This application proposes three major areas of work on aspects of spore formation, dormancy, resistance and germination with the bacterium Bacillus subtilis. These areas are: 1) determine the structure and function of the complex between alpha/beta-type small, acid-soluble spore proteins (SASP) and DNA; 2) determine the structure, mechanism and function of the protease (GPR) that degrades SASP during spore germination; and 3) investigate various aspects of spore germination.
Specific aims i nclude: a) determine the structure of SASP-DNA complexes by X-ray crystallography and use these data as well analysis of SASP with further site directed changes to determine the mechanism whereby SASP provide DNA protection; b) mutagenise the GPR coding gene to obtain variants that have lost catalytic activity but retain structure; c) determine the structure of both the active and zymogen forms of GPR; d) examine the role of another possible SASP-specific protease encoded by the yyaC gene; e) determine the mechanism of regulation of the gerK operon that encodes one of the spore's nutrient germinant (Ger) receptors essential for spore germination with nutrients; f) measure the relative level of expression of the three operons (gerA, gerB and gerK) that encode the spore's Ger receptors; g) elucidate the requirement for lipid addition to the proteins encoded by the C-cistrons of the operons that encode the Ger receptors; h) examine the function of the SpoVA proteins in movement of dipicolinic acid (DPA) and/or ions in spore germination; i) determine the location of the SpoVA proteins in spores; j) assess the interaction of various proteins that make up Ger receptors as well as different the Ger receptors themselves; k) determine the factors that affect the spontaneous spore germination that does not require nutrients; I) isolate and characterize mutants that are altered in spontaneous spore germination and mutants whose spores germinate well in the presence of ion channel blockers; and m) express Ger receptors and SpoVA proteins in E. coli to study their function. ? ? ?

National Institute of Health (NIH)
National Institute of General Medical Sciences (NIGMS)
Research Project (R01)
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Microbial Physiology and Genetics Subcommittee 2 (MBC)
Program Officer
Anderson, James J
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University of Connecticut
Schools of Medicine
United States
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Setlow, Peter (2018) Observations on research with spores of Bacillales and Clostridiales species. J Appl Microbiol :
Setlow, Peter; Li, Lei (2015) Photochemistry and Photobiology of the Spore Photoproduct: A 50-Year Journey. Photochem Photobiol 91:1263-90
Plomp, Marco; Carroll, Alicia Monroe; Setlow, Peter et al. (2014) Architecture and assembly of the Bacillus subtilis spore coat. PLoS One 9:e108560
Setlow, Peter (2014) Spore Resistance Properties. Microbiol Spectr 2:
Wei, Jie; Shah, Ishita M; Ghosh, Sonali et al. (2010) Superdormant spores of bacillus species germinate normally with high pressure, peptidoglycan fragments, and bryostatin. J Bacteriol 192:1455-8
Ghosh, S; Setlow, P (2010) The preparation, germination properties and stability of superdormant spores of Bacillus cereus. J Appl Microbiol 108:582-90
Setlow, B; Peng, L; Loshon, C A et al. (2009) Characterization of the germination of Bacillus megaterium spores lacking enzymes that degrade the spore cortex. J Appl Microbiol 107:318-28
Paredes-Sabja, Daniel; Setlow, Peter; Sarker, Mahfuzur R (2009) SleC is essential for cortex peptidoglycan hydrolysis during germination of spores of the pathogenic bacterium Clostridium perfringens. J Bacteriol 191:2711-20
Ghosh, Sonali; Setlow, Peter (2009) Isolation and characterization of superdormant spores of Bacillus species. J Bacteriol 191:1787-97
Ghosh, Sonali; Zhang, Pengfei; Li, Yong-qing et al. (2009) Superdormant spores of Bacillus species have elevated wet-heat resistance and temperature requirements for heat activation. J Bacteriol 191:5584-91

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