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Cholera Strain Behind Epidemic in Yemen Sequenced

NEW YORK (GenomeWeb) – The bacteria behind the cholera outbreak in Yemen stems from a sublineage that originated in South Asia and later caused outbreaks in East Africa before its introduction to Yemen.

The first cases in the cholera epidemic in Yemen, which is in the grip of a civil war, were reported in September 2016 and since then there have been more than 1.1 million cases and 2,300 deaths reported.

Pasteur Institute-led researchers sequenced 42 Vibrio cholerae isolates obtained from various parts of Yemen throughout the epidemic for sequencing. As they reported today in Nature, they traced the origin of the bacteria affecting Yemen to a single sublineage of the seventh pandemic V. cholerae O1 El Tor (7PET) lineage. They also noted that this sublineage is susceptible to some antibiotics used to treat cholera, including polymyxin B, unlike other El Tor lineages.

"[A] single recent 7PET sublineage with an unusual antimicrobial resistance phenotype is responsible for the cholera epidemic in Yemen," Pasteur's Marie-Laure Quilici and her colleagues wrote in their paper.

The researchers amassed 39 cholera isolates from patients who lived in three different regions of Yemen and three isolates from patients at a refugee center near the Saudi Arabian border for sequencing analysis. These isolates were collected between early October 2016 and the end of August 2017, encompassing both waves of the epidemic. The researchers also obtained 74 7PET isolates from South Asia, the Middle East, and Central and Eastern Africa for comparison, alongside a collection of more than a thousand global 7PET samples.

Based on nearly 10,000 SNVs, the researchers constructed a maximum likelihood phylogeny of these 1,203 cholera samples. All the Yemeni samples clustered together, indicating both waves of the outbreak were due to a single clone, rather than separate bacterial introductions. These Yemeni samples all belong to a recently emerged 7PET wave 3 clade that harbors the cholera toxin subunit B gene variant ctxB7.

The Yemeni isolates, though, differ from other isolates that have been circulating in the Middle East, the researchers reported. Instead, they found the Yemeni isolates to be more closely related to samples collected from outbreaks in eastern Africa that occurred between 2015 and 2016. Together, those samples formed a new sublineage, called T13.

The researchers further estimated that the most recent common ancestor of the Yemeni samples circulated in January 2016, and that the ctxB7 7PET wave 3 clade first arose in South Asia in the early 2000s before spreading.

According to the researchers, ctxB7 isolates were first detected in Kolkata in 2006 and were later found in outbreaks in West Africa, Haiti, and East Africa before Yemen.

The Yemeni epidemic samples also harbored genetic variants that affect their susceptibility to various antibiotics. For instance, they have a mutation in the DNA gyrase gene gyrA and the topoisomerase IV gene parC that give resistance to nalidixic and decreased susceptibility to ciprofloxacin. Meanwhile, other mutations give it resistance to nitrofurans.

However, unlike most other El Tor specimens, these Yemeni isolates appear susceptible to polymyxin B. Here, 97 percent of polymyxin B-susceptible isolates — which includes all the Yemeni samples — have a non-synonymous SNV in the vprA gene, which, when disrupted is known to restore polymyxin susceptibility.

As this clade contributed to the 2010 Haiti cholera outbreak as well as the epidemic in Yemen, the researchers said it highlights the public health threat cholera poses. "Our study illustrates the key role of genomic microbial surveillance and cross-border collaborations in understanding the global spread of cholera, the evolution of virulence, and determinants of antibiotic resistance," they added.