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Genomic Study of Argentinian Cholera Outbreak Finds Differences Between Endemic, Epidemic Bacteria

NEW YORK – A single epidemic Vibrio cholerae strain introduced into Argentina sparked a cholera outbreak there in the 1990s, a new sequencing analysis has found.

Seven cholera pandemics have swept the globe since the 1800s, and the current one, caused by a lineage dubbed 7PET, began in the 1960s. In 1991, an outbreak made its way to Argentina, which had not experienced a cholera epidemic for 96 years.

An international team of researchers has now sequenced nearly 500 cholera samples collected during the years-long outbreak to better understand how the epidemic strain spread and to investigate local, endemic strains. As they reported in Nature Communications on Thursday, the researchers found that a single clone of the epidemic 7PET strain was behind the Argentinian outbreak and that this genetically invariable strain circulated alongside more changeable endemic V. cholerae strains.  

"When a 7PET pandemic strain enters into Latin America from elsewhere, it can cause massive epidemics, such as those seen in Peru in the 1990s and Haiti in 2010," first author Matthew Dorman from the Wellcome Sanger Institute said in a statement. "If we are to control cholera epidemics efficiently, it is vital that we are able to distinguish and understand the differences between the local, endemic V. cholerae that coexist alongside 7PET during a cholera epidemic."

He and his colleagues sequenced 490 clinical and environmental V. choleraeisolates collected in Argentina between 1992 and 2002. Most, or 86.7 percent, of the isolates belong to the 7PET phylogenetic lineage, and of those, 99 percent belong to the LAT-1 sub-lineage that was introduced into neighboring Peru in 1991.

Overall, the LAT-1 genomes were highly similar, the researchers found. They estimated that 0.03 percent of the reference LAT-1 genome, isolated from a Peruvian traveler in 1992, had undergone recombination. In addition, of the 2,600 SNVs they uncovered, 72.6 percent were only found in one isolate. 

These findings suggested that the Argentinian outbreak could be traced to one highly clonal sub-lineage of 7PET that likely arrived from Peru.

Cholera samples are also characterized by their serotype, and this outbreak was characterized by shifts between the Inaba and Ogawa serotypes. The Ogawa serotype is due to the methylation of a sugar on the O1 lipopolysaccharide chain by the WbeT enzyme, while a lack of such methylation leads to an Inaba serotype. 

By analyzing their wbeT genes, the researchers uncovered a number of protein-disrupting mutations, and they further compared their LAT-1 samples to Inaba isolates from West Africa that shared a common ancestor. The isolates harbored different wbeT-disrupting mutations, suggesting the alterations arose independently in different parts of the world.

Through their phylogenetic analysis, the researchers additionally found the Ogawa V. cholerae serotypes from Argentina were closely related to Inaba isolates from Peru.

At the same time, the researchers analyzed non-7PET V. cholerae isolates. These samples, they noted, were much more diverse and had more greatly expanded accessory genomes than the epidemic samples.

While endemic V. cholerae can lead to disease, it doesn't raise the same risk as epidemic strains. Because of this, the researchers noted, it is important to study the diversity of endemic strains, as this can influence public health surveillance approaches.

"This gave us a unique opportunity to understand the detailed evolution of V. cholerae bacteria in our country," Josefina Campos, senior author from INEI-ANLIS "Dr. Carlos G. Malbrán," said in a statement. "We will be able to use these data and this experience to inform how we monitor and respond to any future cholera outbreaks – bacteria that cause epidemics pose a very different risk to those that do not; this is simple information that is critical for disease control."