France Daigle of the University of Montreal in Canada will identify the microorganisms that enable the survival of the typhoid fever-causing bacterium, Salmonella enterica serovar Typhi, at low levels in water, and thereby enhances disease spread. Typhoid fever spreads through contaminated food and water, and results in over 125,000 deaths annually worldwide. S. Typhi are so-called auxotrophic bacteria because they rely on an external source of the essential amino acids that they need to grow. Microbial interactions may provide nutrients and also increase bacterial fitness and support persistence by protecting them from the environment, thereby increasing the rate of disease transmission. They will assemble a microbial community in water consisting of three components: one protozoan (from a group known to promote bacterial survival); a defined consortium of bacteria representative of the human fecal microbiota; and fluorescently-tagged S. Typhi. They will evaluate the ability of S. Typhi to grow in these microcosms, and how they grow, such as in biofilms or inside the protozoa. They will also determine whether these persistent S. Typhi are better able to infect and survive in human cells. Finally, water samples from an endemic region in East Africa will be analyzed for the presence of S. Typhi and identified beneficial microbial partners using quantitative PCR.

Windy Tanner and Jim VanDerslice of the University of Utah in the U.S., together with colleagues from Mehran University of Engineering and Technology in Pakistan, will analyze water samples to determine the conditions that promote the survival of the typhoid fever causing bacterium Salmonella Typhi, and they will use metagenomic deconvolution to identify any gene exchange from other microbial species that may produce drug-resistant strains. S. Typhi is responsible for over 100,000 deaths each year, mostly in the developing world where fecal contamination of food and drinking water is common. The emergence of drug-resistant strains has limited the available treatment options. Biofilms are environmental niches with complex microbial communities and are ubiquitous in the environments where S. Typhi is commonly found. They will sample water and biofilms from a variety of these environments along the fecal-drinking water transmission route in the Sindh province of Pakistan and test for the presence of S. Typhi using qPCR and culture methods. They will also evaluate whether specific organisms stabilize and protect S. Typhi in these biofilms and could cause resistance gene exchange.

Ahmad Khalil of Boston University in the U.S. will develop a low-cost bioreactor platform to simultaneously optimize growth conditions of multiple bacterial species for large scale production of biotherapeutics. The human gut microbiome plays an essential role in health and development and living microbial biotherapeutics could be an effective treatment in the case of damage by illness or malnutrition. Commercial production is limited by the capacity of bioreactors, which are costly and challenging to scale and relatively inflexible. Using their eVOLVER continuous culture system, which is modular, inexpensive, and highly scalable, they will adapt the set-up and optimize protocols to allow for the management of unique growth conditions for individual species in parallel, and dynamic mixing of cultures from individual pools to precisely tune multi-species formulations. They will conduct full-scale tests to evaluate their approach for optimizing production of human gut microbiota.

To develop new vaccines against some of the world's biggest killers, including HIV, malaria, and tuberculosis, scientists must be able to evaluate promising candidates. Some of the most promising potential vaccines, are made from weakened live versions of the infectious agent. As a result, they cannot be studied in human trials unless researchers can be confident that the weakened vaccines will be safe. Dr. Flavell and his colleagues are working to genetically engineer laboratory mice whose immune systems are similar enough to humans to permit testing of vaccines against diseases that disproportionately affect people in the developing world. Flavell (Grand Challenges in Global Health: 2005-2015 retrospective)