【AACR Sub-Journal】An important bacterial protein related to colorectal cancer has been discovered, which is expected to develop preventive drugs!

This article was originally written by Translational Medicine.
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Author: Ashley Introduction: In recent years, the prevalence of colorectal cancer has been increasing rapidly.
Recent studies have also found a toxin UshA in bacterial strains that cause common food poisoning symptoms.
It damages DNA in intestinal cells, potentially causing colon cancer
.

This finding raises the possibility of producing drugs to prevent colorectal cancer in the future by neutralizing the newly discovered toxin UshA
.

According to researchers at the Bloomberg School of Public Health, bacterial strains that cause common symptoms of food poisoning often contain a toxin that damages DNA in intestinal cells, potentially triggering colon cancer
.

The finding raises the possibility that some of the roughly 2 million new cases of colorectal cancer worldwide each year stem from brief, seemingly minor episodes of food poisoning
.

It also points to the possibility of producing drugs to prevent colorectal cancer in the future by neutralizing the newly discovered toxin UshA
.

The findings, titled "Bacterial Genotoxin Accelerates Transient Infection-Driven Murine Colon Tumorigenesis," were published in the January issue of Cancer Discovery
.

Previous research has shown that certain bacteria that reside in the gut can trigger colorectal cancer through persistent infections involving chronic intestinal inflammation
.

Short-term infections that cause food poisoning, including traveler's diarrhea, usually resolve within a day or two, and have traditionally been considered non-carcinogenic
.

"We hope this study will inspire other researchers to do epidemiological studies investigating transient diarrheal infections and colon cancer development," said study senior author Fengyi Wan, PhD, associate professor in the Bloomberg School of Public Health's Department of Biochemistry and Molecular Biology.
In the study, Wan's team conducted experiments with a mouse model of transient bacterial diarrheal disease using Citrobacter rodentium, which is associated with the human-infecting microorganism Escherichia coli
.

The diarrhea-causing strains have strong similarities
.

The researchers observed that Citrobacter infection quickly led to strong signs of DNA damage in mouse intestinal cells
.

The scientists also noted that this damage relies on a mechanism in bacteria known as the type 3 secretion system
.

This syringe-like appendage is utilized by some bacteria, including Citrobacter and diarrhea-causing strains of E.
coli, to inject proteins into host cells
.

This mechanism facilitates the growth and survival of invading microorganisms
.

The researchers eventually focused on a T3SS-injecting protein, UshA, that explained DNA damage
.

They found that UshA, also produced by diarrhea-causing E.
coli, contains a short fragment with DNA-breaking enzyme activity
.

The function of this DNA-breaking element in the Citrobacter life cycle is unknown
.

(Deleting it did not appear to impair bacterial growth or survival in studies
.

) But the researchers found evidence in their mouse studies that UshA can have a definitive carcinogenic effect in infected hosts
.

Experimenting with a strain of genetically engineered mice that spontaneously developed colon tumors, the scientists found that infection of these mice with Citrobacter bacteria containing UshA dramatically accelerated tumor development
.

In contrast, infection of engineered Citrobacter bacteria lacking the UshA gene had essentially no effect on accelerating tumor development
.

The researchers also found that the mutation patterns in Citrobacter sp.
accelerated colon tumors were highly similar to those catalogued in human colon tumors, again underscoring the potential relevance to human health
.

Robust confirmation of this correlation isn't easy to accomplish, Wan said, because the transient infection by definition disappears long ago as the tumor progresses
.

(Colon tumors often develop years before they are discovered
.

) Wan believes that establishing a link between UshA-containing microbes and human colorectal cancer will require epidemiological studies
.

These may be best done in sub-Saharan Africa, where bacterial infections that cause diarrhea and colorectal cancer are relatively common, he said
.

Wan is also now working with researchers to develop inhibitors of the UshA toxin
.

"In principle, you could give a patient with diarrheal disease such an inhibitor to protect them from cancer-promoting DNA damage," he said
.

Reference: https://medicalxpress.
com/news/2022-01- bacterial-protein-colorectal-cancers.
html Note: This article is intended to introduce medical research progress and cannot be used as a reference for treatment plans
.

For health guidance, please go to a regular hospital for treatment
.

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