First-in-Human Adjunctive Bacteriophage Therapy for Malakoplakia

Bacteriophages, also known as phages, are specialized viruses that infect bacteria. A key characteristic of phages is their distinctive “head-tail” morphology. A phage begins the infection process (i.e., lytic cycle) by attaching to the outside of a bacterial cell. Attachment is accomplished via proteins in the phage tail that bind to specific receptor proteins on the outer surface of the bacterium. The tail injects the phage’s DNA genome into the bacterial cytoplasm. In the lytic replication...

Bacteriophages are found throughout the human body. They may even outnumber eukaryotic viruses, forming an important and dynamic component of the human virome. Indeed, phages represent the most abundant viral entities, with densities in the gut reaching up to 10⁹ particles per gram of fecal matter, and many belonging to orders such as Caudovirales and Microviridae, while a substantial proportion remains unclassified as viral “dark matter.”Lysogeny and Genetic ExchangeIn the gut, bacteriophages...

In contrast to the lytic cycle, phages infecting bacteria via the lysogenic cycle do not immediately kill their host cell. Instead, they combine their genome with the host genome, allowing the bacteria to replicate the phage DNA along with the bacterial genome. The incorporated copy of the phage genome is called the prophage. Some prophages can re-activate and enter the lytic cycle. This often occurs in response to a perturbation, such as DNA damage, but can also transpire in the absence of...