Two DNA defense systems behind resilience of 7th cholera pandemic

Strains that cause cholera pandemics have acquired pathogenicity islands through a process known as"", by which bacteria share genes both within and across species. Horizontal gene transfer is a powerful driver of bacterial evolution because it can quickly endow bacteria with new abilities that help them adapt and survive. But it is also indiscriminate, passing on genes that are unnecessary or even harmful to their new host.

Horizontal gene transfer often involves plasmids—self-replicating circular pieces of DNA found in bacteria that can carry up to hundreds of genes. But strains of V. cholerae that are causing the currently ongoing 7pandemic of cholera only rarely carry plasmids while plasmids are abundant in related strains isolated from the environment instead of patients.

This surprising phenomenon caught the attention of scientists at EPFL, who decided to look into it."We wanted to find out why plasmids are so rare in the 7pandemic clade of V. cholerae, shedding light on how bacterial pathogens evolve," says Professor Melanie Blokesch who led the study with Milena Jaskólska and David W. Adams at EPFL's School of Life Sciences.First, the researchers introduced a small model plasmid into V.

This second system turned out to have a much broader role in bacterial defense. Not only can it enhance the elimination of small plasmids, but it can turn against the, degrading its DNA and triggering a form of cell suicide. Essentially, DdmABC protects bacterial population against viruses by killing infected cells before the virus has time to replicate and spread.

The team also found that DdmABC targets large plasmids that often carry huge arrays of antibiotic-resistance genes, and can persist by jumping from one bacterium to the next, spreading multidrug resistance."This finding might explain why the recent pandemic strains mainly carry antibiotic resistance integrated in their genome and not on plasmids," says Blokesch.in the 7pandemic V. cholerae strains," say the researchers.

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