A Complex Genetic Switch Involving Overlapping Divergent Promoters and DNA Looping Regulates Expression of Conjugation Genes of a Gram-positive Plasmid


Plasmids are extrachromosomal, autonomously replicating units that are harbored by many bacteria. Many plasmids encode transfer function allowing them to be transferred into plasmid-free bacteria by a process named conjugation. Since many of them also carry antibiotic resistance genes, plasmid-mediated conjugation is a major mechanism in the dissemination of antibiotic resistance. In depth knowledge on the regulation of conjugation genes is a prerequisite to design measures interfering with the spread of antibiotic resistance. pLS20 is a conjugative plasmid of the soil bacterium Bacillus subtilis, which is also a gut commensal in animals and humans. Here we describe in detail the molecular mechanism by which the key transcriptional regulator tightly represses the conjugation genes during conditions unfavorable to conjugation without compromising the ability to switch on accurately the conjugation genes when appropriate. We found that conjugation is subject to the control of a unique genetic switch where at least three levels of regulation are integrated. The first level involves overlapping divergent promoters of different strengths. The second layer involves a triple function of the transcriptional regulator. And the third level of regulation concerns formation of a DNA loop mediated by the transcriptional regulator.


Vyšlo v časopise: A Complex Genetic Switch Involving Overlapping Divergent Promoters and DNA Looping Regulates Expression of Conjugation Genes of a Gram-positive Plasmid. PLoS Genet 10(10): e32767. doi:10.1371/journal.pgen.1004733
Kategorie: Research Article
prolekare.web.journal.doi_sk: 10.1371/journal.pgen.1004733

Souhrn

Plasmids are extrachromosomal, autonomously replicating units that are harbored by many bacteria. Many plasmids encode transfer function allowing them to be transferred into plasmid-free bacteria by a process named conjugation. Since many of them also carry antibiotic resistance genes, plasmid-mediated conjugation is a major mechanism in the dissemination of antibiotic resistance. In depth knowledge on the regulation of conjugation genes is a prerequisite to design measures interfering with the spread of antibiotic resistance. pLS20 is a conjugative plasmid of the soil bacterium Bacillus subtilis, which is also a gut commensal in animals and humans. Here we describe in detail the molecular mechanism by which the key transcriptional regulator tightly represses the conjugation genes during conditions unfavorable to conjugation without compromising the ability to switch on accurately the conjugation genes when appropriate. We found that conjugation is subject to the control of a unique genetic switch where at least three levels of regulation are integrated. The first level involves overlapping divergent promoters of different strengths. The second layer involves a triple function of the transcriptional regulator. And the third level of regulation concerns formation of a DNA loop mediated by the transcriptional regulator.


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