The Vibrio cholerae colonization factor GbpA possesses a modular structure that governs binding to different host surfaces

Vibrio cholerae is a bacterial pathogen that colonizes the chitinous exoskeleton of zooplankton as well as the human gastrointestinal tract. Colonization of these different niches involves an N-acetylglucosamine binding protein (GbpA) that has been reported to mediate bacterial attachment to both marine chitin and mammalian intestinal mucin through an unknown molecular mechanism. We report structural studies that reveal that GbpA possesses an unusual, elongated, four-domain structure, with domains 1 and 4 showing structural homology to chitin binding domains. A glycan screen revealed that GbpA binds to GlcNAc oligosaccharides. Structure-guided GbpA truncation mutants show that domains 1 and 4 of GbpA interact with chitin in vitro, whereas in vivo complementation studies reveal that domain 1 is also crucial for mucin binding and intestinal colonization. Bacterial binding studies show that domains 2 and 3 bind to the V. cholerae surface. Finally, mouse virulence assays show that only the first three domains of GbpA are required for colonization. These results explain how GbpA provides structural/functional modular interactions between V. cholerae, intestinal epithelium and chitinous exoskeletons

Cholera in Oceania

For approximately 200 years, cholera has been feared globally as a disease that can cause rapid-onset epidemics. The causative organisms, Vibrio cholerae O1 and O139 serogroups, are endemic to Southern Asia, but appear to spread globally in waves resulting in seven recognised pandemics to date. The current seventh pandemic has seen the introduction of V. cholerae O1 El Tor into the Oceania region. Since 1962 there have been five large outbreaks at a frequency of approximately one per decade. There have also been regular small outbreaks and clusters of disease throughout the region during the seventh pandemic. The most recent outbreak of cholera in the region occurred in Papua New Guinea in 2009–2011, and this was the largest outbreak to occur in the region to date. In Oceania the majority of people live in high-income settings (Australia and New Zealand) so the risk of cholera transmission is low. Despite this, an estimated 6.5 million people living in the region are at risk of cholera. The most important risk factors are inadequate access to safe water and lack of appropriate sanitation and hygiene measures. However, many other factors may contribute to cholera transmission risk, and people living in Pacific Island countries may be at increased risk in the future due to climate change. Strengthening health delivery services in the region will ensure countries are better equipped to handle future cholera outbreaks; and further understanding the epidemiology of cholera and the causative agent in the region could help prevent future transmission