A Little Bit of Background

Vibrio cholerae is a species of Gram-negative bacteria found worldwide as natural inhabitants of marine ecosystems. Some strains are human pathogens. When pathogenic strains are ingested, usually via contaminated water, bacteria can colonize intestinal tissues and cause the life-threatening diarrheal disease known as cholera.

We often think of cholera as an ancient, epidemic disease, restricted today to impoverished countries with inadequate infrastructure for sanitation. However, sporadic disease occurs across the globe, and cholera is also a re-emerging threat. Reintroduction into Haiti and increased incidence due to natural disasters, refugee situations, and global warming, have brought cholera to the forefront of public attention. The morbidity and mortality caused by cholera, especially in endemic parts of our world, places a large burden on global society and contributes to modern day economic and humanitarian challenges caused by infectious disease.

As a species, V. cholerae encompasses a wide diversity of strains that can be classified based on serogroup. Epidemic cholera is caused only by O1 or O139 serogroup strains, which are largely clonal and exclusively use well characterized virulence factors to colonize the small intestine (toxin co-regulated pilus, TCP) and cause secretory diarrhea (cholera toxin, CT). However, strains of other serogroups, collectively called non-O1/non-O139 serogroup strains, are mainly responsible for worldwide sporadic disease and interepidemic disease in endemic areas. Unlike O1 and O139 serogroup strains, non-O1/non-O139 serogroup strains can be highly variable in genetic content. Multiple mechanisms of horizontal gene transfer facilitate diversity and evolution, and have resulted in strains that can cause disease using TCP/CT-independent mechanisms. In fact, most pathogenic non-O1/non-O139 serogroup strains do not encode TCP or CT, and are largely uncharacterized. Our overarching goal is to discover and characterize the molecular mechanisms used by non-O1/non-O139 sergroup strains to cause disease in a TCP/CT independent manner.