broad-spectrum antibiotics could cause more harm than good under certain circumstances. A better approach might be to develop drugs to block selectively the bacterial metabolism of the anti-cancer drugs."


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