Phage Therapy: Meeting the Challenge of Drug-Resistant Bacterial Infections

Global pandemics, such as COVID-19, have taught us to abhor viruses. The emergence of new, highly infectious viruses is—rightfully so—a cause for concern. However, despite the average human body harboring 380 trillion viruses, most of them simply coexist with us and are harmless. When it comes to an ancient lineage of viruses within the realm Duplodnaviria, researchers are even using them as weapons in the battle against infectious diseases.

In 1915, Frederick William Twort, an English bacteriologist at the University of London, reported the discovery of an unusual “ultramicroscopic virus” (1). Twort was culturing vaccinia virus as part of an experiment to determine if he could prepare smallpox vaccines in vitro. These vaccines, made in calves, were typically contaminated with Staphylococcus bacteria. When Twort plated the vaccines, he found small, clear areas on the agar plates where the bacteria would not grow, and these clear areas were the source of his ultramicroscopic virus. Two years later, a French-Canadian microbiologist, Félix d’Hérelle, independently discovered a similar phenomenon when culturing Shigella bacteria from fecal samples of patients with bacillary dysentery. He called the new virus “un bactériophage obligatoire” (2). Shortly after his discovery, he found that bacteriophages (phages) could be used as powerful agents to treat a variety of bacterial infections, and the field of phage therapy was born (3).

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Hope for Treatment of Carbapenem-Resistant Bacteria

Structure of the antibiotic meropenem
Structure of the antibiotic meropenem
Last month brought some hopeful news on the subject of antibiotic resistance. A paper published in Nature on June 26 described the isolation of a fungal compound that restored the antibiotic sensitivity of carbapenem-resistant enterobacteria. An editorial accompanying the paper took encouragement from the article–considering it a sign that the well of potential sources of new antimicrobial agents, and agents that inhibit resistance mechanisms, is not yet dry:

But the reservoir of natural products with the potential to act as antibacterial drugs has not yet been exhausted. In contrast to general thinking by drug companies, screening for such products may well still have a bright future” Nature News and Views: “Antibiotic resistance: To the rescue of old drugs” Meziane-Cherif & Courvalin, Nature 510, 477–478.

The emergence of bacteria that are resistant to antibiotics has been an object lesson in the relentlessness of natural selection; the moment a new antibiotic is developed and introduced, the countdown to the emergence of resistance begins. The race to keep the one step ahead of emerging resistance mechanisms has been going on since antibiotics were first introduced.

The history of the development of penicillin and related antibiotics is both an illustration of the ingenuity of scientists and of the never-ending nature of this battle with emerging resistance. The Nature paper is the latest installment in that story. Continue reading “Hope for Treatment of Carbapenem-Resistant Bacteria”

Making Antibiotics More Effective Against Multidrug-Resistant Bacteria

The Age of Antibiotics may prove to be our downfall as more and more microbes find a way around the compounds we use to treat bacterial infections. A potential antibiotic is no more tested, synthesized, clinically tested and approved than a bacterial strain finds a way to circumvent its action and shares this solution with other bacteria. While physicians are becoming more concerned about the lack of new antibiotics in their arsenals to treat patients with methicillin-resistant Stapholococcus aureus (MRSA) or other multidrug-resistant (MDR) bacteria, researchers are exploring alternative means to fight MDR microbes that can devastate human health. In Maryn McKenna’s book Superbug, Dr. Robert Daum advocated producing a vaccine against MRSA to prevent infection rather than lose the antibiotic battle during treatment (see the Nature News article on the same subject). Some scientists are rethinking bacteriophages and their use. A team of researchers at North Carolina State University discovered another option:  A small molecule that attenuates the antibiotic resistance in Klebsiella pneumonia. Continue reading “Making Antibiotics More Effective Against Multidrug-Resistant Bacteria”