Antibiotic Resistance Through Bacterial Genes Inhibiting Viral Reproduction

Antibiotic resistance is a growing global health threat—one that could surpass cancer in mortality within just a few decades. Researchers at Umeå University in Sweden have uncovered a surprising contributor to this problem: the very way bacteria defend themselves against viruses. Specifically, the team found that resistance may stem from bacterial genes that block viruses from reproducing.

One promising approach to addressing antibiotic resistance involves using viruses, known as bacteriophages or phages, to target and kill bacteria. However, the bacterial defense systems that neutralize phages remain poorly understood. Gaining insight into these mechanisms could open new pathways for weakening bacterial defenses—making it possible to treat infections that have become difficult or impossible to cure with current antibiotics.

“We now understand better how resistant bacteria defend themselves against viruses,” said Ignacio Mir-Sanchis, the study’s lead author and an assistant professor at Umeå University. “Understanding these systems may help us find ways to break down bacterial defenses and treat serious infectious diseases in the future.”

The team focused on Staphylococcus aureus, a common bacterium that can cause life-threatening conditions such as septic shock and pneumonia. A subset of S. aureus has developed resistance to multiple antibiotics, creating a major public health concern. In some countries, up to 25% of S. aureus strains are now multi-resistant. In Sweden, the figure remains comparatively low at just 1%.

Phages and bacteria have co-evolved in a continuous arms race—phages attempt to infect, while bacteria evolve to fight back. Much of this bacterial defense is housed in a part of the genome called the mobilome, which is easily shared between bacteria. This genetic transfer can turn otherwise harmless strains into dangerous ones, as the mobilome often carries genes responsible for both antibiotic resistance and toxin production.

Using cryoelectron microscopy, the Umeå team identified a specific set of genes within the S. aureus mobilome that offer protection against phages. These genes work by disrupting the phage’s ability to replicate and spread. One gene produces a protein that forms a protective shell around a key phage protein, effectively blocking the phage from copying its DNA and infecting other bacterial cells.

“The discovery of this mechanism could be a door opener to understand several aspects of bacterial pathogenesis,” Mir-Sanchis noted. “Because these genes also encode for toxins and antibiotic resistance, this may be an important piece of the puzzle in the fight against antibiotic resistance.”