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Much of the time, when scientists think of cancer-causing agents, they think of DNA damage. Indeed, some of the most infamous causes of cancer, such as excessive sunlight, tobacco smoke, or environmental pollutants, act by inducing mutations in key regions of our genes which can lead to effects such as the formation of malignant tumors. However, one lesser-known cause of cancer is slowly but surely becoming a real problem worldwide: bacterial infection. Since our bodies and especially our immune cells are designed to defend aggressively against infection, bacteria have evolved a multitude of survival mechanisms to carry out their life cycles inside of us. While this seems unrelated to cancer it turns out that many of these bacteria, thanks to survival mechanisms such as the release of toxins and effector proteins, can wreak havoc on normal cell processes by damaging DNA. This in turn can lead to the onset of many different malignancies. Here, we will go over some aspects of bacterial infection that can lead to cancer and discuss the importance of coming up with solutions.
The human body is designed in many ways to keep invaders out. There are physical membranes, internal chemical defenses, and also defenses at the immune system level. Successfully growing and surviving within this hostile environment requires clever adaptations.
One example can be found on the surface of Helicobacter pylori. This bacteria is found in a large percentage of the world’s population, where it resides in the digestive system. How might this bacteria increase the risk of cancer? One way has to do with how it latches onto human cells via special surface proteins. A noteworthy consequence of this is inflammation as well as hypergastrinemia, an abnormal production of the gastrin hormone. Both of these conditions are associated with the onset of cancer. Furthermore, a 2011 study found that adhesion of H. pylori can directly lead to double stranded DNA breaks, which is a recipe for possible mutations. Indeed, a variant of H. pylori without a key surface protein known as BabA was found to be significantly less potent at inducing DNA breaks.
Beyond the surface level, some bacteria choose to live intracellular lives, meaning that they are swallowed up by human cells and reside and multiply there. In order to make a home within a cell, the bacteria will inject special proteins called effectors to soften up the host’s defenses. These effectors, while serving to make the cellular environment more bacterial-friendly, have also been found to play a role in cancer development. Take Salmonella for example. You may recognize this genus of intracellular bacteria as a foodborne pathogen. To help it survive inside of our cells, it releases many different types of effectors, with several studies linking these effectors with carcinogenic effects. Notably, mice exposed to Salmonella enterica with a full effector arsenal developed colon carcinoma, whereas the same mice exposed to an effector-free variety did not develop any cancer.
Infectious disease and the rising rates of antibiotic resistance is a growing problem we cannot continue to ignore. As the above examples illustrate, it’s naïve to hope that cancer can be beaten while ignoring bacterial diseases. H. pylori infection in general is reported to be the single strongest risk factor in gastric (stomach) cancer. This has tremendous significance as, according to the World Health Organization, worldwide gastric cancer is the third highest cause of cancer deaths. Due to the sheer number of individuals in the world who are infected with H. pylori, we have a major opportunity to tackle a chronic bacterial infection while also rooting out a source of cancer at the same time. Unfortunately, many companies see antibiotic research as a financial loser, as the resources needed to develop new medications are perceived to be too large compared to the potential market. But short-term thinking is sure to raise the stakes and only make the problem worse down the road. The best time to invest in antibiotic research was yesterday – who’s going to step up?
Edited by MaryAnn Bower
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