Bacteria-killing virus is used to treat drug-resistant disease in immunocompromised patients

The predator at the top of the microbial world is a virus known as a phage. It hunts and destroys bacteria by hijacking the microorganism’s reproductive machinery and tearing it apart. As a result, scientists have commanded these microscopic killers to fight on the front lines of a growing threat: antibiotic resistance, or when bacteria find a way around drugs to stop them.

A 2019 global survey found that more people die from antibiotic resistance than from HIV/AIDS or malaria. We have even seen a rapid increase in drug-resistant gonorrhea, Salmonella, among many others in recent years. Equally worrisome is the rise in drug resistance Mycobacterium chelonae—A bacterium similar to the bacteria that causes diseases like tuberculosis and leprosy — threatens immunocompromised people and is a major public health concern.

That’s where bacteria come in. Boston researchers used a viral therapy to successfully treat a man with drug resistance M. chelonae infections, according to a new study published Tuesday in the journal Nature. The infection belongs to a group of mycobacteria called nontuberculous bacteria, which are considered the most drug-resistant of the group — and therefore, one of the most difficult to treat.

Dr. Jessica Little, an internist at Brigham Women’s Hospital and first author of the study, told The Daily Beast in an email: “There is a long history of actinomycete therapy for many types of bacterial infections. “This [study] was the first instance of phage therapy to treat a specific organism and the first instance of a single phage rather than a cocktail [of bacteriophages] used to treat non-tuberculosis bacteria. “

This bacterium is commonly found in water and soil. In general, they are quite harmless – that is, until these microorganisms enter the human body through contaminated drinking water or a wound in the skin. According to NYU Langone Health, this nasty pathogen causes serious infections in the skin, soft tissues (such as cartilage, fat, muscles, and tendons), and even the lungs. It doesn’t affect everyone, but if you have an underlying health condition like a weakened immune system, you’re at a much higher risk. For these patients, conventional antibiotics are not very helpful because the stubbornly resistant mycobacteria are rapidly evolving to overthrow modern medicine.

But that doesn’t mean it’s invincible. In the past, scientists have used bacteria designed to treat lung infections caused by Mycobacterium abscessusThis inspired Little and her team to study whether a similar approach could be used to treat close relatives of bacteria. M. chelonae.

The key to this is finding the right bacteria. Like a picky eater, macrophages have several types of bacteria they like to eat. Fortunately, scientists have developed centralized libraries and databases of bacteria. One such effort is through the Science Education Alliance-Phage Hunters Alliance to Advance Genomics and Evolutionary Sciences (SEA-PHAGES) initiative, which to date has isolated and cataloged more than 20,000 phages are found in nature.

Little and her team submitted a sample M. chelonae were collected from their patient, a 45-year-old man with rheumatoid arthritis caused by an autoimmune disease, to Graham Hatfull at the University of Pittsburgh, whose lab co-supervised SEA-PHAGES and also studied phagocytosis of mycobacteria. After rounds of testing, a promising candidate emerged: a phage named Muddy.

Armed with the right phage, the researchers grew a lot and gave it to their patients through an IV drip method. The man did not improve with antibiotics and even after undergoing surgery to remove infected skin lesions from M. chelonae. But within a few months of having Muddy injected into his vein, the man’s painful skin lesions shrunk, eliminating bacteria without any negative side effects.

It is the first promising approach to treating specific antibiotic-resistant infections with a specific type of bacteria rather than entire types of phages, which is the way therapy is often given to strengthen the immune system. Its powerful bacteria kill. The wholesale method can allow bacteria to actually become resistant to bacteriophages. However, Little cautions that this is just one case study with one patient. “Clinical trials are needed to better understand the benefits of phage therapy on a larger scale and in a more controlled environment,” she said.

Scientists also don’t have a complete picture of how actinomycete therapy works at the immune system level and the potential risks. To date, clinical trials with patients have been generally safe with not many negative side effects reported. But it is not easy to identify the right phage for the right disease. Producing this therapy on a commercial scale is also a challenge. Still, Little believes it’s important that researchers build on the study to help improve treatments for the most vulnerable patients.

“Resistance is a serious and growing threat globally and phage therapy is a promising new treatment option for the treatment of these infections,” Little said. “There are an amazing number of different phages that can treat unique bacteria – this is precision medicine and it is very complex – but I believe that developing antibiotic-free strategies, focusing on Focusing on pathogens to complement the tools we already have is very important. This moment. ”