The goal of this proposal is to identify the mechanisms of DNA segregation for large, low copy number plasmids in Bacillus species. From studying plasmid pBtoxis in Bacillus thuringiensis, we identified a novel segregation protein belonging to the tubulin superfamily. TubZ is a divergent tubulin like protein that assembles dynamic polymers essential for the stable inheritance of plasmid pBtoxis. Tubulin-like proteins are commonly found on Bacillus virulence plasmids, but how they contribute to plasmid stability is unknown. We have also identified several families of divergent actin-like proteins involved in plasmid DNA segregation in Bacillus subtilis. AlfA of plasmid pLS32 and Alp7A both assemble polymers, but they appear to segregate plasmids by different mechanisms. The goal of this proposal is to understand the biochemical properties, in vivo assembly dynamics, and the functions of Bacillus tubulins and actins involved in plasmid DNA segregation. Since a wide variety of virulence factors are encoded on plasmids in pathogenic strains of Bacillus, such as pXO1 of B. anthracis, understanding how plasmids are transmitted from one generation to the next is important for understanding the evolution and spread of these key virulence determinants.

Public Health Relevance

This study focuses on understanding how bacterial plasmids are inherited. Plasmids play key roles in bacterial pathogenesis, as they are often transmissible and encode antibiotic resistance and virulence traits, such as toxins and capsules. These studies could therefore help identify targets for new narrow spectrum antibiotics, since blocking plasmid stability will in certain infections decrease pathogenicity.

Agency
National Institute of Health (NIH)
Institute
National Institute of General Medical Sciences (NIGMS)
Type
Research Project (R01)
Project #
5R01GM073898-08
Application #
8510655
Study Section
Special Emphasis Panel (ZRG1-GGG-F (02))
Program Officer
Deatherage, James F
Project Start
2006-08-01
Project End
2014-07-31
Budget Start
2013-08-01
Budget End
2014-07-31
Support Year
8
Fiscal Year
2013
Total Cost
$310,173
Indirect Cost
$104,773
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
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