Genetic tracking and characterization of naturally occurring Vibrio cholerae causing endemic cholera in Bangladesh

Burden

Cholera, a scourge, remains one of the major causes of morbidity and mortality world-wide. The global burden of cholera is estimated to be about 3-5 million cases each year with an estimated deaths of 100,000 to 120,000, majority occurring in the developing countries of Asia and Africa. The causative agent of cholera, Vibrio cholerae, is a genetically versatile bacterial species for which more than 200 serogroups have been identified and for which significant lateral transfer of genes has been demonstrated. Pandemic cholera is generally caused by toxigenic strains of V. cholerae serogroups O1 and O139. V. cholerae O1 has been divided into two biotypes, classical (CL) and El Tor (ET), differing primarily in phenotypic traits and distinct signature genome sequences. Of seven cholera pandemics recorded since 1817, the sixth and presumably the earlier pandemics have been caused by CL biotype, which was replaced in the 1980s by ET biotype initiating the currently ongoing seventh cholera pandemic. The Ganges Delta of the Bay of Bengal has been the traditional home where cholera is endemic for centuries. Although V. cholerae has been an integral part of the bacterial community sharing niche in the estuarine ecosystem of Bay of Bengal, little is known about the aquatic life cycle of V. cholerae, particularly how a pandemic pathogen emerges from the naturally occurring benign population residing this historic ecosystem.

Knowledge gap

Despite intensive research efforts have been made to understand the epidemiology and ecology of V. cholerae, of its physiology and mode of infection in laboratory and in animal model systems, our knowledge is very limited and we still do not fully understand the molecular basis of pathogenicity of the bacterium and why cholera is a seasonal disease, and how a pandemic pathogen takes shape from among the diverse population occurring in the historical niche of the Bay of Bengal estuaries and spread.

Hypothesis

Since cholera has been endemic in the coastal villages of Bay of Bengal (Bangladesh), we hypothesize that the toxigenic V. cholerae responsible for the century-old Asiatic cholera is an integral part of the estuarine vibrio community that are influenced by the local climate, and includes ecological types (ecotypes) unique for this ecosystem.

Objectives

Our primary aim is to:

• Study the population structure (ecotypes) of V. cholerae occurring in the estuarine aquatic ecosystems of the Bay of Bengal

Our secondary aim is to:

• Understand how the naturally occurring toxigenic V. cholerae population (ecotypes) responds to the seasonal change in the regional climate to initiate seasonal cholera.
• Determine virulence potential of epidemiologically significant V. cholerae and related enteric pathogens of environmental and clinical origin by molecular and animal model assays.
• Decipher the transmission of epidemiologically significant V. cholerae regionally, and beyond. For this, we will compare the population structure, virulence and related molecular traits of V. cholerae occurring in the Bay of Bengal estuaries with that of the US east coast (Chesapeake Bay and Falmouth MA), for example.
• Determine antimicrobial resistance (AMR) of environmental and clinical strains of V. cholerae and related enteric pathogens.

Methodologies

V. cholerae (n=2100) would be isolated by culture method from water samples collected monthly from 8 selected Bay of Bengal estuarine pond and river sites located at the cholera-endemic coastal villages of Potuakhali, Bangladesh. Water samples would be collected aseptically in sterile Nalgene bottle and transferred to icddr,b Dhaka hospital for microbiological analysis. “

We designed this study to monitor and characterizing naturally occurring V. cholerae initiating seasonal (endemic) cholerea in Bangladesh.

Genetic tracking of Vibrio cholerae in its natural aquatic environments to provide insights that will aid prediction and preventive measures against upcoming cholera in Bangladesh