Bug drugs: bacteria-based cancer therapies are finally overcoming barriers

Justin Stebbing, Anglia Ruskin University

Imagine a world where bacteria, typically feared for causing disease, are turned into powerful weapons against cancer. That’s exactly what some scientists are working on. And they are beginning to unravel the mechanisms for doing so, using genetically engineered bacteria to target and destroy cancer cells.

Using bacteria to fight cancer dates back to the 1860s when William B. Coley, often called the father of immunotherapy, injected bacteria called streptococci into a young patient with inoperable bone cancer. Surprisingly, this unconventional approach led to the tumour shrinking, marking one of the first examples of immunotherapy.

Over the next few decades, as head of the Bone Tumour Service at Memorial Hospital in New York, Coley injected over 1,000 cancer patients with bacteria or bacterial products. These products became known as Coley’s toxins.

Despite this early promise, progress in bacteria-based cancer therapies has been slow. The development of radiation therapy and chemotherapy overshadowed Coley’s work, and his approach faced scepticism from the medical community.

However, modern immunology has vindicated many of Coley’s principles, showing that some cancers are indeed very sensitive to an enhanced immune system, an approach we can often capture to treat patients.

How bacteria-based cancer therapies work

These therapies take advantage of the unique ability of certain bacteria to proliferate inside tumours. The low oxygen, acidic and dead tissue in the area around the cancer – the tumour “microenvironment” (an area I am especially interested in) – create an ideal niche for some bacteria to thrive. Once there, bacteria can, in theory, directly kill tumour cells or activate the body’s immune responses against the cancer. However, several difficulties have hindered the widespread adoption of this approach.

Safety concerns are paramount because introducing live bacteria into a patient’s body can cause harm. Researchers have had to carefully attenuate (weaken) bacterial strains to ensure they don’t damage healthy tissue. Additionally, controlling the bacteria’s behaviour within the tumour and preventing them from spreading to other parts of the body has been difficult.

Bacteria live inside us, known as the microbiome, and treatments, disease and, of course, new bacteria that are introduced can interfere with this natural environment. Another significant hurdle has been our incomplete understanding of how bacteria interact with the complex tumour microenvironment and the immune system.

Questions remain about how to optimise bacterial strains for maximum anti-tumour effects while minimising side-effects. We’re also not sure of the dose – and some approaches give one bacteria and others entire colonies and multiple bug species together.

Recent advances

Despite these challenges, recent advances in scientific fields, such as synthetic biology and genetic engineering, have breathed new life into the field. Scientists can now program bacteria with sophisticated functions, such as producing and delivering specific anti-cancer agents directly within tumours.

This targeted approach could overcome some limitations of traditional cancer treatments, including side-effects and the inability to reach deeper tumour tissues.

Emerging research suggests that bacteria-based therapies could be particularly promising for certain types of cancer. Solid tumours, especially those that have a poor blood supply and are resistant to conventional therapies, might benefit most from this approach.

Colon cancer, ovarian cancer and metastatic breast cancer are among the high-mortality cancers that researchers are targeting with these innovative therapies. One area we have the best evidence for is that “bug drugs” may help the body fight cancer by interacting with routinely used immunotherapy drugs.

Recent studies have shown encouraging results. For instance, researchers have engineered strains of E coli bacteria to deliver small tumour protein fragments to immune cells, effectively training them to recognise and attack cancer cells. In lab animals, this approach has led to tumour shrinkage and, sometimes, complete elimination.

By exploiting these mechanisms, bacterial therapies can selectively colonise tumours while largely sparing healthy tissues, potentially overcoming limitations of conventional cancer treatments.

Ultimately, we need human trials to give us the answer about whether this works, by controlling or eradicating cancer and, of course, if there are side-effects, its toxicity.

In one study I worked on, we showed that part of a bacterial cell wall, when injected into patients, could safely help control melanoma – the most deadly form of skin cancer.

While we’re still in the early stages, the potential of bacteria-based cancer therapies is becoming increasingly clear. As our understanding of tumour biology and bacterial engineering improves, we may be on the cusp of a new era in cancer treatment.

Bacterial-based cancer therapies take advantage of several unique mechanisms to specifically target tumour cells. As a result, these therapies could offer a powerful new tool in our arsenal against cancer, working in synergy with existing treatments like immunotherapy and chemotherapy. And, as we look to the future, bacteria-based cancer therapies represent a fascinating convergence of historical insight and groundbreaking science.

While challenges remain, the progress in this field offers hope for more effective, targeted treatments that could significantly improve outcomes for cancer patients.

Justin Stebbing, Professor of Biomedical Sciences, Anglia Ruskin University

This article is republished from The Conversation under a Creative Commons license. Read the original article.

