This proposal focuses on how spores are formed by Bacillus subtilis. B. subtilis has become a paradigm for the study of spore formation, and of cell differentiation in prokaryotes, because of the ease of its genetic manipulation. All the key regulators of B. subtilis spore formation are also found in other spore forming species including the pathogens B. anthracis, Clostridium tetani, C. perfringens, C. botulinum and C. difficile, the causes of anthrax, tetanus, gas gangrene, botulism and colitis following antibiotic therapy, respectively. The highly resistant spores are critical to the survival of theses species in nature. Conclusions from a study of B. subtilis will have general validity for these species. Spore formation involves a characteristic division into two different cell types, the mother cell and the prespore. The prespore is engulfed by the mother cell and develops into the mature spore. Spore formation requires the action of four RNA polymerase factors, ?F and then ?G in the prespore and ?E and then ?K in the mother cell. It presents a fundamental problem of developmental biology: how is gene expression coordinated with morphological change? The proposal addresses this problem. When the ?F-directed signal from the prespore to activate ?E in the mother cell is delayed, a novel developmental path is taken, in which two spores are formed within one mother cell. This behavior opens up the proposed study of how chromosome replication and growth are controlled during sporulation. It facilitates a study of how genetically identical organisms in the same population can follow different developmental paths. Translocation of the chromosome into the prespore follows activation of ?F. It is proposed to study how completion of translocation leads to engulfment of the prespore by the mother cell and activation of ?G in the engulfed prespore.

Public Health Relevance

This proposal focuses on the fundamental problem of how gene expression is coordinated with morphological changes during formation of spores by Bacillus subtilis. All the key sporulation regulatory genes are also found in related pathogens, including B. anthracis, Clostridium tetani, C. perfringens, C. botulinum and C. difficile. Emphasis is placed on how altering the timing of signaling can change the developmental path taken.

National Institute of Health (NIH)
National Institute of General Medical Sciences (NIGMS)
Research Project (R01)
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Prokaryotic Cell and Molecular Biology Study Section (PCMB)
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Gaillard, Shawn R
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Temple University
Schools of Medicine
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Regan, Genevieve; Itaya, Mitsuhiro; Piggot, Patrick J (2012) Coupling of ýýG activation to completion of engulfment during sporulation of Bacillus subtilis survives large perturbations to DNA translocation and replication. J Bacteriol 194:6264-71
Xenopoulos, Panagiotis; Piggot, Patrick J (2011) Regulation of growth of the mother cell and chromosome replication during sporulation of Bacillus subtilis. J Bacteriol 193:3117-26
Chary, Vasant K; Xenopoulos, Panagiotis; Eldar, Avigdor et al. (2010) Loss of compartmentalization of ?(E) activity need not prevent formation of spores by Bacillus subtilis. J Bacteriol 192:5616-24
Eldar, Avigdor; Chary, Vasant K; Xenopoulos, Panagiotis et al. (2009) Partial penetrance facilitates developmental evolution in bacteria. Nature 460:510-4
Chary, Vasant K; Xenopoulos, Panagiotis; Piggot, Patrick J (2006) Blocking chromosome translocation during sporulation of Bacillus subtilis can result in prespore-specific activation of sigmaG that is independent of sigmaE and of engulfment. J Bacteriol 188:7267-73
Chary, V K; Hilbert, D W; Higgins, M L et al. (2000) The putative DNA translocase SpoIIIE is required for sporulation of the symmetrically dividing coccal species Sporosarcina ureae. Mol Microbiol 35:612-22
Schuch, R; Piggot, P J (1994) The dacF-spoIIA operon of Bacillus subtilis, encoding sigma F, is autoregulated. J Bacteriol 176:4104-10
Bylund, J E; Zhang, L; Haines, M A et al. (1994) Analysis by fluorescence microscopy of the development of compartment-specific gene expression during sporulation of Bacillus subtilis. J Bacteriol 176:2898-905
Birkey, S M; Sun, G; Piggot, P J et al. (1994) A pho regulon promoter induced under sporulation conditions. Gene 147:95-100
Moldover, B; Cao, L; Piggot, P J (1994) Identification of a control region for expression of the forespore-specific Bacillus subtilis locus spoVA. Microbiology 140 ( Pt 9):2299-304

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