How is the process of development controlled? What is the circuitry involved in the cell's decision to simply divide or to begin the process of differentiation? We have isolated and characterized several Bacillus subtilis genes which are involved in the transition from vegetative growth to the developmental mode which results in the appearance of dormant endospores. These genes show complex patterns of regulation, both at the level of transcription (alternative RNA polymerases) and translation, and one of the aims of the proposal is to study the nature of the regulatory mechanisms, i.e., promoter structure, cis and trans- acting factors involved in gene activation, in vitro transcription, etc. We postulate that many of the proteins encoded by early sporulation genes, of the spoO class, encode proteins which function during vegetative growth as well as at the beginning of the differentiation process, and that these proteins form a functional complex at some point during the growth cycle. Homology between two of the early spoO proteins, spoOA and spoOF, and a series of regulatory proteins involved in the sensing of environmental signals in other bacteria, suggests model for the control of sporulation. Another of the aims of this proposal is to purify spoO proteins and to provide evidence for the model. One of the genes we have isolated, the sin ORF2 seems to code for a repressor of certain late growth functions, i.e., sporulation and exprotease synthesis, but is a positive regulator for competence genes. Our last aim is to study the sin gene product and its role in the regulation of differentiation.

Agency
National Institute of Health (NIH)
Institute
National Institute of General Medical Sciences (NIGMS)
Type
Research Project (R01)
Project #
5R01GM032651-08
Application #
3281704
Study Section
Microbial Physiology and Genetics Subcommittee 2 (MBC)
Project Start
1983-07-01
Project End
1993-06-30
Budget Start
1990-07-01
Budget End
1991-06-30
Support Year
8
Fiscal Year
1990
Total Cost
Indirect Cost
Name
Public Health Research Institute
Department
Type
DUNS #
City
Newark
State
NY
Country
United States
Zip Code
Shafikhani, Sasha H; Mandic-Mulec, Ines; Strauch, Mark A et al. (2002) Postexponential regulation of sin operon expression in Bacillus subtilis. J Bacteriol 184:564-71
Rodriguez, G M; Gold, B; Gomez, M et al. (1999) Identification and characterization of two divergently transcribed iron regulated genes in Mycobacterium tuberculosis. Tuber Lung Dis 79:287-98
Dussurget, O; Timm, J; Gomez, M et al. (1999) Transcriptional control of the iron-responsive fxbA gene by the mycobacterial regulator IdeR. J Bacteriol 181:3402-8
Lewis, R J; Brannigan, J A; Offen, W A et al. (1998) An evolutionary link between sporulation and prophage induction in the structure of a repressor:anti-repressor complex. J Mol Biol 283:907-12
Dussurget, O; Smith, I (1998) Interdependence of mycobacterial iron regulation, oxidative-stress response and isoniazid resistance. Trends Microbiol 6:354-8
Smith, I; Dussurget, O; Rodriguez, G M et al. (1998) Extra and intracellular expression of Mycobacterium tuberculosis genes. Tuber Lung Dis 79:91-7
Lewis, R J; Brannigan, J A; Smith, I et al. (1996) Crystallisation of the Bacillus subtilis sporulation inhibitor SinR, complexed with its antagonist, SinI. FEBS Lett 378:98-100
Dussurget, O; Rodriguez, M; Smith, I (1996) An ideR mutant of Mycobacterium smegmatis has derepressed siderophore production and an altered oxidative-stress response. Mol Microbiol 22:535-44
Schmitt, M P; Predich, M; Doukhan, L et al. (1995) Characterization of an iron-dependent regulatory protein (IdeR) of Mycobacterium tuberculosis as a functional homolog of the diphtheria toxin repressor (DtxR) from Corynebacterium diphtheriae. Infect Immun 63:4284-9
Mandic-Mulec, I; Doukhan, L; Smith, I (1995) The Bacillus subtilis SinR protein is a repressor of the key sporulation gene spo0A. J Bacteriol 177:4619-27

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