One of the compounds found in bloodroot is called sanguinarine. Researchers focused on two sanguinarine derivatives that specifically impacted mycobacteria, the bacteria genus that includes tuberculosis.

Image Credit: WIKIMEDIA COMMONS/Ryan Hodnett

Researchers at the University of British Columbia are using a North American wildflower called bloodroot — long used by First Nations in traditional medicine — to fight drug-resistant tuberculosis.

In test tubes, researchers have found that low doses of two compounds taken from the wildflower’s root inhibited the growth of the bacteria that cause multidrug-resistant TB, commonly known as antibiotic-resistant TB, by more than 90 per cent.

While the research is still in the very early stages, these compounds could one day be used as new antibiotics to fight TB, said Yi Chu Liang, a University of Ottawa doctoral student and visiting PhD student at UBC.

TB is the leading cause of bacterial disease-related death worldwide, and the treatment of it hasn’t changed much in the last 50 years, Liang said.

A research article on Liang’s work on bloodroot with Jim Sun, an assistant professor in the UBC department of microbiology and immunology and senior author of the paper, was recently published in the journal Microbiology Spectrum.

New treatments for TB are badly needed because the current method requires patients to undergo many months of treatment, taking four different antibiotics to clear the infection, the study noted. Plus, antibiotic-resistant TB is on the rise.

TB is caused by a common bacterium that belongs to the Mycobacterium genus. One in four people will be infected in their lifetime, Liang said.

But being infected with the bacteria is not the same as having the disease, said Sun.

When a person is exposed to TB, their immune system can do one of three things: fight off the bacteria and “clear” the infection; keep the infection in an inactive state within the body, known as a latent infection; or fail to fight it off. In the latter case, the person becomes infected with “active TB,” where they feel sick and are contagious, according to Health Canada.

Health Canada says TB is infectious only during active infection, or when a person feels sick. Symptoms can include fever, a cough lasting more than two weeks, coughing up phlegm or blood, chest pain and a lack of appetite. The bacterium is passed on when an infectious person coughs, sneezes or sings near an uninfected person.

The World Health Organization says around 1.3 million people died from TB in 2022, and that TB kills more people than HIV-AIDS. Multidrug-resistant TB “remains a public health crisis and health security threat,” the WHO said.

During the height of the COVID-19 pandemic, COVID was the deadliest pathogen out there, but TB has since taken back its grim title, Liang said.

In the general Canadian population, between four and five people per 100,000 get TB, Sun said. But for Indigenous populations that jumps to 150 per 100,000, and Inuit communities are 200 to 300 times more susceptible to TB than the general population, he added.

TB rates in remote Indigenous communities in Canada can be similar to TB rates in countries such as South Africa, India and China where the disease is endemic, Sun said.

“It’s part of why society has forgotten about TB,” Sun said. “If you’re in a privileged part of the world, you don’t hear about it as much. But in other parts of the world, it’s as bad as COVID was during the peak of the pandemic.”

Patients with active TB have to take four antibiotics, usually isoniazid, rifampicin, pyrazinamide and ethambutol, for six months. These antibiotics “are harsh on the body” and can cause nausea, vomiting, diarrhea and pain, Liang said.

The treatment takes so long because even if 90 per cent of the active infection is killed, there may be 10 per cent lying dormant, and a patient needs to take the antibiotics until a doctor can determine there is no more dormant infection, Sun said. Another goal of TB research is to shorten the treatment time, which could help reduce the side-effects of the medications, he said.

A patient might start feeling better after a couple of weeks but needs to take the medications for the entire prescribed period, Liang said. He added that antibiotics generally attack bacteria when they are multiplying, so it’s hard to treat an infection if it’s dormant.

Once a disease gets into a remote community, it can be really hard to clear it, Sun said.

This is for several reasons. To start, the historical and ongoing impacts of colonialism can mean Indigenous communities have poor-quality and crowded housing, malnutrition and higher rates of smoking and drinking, which are all associated with TB, Sun said.

There also seem to be genetic or epigenetic reasons that make Indigenous people more susceptible to the disease even after other socio-economic factors have been accounted for, he said.

The remoteness of some communities can also mean people don’t have the same ability to access a doctor or clinic that could provide diagnosis and treatment, he said. After a person clears an infection, they can be reinfected, he added.

Sun said there is a strategy in Canada to send teams of doctors to remote communities to help diagnose and treat TB, but after a couple of years cases can spike once again.

Which is why it’s so exciting to find new compounds that can potentially fight multidrug-resistant TB, Liang said.

History of bloodroot in fighting tuberculosis

This wouldn’t be the first time bloodroot has been used to fight TB.

According to one 2016 paper, people of the Algonquian, Iroquois and Siouan language groups had a range of uses for the wildflower, including to treat colds and congestion, as a lozenge for sore throats and to treat diphtheria and hemorrhagic tuberculosis.

A small piece of the root would be added to a concoction because larger doses would cause poisoning, the paper said.

One of the compounds found in bloodroot is called sanguinarine, which researchers broke into 35 derivatives. They focused on two that specifically impacted mycobacteria, the bacteria genus that includes TB.

The two derivatives seem to impact mycobacteria and leave other bacteria alone, Liang said.

“This is good, because if you have an antibiotic that is more specific to the thing you want to go after, it means that it might be less harsh on your other bacteria,” he added. “For example, the bacteria you have in your gut, which play a role in maintaining our health.”

The research found these two derivatives inhibit the growth of three aggressive strains of TB and five strains resistant to several current antibiotic treatments. When tested on mice infected with a weakened form of animal TB, the derivatives reduced the amount of bacteria present in the lungs within eight days.

The derivatives also seem to be able to “keep hibernating bacteria sleeping or prevent it from waking up,” Liang said. This could reduce the chances of an infected person ever developing the disease, he added.

It’s difficult to develop antibiotics in general, especially for TB-causing bacteria, said Thomas Dick, a member of the Center for Discovery and Innovation in New York and a professor at the Hackensack Meridian School of Medicine in New Jersey and Georgetown University in Washington, D.C.

Dick, who was not involved in the study, said drug resistance will always emerge when fighting bacteria, and the only solution is to develop new drugs. There has been some progress, with drugs like bedaquiline and pretomanid being approved and new drug combinations being used to fight TB, but there is a need to keep feeding the research pipeline that develops these drugs, he said.

For these derivatives to one day be made into TB drugs, they will have to be shown to fight drug-resistant strains, work in cells and in animals, work against non-replicating or dormant forms of TB, and harm only TB and leave good bacteria alone, Sun said.

The “ideal compound” would have all four attributes. “Our compounds kind of satisfy a lot of those, which is unique,” Sun added. “Obviously there’s a lot more work to be done... but it’s an exciting start.”

Next, Liang said, the team wants to test more animal models with normal TB and multidrug-resistant TB to get a better understanding of how the compounds work and what they target in the TB-causing bacteria. This will help the team know how to make the compounds less toxic for the overall human system, more effective and “overall more suitable as a drug,” he said.

He added that he hopes this discovery will help spread awareness about TB and how it is getting harder and harder to treat because of antibiotic resistance.

“If we have more awareness, hopefully that can lead to more funding and more research being done so we can come up with new tools to fight TB,” he said. “At this point every little bit counts.”

— This story was originally published by The Tyee.

News from © iNFOnews, 2024