Read More........→March 24, 2025

This Common Fungus Found on Human Skin Wipes Out Deadly Superbug Staph Infections

University of Oregon researchers have uncovered a molecule produced by yeast living on human skin that showed potent antimicrobial properties against a pathogen responsible for a half-million hospitalizations annually in the US.

It’s a unique approach to tackling the growing problem of antibiotic-resistant bacteria. With the global threat of drug-resistant infections, fungi inhabiting human skin are an untapped resource for identifying new antibiotics, said Caitlin Kowalski, a postdoctoral researcher at the UO who led the study.

Described in a paper published last month in Current Biology, the common skin fungus Malassezia gobbles up oil and fats on human skin to produce fatty acids that selectively eliminate Staphylococcus aureus.

One out of every three people have Staphylococcus aureus harmlessly dwelling in their nose, but the bacteria are a risk factor for serious infections when given the opportunity: open wounds, abrasions and cuts. They’re the primary cause of skin and soft tissue infections known as staph infections.

Staphylococcus aureus is also a hospital superbug notorious for being resistant to current antibiotics, elevating the pressing need for new medicines.

There are lots of studies that identify new antibiotic structures, Kowalski said, “but what was fun and interesting about ours is that we identified (a compound) that is well-known and that people have studied before.”

The compound is not toxic in normal lab conditions, but it can be potent in conditions that replicate the acidic environment of healthy skin. “I think that’s why in some cases we may have missed these kinds of antimicrobial mechanisms,” Kowalski added, “because the pH in the lab wasn’t low enough. But human skin is really acidic.”

Humans play host to a colossal array of microorganisms, known as the microbiome, but we know little about our resident fungi and their contributions to human health, Kowalski said. The skin microbiome is of special interest to her because while other body parts crowd dozens of different fungi, the skin is dominantly colonized by one kind known as Malassezia.

Malassezia can be associated with cases of dandruff and eczema, but it’s considered relatively harmless and a normal part of skin flora. The yeast has evolved to live on mammalian skin, so much so that it can’t make fatty acids without the lipids—oils and fats—secreted by skin.

Despite the abundance of Malassezia found on us, they remain understudied, Kowalski said.

“The skin is a parallel system to what’s happening in the gut, which is really well-studied,” she said in a media release. “We know that the intestinal microbiome can modify host compounds and make their own unique compounds that have new functions. Skin is lipid-rich, and the skin microbiome processes these lipids to also produce bioactive compounds. So what does this mean for skin health and diseases?”

Looking at human skin samples from healthy donors and experiments done with skin cells in the lab, Kowalski found that the fungal species Malassezia sympodialis transformed host lipids into antibacterial hydroxy fatty acids. Fatty acids have various functions in cells but are notably the building blocks for cell membranes.

The hydroxy fatty acids synthesized by Malassezia sympodialis were detergent-like, destroying the membranes of Staphylococcus aureus and causing its internal contents to leak away. The attack prevented the colonization of Staphylococcus aureus on the skin and ultimately killed the bacteria in as little as 15 minutes, Kowalski said.

But the fungus isn’t a magic bullet. After enough exposure, the staph bacteria eventually became tolerant to the fungus, as they do when clinical antibiotics are overused.

Looking at their genetics, the researchers found that the bacteria evolved a mutation in the Rel gene, which activates the bacterial stress response. Similar mutations have been previously identified in patients with Staphylococcus aureus infections.

The findings show that a bacteria’s host environment and interactions with other microbes can influence its susceptibility to antibiotics.

“There’s growing interest in applying microbes as a therapeutic, such as adding bacteria to prevent the growth of a pathogen,” Kowalski said. “But it can have consequences that we have not yet fully understood. Even though we know antibiotics lead to the evolution of resistance, it hasn’t been considered when we think about the application of microbes as a therapeutic.”

While the discovery adds a layer of complexity for drug discovery, Kowalski said she is excited about the potential of resident fungi as a new source for future antibiotics.

Identifying the antimicrobial fatty acids took three years and a cross-disciplinary effort. Kowalski collaborated with chemical microbiologists at McMaster University to track down the compound.

“It was like finding a needle in a haystack but with molecules you can’t see,” said Kowalski’s adviser, Matthew Barber, an associate professor of biology in the College of Arts and Sciences at the UO.

Kowalski is working on a follow-up study that goes deeper into the genetic mechanisms that led to the antibiotic tolerance. She is also preparing to launch her own lab to further investigate the overlooked role of the skin microbiome, parting from Barber’s lab after bringing fungi into focus.

“Antibiotic-resistant bacterial infections are a major human health threat and one that, in some ways, is getting worse,” Barber said. “We still have a lot of work to do in understanding the microorganisms but also finding new ways that we can possibly treat or prevent those infections.”[Source: By Leila Okahata, University of Oregon] This Common Fungus Found on Human Skin Wipes Out Deadly Superbug Staph Infections

Read More........→June 06, 2025