In January 2010, a catastrophic earthquake hit Haiti, killing more than 200,000 people and displacing over 1 million, according to the Centers for Disease Control and Prevention (CDC), and creating the ideal conditions for the spread of cholera.
Conditions facilitating infection with Vibrio cholerae bacteria, the pathogen responsible for cholera, included contaminated water and food sources, inadequate water treatment and poor sanitation and hygiene. Following the initial identification of cholera in October 2010, the CDC reports that over 470,000 Haitians were diagnosed with the severe diarrheal illness and nearly 7,000 died.
In a recent study published in Infection and Immunity, scientists at Northwestern and the University of California at Santa Cruz discovered that the V. cholerae strain responsible for the 2010 epidemic in Haiti is a hypervirulent variant.
For the past 50 years, the cholera pandemic has stemmed from a strain called El Tor O1, which spread globally in three distinct waves. The wave 3 altered El Tor (AET) V. cholerae line has been the primary cause of human cholera disease since the late 1990s. The emergence of this new strain is linked to a higher incidence of lethal outcomes.
“I became keenly interested in the idea that this new globally circulating strain that was introduced into Haiti might be hypervirulent when we noticed these strains shared an inactivating mutation in a virulence gene that my lab had determined contributed to infection onset,” said study co-principal investigator Karla Satchell, PhD, professor of Microbiology-Immunology. “We hypothesized this mutation could only be tolerated in a bacterium that had other mutations that increased its overall virulence. We set out to understand what other factors may have changed in this strain and why.”
Scientists conducted a phenotypic analysis of the particular wave 3 strain responsible for the Haiti epidemic – AET 2010EL-1786 – and compared it to the wave 1 El Tor strains regularly used in cholera research.
“I did key experiments myself, although I had excellent help from several people,” said Satchell. “When I realized that the hypervirulence might be linked to a signal molecule called cyclic-di-GMP, I was happy to then contact my good friend and colleague Fitnat Yildiz at Santa Cruz, where a post-doc was excited to help out to conduct the appropriate measurements of the signal molecule.”
The investigators discovered that the Haiti isolate 2010EL-1786 bacterial strain has specific indicators of hypervirulence, including:
- Increased production of cholera toxin (CT), the primary disease-causing factor of the cholerae bacterium, and another toxin called hemolysin
- Increased motility
- Increased competitive fitness for colonization
The clinical implications of the hypervirulent strain are significant.
“The increased production of the toxins would create a situation where the bacterium would not only be able to establish itself more readily in the human gut, but also cause a more severe diarrhea,” Satchell explained. “A surprise, though, was that this comes at a cost to bacterial survival in the environment, indicating this strain is more dependent on human-to-human transmission, a situation that can more readily occur when infrastructure for clean water is destroyed.”
In addition, the study’s findings underscore the high capacity of the wave 3 cholera strains to evolve. The phenotypically distinct 2010EL-1786 strain introduced in Haiti is the result of the positive selection of increased virulence through cycles of human transmission.
“I think our study will have long-term impact as researchers tracking epidemics have generally focused on limited information in decisions regarding strategies to control epidemics and our findings suggest that they need to consider that there are hypervirulent strains circulating in the world even today,” said Satchell.
Additional Northwestern study authors include Jennifer Wong, Jessica Queen, and Shivani Agarwal, PhD.
This research was funded by the Northwestern Medicine Catalyst Fund, the National Institutes of Health (NIH) National Institute of Allergy and Infectious Diseases (NIAID) grants R01AI092825, R01AI098369, R01AI102584, and the NIH National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) grant 1F30DK084623.