Grant: Discovery Grants Program - Individual

Humans and animals are colonized by trillions of microorganisms that live on every surface of the body. The microbes that inhabit the microbiome play a critical role in the health of their host. Significant progress has been made in recent years in cataloging microbial diversity in microbiomes based on DNA sequence information and our research group has developed novel methods for high resolution profiling of microbial communities that allow discrimination of very closely related species. We use the sequences of universally conserved chaperonin genes as barcodes for discriminating species and identifying functionally related subspecies groups. Chaperonin sequences have more resolving power than other available universal targets and make it possible to use a single gene sequence to discriminate phenotypically distinct groups of bacteria within traditionally defined species. We have applied these methods to discover that a common bacterium in the human vaginal microbiome, Gardnerella vaginalis , is actually made up of four discrete subgroups with distinct properties. Overgrowth of Gardnerella is key to the definition of a common condition called bacterial vaginosis, which is associated with vaginal symptoms and leads to negative reproductive health outcomes including increased susceptibility to sexually transmitted infections and preterm birth. Our discovery of distinct subgroups within Gardnerella may explain the observation that Gardnerella is found in women with vaginosis but also in healthy women, since some subgroups are more likely to cause disease than others. Complicating the story further is that Gardnerella almost always occurs as a mixture of subgroups, with one being far more abundant than the others. We need to understand how the different Gardnerella subgroups compete or cooperate with each other, how they compete for nutrients with other bacteria, and how well each of the subgroups resists the acidic conditions of the healthy vagina to persist and sometimes overgrow and dominate the microbiome. The work we are planning will present opportunities for students to develop skills in conventional microbiology as well as state-of-the-art sequencing, genomics and bioinformatics. Understanding how Gardnerella subgroups differ in their potential to contribute to a disturbed vaginal microbiome and identifying the factors that determine their relative abundance has important implications for the development of improved diagnostic methods, and realization of the potential of using sequence data for identifying high risk microbiomes. The discoveries we make will also contribute to our general understanding of how and why microbiomes change and how we might learn to manipulate those processes to improve human, animal and environmental health, and to advance biotechnology.