The goal of this application is to identify plasmid DNA partitioning systems that are active during both vegetative growth and sporulation in two different species of Bacillus. New tools for elucidating the mechanisms underlying plasmid segregation will be developed using the model organism B. subtilis, and then applied to B. megaterium. Utilizing two different Bacillus strains to study this problem will allow us to take advantage of the unique strengths that each organism and its indigenous plasmids offer, while maintaining a focused goal of understanding how conserved elements of the microbial DNA segregation machinery functions during sporulation to ensure that every spore inherits at least one copy of the plasmid. Plasmid segregation during sporulation provides an attractive system for studying DNA segregation because: 1) both the plasmids and the sporulation process are not nonessential; 2) the nearly 10 fold smaller volume of the forespore compared to the mothercell demands an efficient plasmid partitioning system; 3) cell-specific transcription factors become active during sporulation, allowing the development of powerful genetic and cell biology assays for DNA segregation during sporulation; and 4) many Bacillus plasmids do not encode proteins related to either the ParA or ParM families of plasmid segregation proteins, suggesting that novel partitioning mechanisms are at work. Since a wide variety of virulence factors are encoded on plasmids in pathogenic strains of Bacillus, understanding how plasmids are transmitted from one generation to the next is important for understanding the evolution and spread these key virulence determinants. These studies will allow the development of better genetic tools and plasmid vectors useful for manipulating many Bacillus species. ? ? ?

Agency
National Institute of Health (NIH)
Institute
National Institute of General Medical Sciences (NIGMS)
Type
Research Project (R01)
Project #
1R01GM073898-01A2
Application #
7147786
Study Section
Prokaryotic Cell and Molecular Biology Study Section (PCMB)
Program Officer
Dearolf, Charles R
Project Start
2006-08-01
Project End
2010-07-31
Budget Start
2006-08-01
Budget End
2007-07-31
Support Year
1
Fiscal Year
2006
Total Cost
$288,424
Indirect Cost
Name
University of California San Diego
Department
Biology
Type
Schools of Arts and Sciences
DUNS #
804355790
City
La Jolla
State
CA
Country
United States
Zip Code
92093
Parent, Kristin N; Erb, Marcella L; Cardone, Giovanni et al. (2014) OmpA and OmpC are critical host factors for bacteriophage Sf6 entry in Shigella. Mol Microbiol 92:47-60
Erb, Marcella L; Kraemer, James A; Coker, Joanna K C et al. (2014) A bacteriophage tubulin harnesses dynamic instability to center DNA in infected cells. Elife 3:
Sakoulas, George; Rose, Warren; Nonejuie, Poochit et al. (2014) Ceftaroline restores daptomycin activity against daptomycin-nonsusceptible vancomycin-resistant Enterococcus faecium. Antimicrob Agents Chemother 58:1494-500
Sakoulas, George; Okumura, Cheryl Y; Thienphrapa, Wdee et al. (2014) Nafcillin enhances innate immune-mediated killing of methicillin-resistant Staphylococcus aureus. J Mol Med (Berl) 92:139-49
Zehr, Elena A; Kraemer, James A; Erb, Marcella L et al. (2014) The structure and assembly mechanism of a novel three-stranded tubulin filament that centers phage DNA. Structure 22:539-48
Barr, Jeremy J; Auro, Rita; Furlan, Mike et al. (2013) Bacteriophage adhering to mucus provide a non-host-derived immunity. Proc Natl Acad Sci U S A 110:10771-6
Werth, B J; Vidaillac, C; Murray, K P et al. (2013) Novel combinations of vancomycin plus ceftaroline or oxacillin against methicillin-resistant vancomycin-intermediate Staphylococcus aureus (VISA) and heterogeneous VISA. Antimicrob Agents Chemother 57:2376-9
Nonejuie, Poochit; Burkart, Michael; Pogliano, Kit et al. (2013) Bacterial cytological profiling rapidly identifies the cellular pathways targeted by antibacterial molecules. Proc Natl Acad Sci U S A 110:16169-74
Sakoulas, George; Bayer, Arnold S; Pogliano, Joseph et al. (2012) Ampicillin enhances daptomycin- and cationic host defense peptide-mediated killing of ampicillin- and vancomycin-resistant Enterococcus faecium. Antimicrob Agents Chemother 56:838-44
Kraemer, James A; Erb, Marcella L; Waddling, Christopher A et al. (2012) A phage tubulin assembles dynamic filaments by an atypical mechanism to center viral DNA within the host cell. Cell 149:1488-99

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