The incidence of antibiotic resistance is increasing in many groups of disease-causing bacteria. Although some bacteria become resistant to antibiotics through mutation, acquisition of antibiotic resistance genes from other bacteria is probably more common. This proposal focuses on the genus Bacteroides. Bacteroides species are among the numerically predominant species of bacteria in the human colon. Bacteroides species are also opportunistic pathogens that can cause life-threatening infections. Many Bacteroides strains have become resistant to multiple antibiotics. Transfer of resistance genes among these strains appears to have occurred mainly through the actions of a group of conjugative transposons (CTns), represented by CTnDOT. CTnDOT excises from the chromosome to form a circular intermediate, which transfers by conjugation to a recipient and integrates into the recipient's chromosome. During the previous funding period, genes responsible for excision and transfer were identified and shown to be controlled by a complex set of regulatory genes. These genes may allow the CTn to coordinate excision and transfer so that nicking to initiate transfer of the circular form does not occur until excision is complete. Both excision and transfer are stimulated over 1,000-fold by the antibiotic tetracycline. Previously, we found that three genes, rteA, rteB and rteC function as central regulatory genes. We propose that RteC triggers expression of two excision genes, excA and excB. The first specific aim of the proposal is to test this hypothesis.
The second aim i s to determine how ExcA and ExcB, presumably in concert with the CTn integrase (Int), catalyze excision and circularization of the CTn. The third specific aim is to determine whether RteC also controls expression of a gene currently designated as orf5 and to test the hypothesis that Orf5 in turn controls the expression of transfer (tra) genes. The fourth specific aim is to answer the question of how effective coordination of excision and transfer actually is. The last aim is to define the characteristics and functions of RteA and RteB, which control expression of rteC.

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Research Project (R01)
Project #
2R01AI022383-14A2
Application #
6370460
Study Section
Special Emphasis Panel (ZRG1-MBC-1 (01))
Program Officer
Rhoades, Marcus M
Project Start
1985-09-30
Project End
2006-05-31
Budget Start
2001-07-01
Budget End
2002-05-31
Support Year
14
Fiscal Year
2001
Total Cost
$260,662
Indirect Cost
Name
University of Illinois Urbana-Champaign
Department
Microbiology/Immun/Virology
Type
Schools of Arts and Sciences
DUNS #
041544081
City
Champaign
State
IL
Country
United States
Zip Code
61820
Hopp, Crystal M; Gardner, Jeffrey F; Salyers, Abigail A (2015) The Xis2d protein of CTnDOT binds to the intergenic region between the mob and tra operons. Plasmid 81:63-71
Keeton, Carolyn M; Park, Jiyeon; Wang, Gui-Rong et al. (2013) The excision proteins of CTnDOT positively regulate the transfer operon. Plasmid 69:172-9
Waters, Jillian L; Wang, Gui-Rong; Salyers, Abigail A (2013) Tetracycline-related transcriptional regulation of the CTnDOT mobilization region. J Bacteriol 195:5431-8
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Park, Jiyeon; Salyers, Abigail A (2011) Characterization of the Bacteroides CTnDOT regulatory protein RteC. J Bacteriol 193:91-7
Wang, Gui-Rong; Shoemaker, Nadja B; Jeters, Robert T et al. (2011) CTn12256, a chimeric Bacteroides conjugative transposon that consists of two independently active mobile elements. Plasmid 66:93-105
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Song, Bo; Wang, Gui-Rong; Shoemaker, Nadja B et al. (2009) An unexpected effect of tetracycline concentration: growth phase-associated excision of the Bacteroides mobilizable transposon NBU1. J Bacteriol 191:1078-82
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Jeters, Robert T; Wang, Gui-Rong; Moon, Kyung et al. (2009) Tetracycline-associated transcriptional regulation of transfer genes of the Bacteroides conjugative transposon CTnDOT. J Bacteriol 191:6374-82

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