loading
loading
NIH grant 1F31AI191731-01A1: Interactions of A Conserved Regulatory Switch Controls Physiology in Bacilli and Clostridia
Institute: {'code': 'AI', 'abbreviation': 'NIAID', 'name': 'National Institute of Allergy and Infectious Diseases', 'admin_org_id': '12500003', 'admin_funding_url': ''}. PI: Ysabella Victoria Alcaraz. Award: $50114.
Start: 2026-09-30T00:00:00.
PROJECT SUMMARY/ABSTRACT
Pathogenic spore-forming bacteria cause over one million infections, costing billions of dollars in healthcare
costs, and thousands of deaths annually. Sporulating bacteria rely on the transition from a vegetative state to
spore for survival. A dormant bacterial spore can survive unfavorable conditions for millions of years. This is
because spores are extremely resistant to heat, chemicals, and radiation. To prevent spore-related diseases, it
is crucial to uncover how these bacteria decide to initiate sporulation. Yet, there is a gap in knowledge of the
mechanisms behind bacterial sporulation initiation and transmission. Sporulation initiation is activated by the
master transcriptional regulator, Spo0A. Previous data show that Spo0A phosphorylation activates sporulation.
However, Spo0A activation can be blocked, preventing spore formation. Spo0E is a key regulator in all spore
formers that can inhibit sporulation by inactivating Spo0A. In addition, Spo0E was recently found to control
motility, as well as virulence in some species. However, the specific interactions that allow Spo0E to regulate
sporulation, motility, and toxin production in different bacteria remain unclear. The long-term goal of this project
is to identify how Spo0E controls the switch from a motile vegetative cell state to a dormant spore. Based on
prior data, my central hypothesis is that Spo0E evolved to regulate physiology through specific
interactions with the major effectors of virulence, motility, and sporulation in Bacilli and Clostridia. The
specific objectives are to determine the Spo0E regions critical for its physiologic functions and to define Spo0E
interactions with Spo0A and other partner regulators. The hypothesis will be tested through experiments detailed
in two specific aims. In Specific Aim 1, Spo0E amino acid residues of interest will be mutated to investigate their
impact on sporulation and motility/toxin production in Clostridioides difficile and Bacillus subtilis. In Specific Aim
2, Spo0E variants from both species will be tested for their ability to interact with binding partners using molecular
biology and biochemical approaches. These experiments will uncover how Spo0E homologs regulate major
physiological processes in spore-forming Firmicutes. This research is conceptually innovative because it
explores the overlap and divergences in sporulation initiation between B. subtilis and C. difficile. The proposed
research is also significant because it ultimately gives insight to the evolution of critical B. subtilis and C. difficile
regulatory mechanisms. Overall, this research will provide a foundation in understanding targets of sporulation
and motility in sporulating bacteria and an excellent training for my doctoral studies to support my career goals.document fetched 2026-10-24 02:47