How Cholera Bacteria Defend Against Viruses

Cholera outbreaks are often associated with contaminated water and vulnerable populations, but the bacteria responsible—Vibrio cholerae—are also engaged in a constant battle with bacteriophages, viruses that prey on bacteria. These phages not only affect individual infections but can influence the scale of entire epidemics by killing off V. cholerae. However, the bacteria have evolved mechanisms to defend themselves, sometimes carrying mobile genetic elements that provide anti-viral tools.

The ongoing seventh cholera pandemic, driven by “seventh pandemic El Tor” (7PET) strains since the 1960s, has seen bacteria and phages locked in an evolutionary arms race. Notably, in the early 1990s, an epidemic in Peru and Latin America, caused by the West African South American (WASA) lineage of V. cholerae, infected over a million people. The reasons for the WASA strains’ success in causing such a large outbreak have been unclear.

Recent research led by Melanie Blokesch’s group at EPFL’s Global Health Institute, published in Nature Microbiology, has identified that the WASA lineage acquired several distinct bacterial immune systems, providing protection against various phages. The study found that Peruvian WASA strains from the 1990s were immune to the dominant phage ICP1, unlike other 7th pandemic strains.

By analyzing the WASA genome, researchers discovered two major defense regions: WASA-1 prophage and Vibrio seventh pandemic island II (VSP-II). These encode anti-phage systems such as WonAB, which induces abortive infection—sacrificing infected cells to prevent phage spread. Other systems, GrwAB and VcSduA, target phages with modified DNA and different virus families, respectively, broadening the bacteria’s resistance.

This expanded anti-phage arsenal may have contributed to the WASA lineage’s epidemic potential. Understanding these defenses is important, especially as interest in phage therapy grows, highlighting the need to consider phage-bacteria interactions in cholera control and treatment strategies.