Genetic bottlenecks help explain which cholera strains become pandemic pathogens

A new study highlights one of the great puzzles of microbiology: why only certain strains of common bacteria become pandemic pathogens.

The work, published in Proceedings of the National Academy of SciencesFocus on Vibrio Cholerae, the bacteria that causes cholera. It reveals that its most dangerous form comes from a specific combination of allelic genes and variants which give it an advantage in the human intestine. This research could open the way to new strategies to predict and prevent future cholera epidemics.

The study results from a collaboration between Miguel Hernández University of Elche (UMH), researcher Mario López Pérez and Professor Salvador Almagro-Moreno du St. Jude Children’s Research Hospital. He also involved Professor José M. Haro Moreno of the UMH and the predoctoral researcher Alicia Campos López, affiliated with the Department of Factory and Microbiology production.

Thanks to an in -depth analysis of more than 1,840 Genomes V. Cholerae, the researchers identified eleven distinct phylogenetic clusters, the pandemic group belonging to the largest and located in a line shared with environmental strains.

Their results suggest that the emergence of pandemic stumps, responsible for global cholera epidemics, largely depends on the acquisition of clusters of unique modular genes and allelic variations which allow a competitive advantage during intestinal colonization. These act as non-linear filters that prevent most environmental strains from becoming human pathogens.

“Consequently, only a small group of strains of Vibrio Cholerae can cause cholera in humans, despite the great natural diversity of the species,” explains the UMH researcher, Mario López, the main author of the study. “We wondered why only this little subset had never triggered pandemics.”

The study reveals that the emergence of pandemic clones of V. Cholerae is limited by specific genetic strangulation. These require: a genetic background pre-adapted to virulence, the acquisition of clusters of key genes such as CTXφ and VPI-1, their organization in specific modular arrangements, and finally, the presence of unique allelic variants.

“It is only when all these elements come together that a strain can evolve into a pathogen capable of pandemic,” explains the researchers.

These characteristics are absent in most environmental strains of V. Cholerae and seem to give pandemic clones a key competitive advantage: an improved capacity to colonize the human intestine.

“Interestingly, the genetic features that allow V. Cholerae to infect humans do not benefit bacteria in their natural aquatic environment,” notes López. In nature, V. Cholerae generally lives freely or in association with the colonies, molluscs or crustaceans of cyanobacteria.

Cholera is endemic in certain parts of the world with bad water, sanitation and hygiene infrastructure. Epidemics can also occur after natural disasters that disrupt these systems. The disease is characterized by sudden and serious episodes of aqueous diarrhea, resulting in rapid dehydration and, if it is not treated, potentially death.

“Our analytical model could be applied to other environmental bacteria to understand how the emerging pathogenic clones of non -pathogenic populations”, underlines López.

The study also opens the door to more precise surveillance of strains with a pandemic potential – an approach that could be very useful for future preparation for public health.