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The principal route for dissemination of antibiotic resistance genes is conjugation, by which a conjugative DNA element is transferred from a donor to a recipient cell. Conjugative elements contain genes that are important for their establishment in the new host, for instance by counteracting the host defense mechanisms acting against incoming foreign DNA. Little is known about these establishment genes and how they are regulated.  Here, we deciphered the regulation mechanism of possible establishment genes of plasmid p576 from the Gram-positive bacterium Bacillus pumilus. The dynamics of this system is characterized by a transient pulse of gene expression that defines the narrow window of time during which establishment genes are expressed. Feed-forward motifs and other more complicated regulatory modules are known to be able to produce pulses. We find that a simpler mechanism is possible: a negative feedback loop repressing downstream targets. The key to be able to model this is explicitly considering mRNA expression, that introduces the delay necessary to allow initial expression before eventually repressing it. We find the conditions on cooperativity and different strength of repressions necessary to produce an effective pulse of expression. For establishment genes of conjugative plasmids, this constitutes a novel regulatory mechanism, and more generically, it constitutes a minimal motif for tight regulation of pulses of gene expression.
Reference: Val-Calvo et al., Novel regulatory mechanism of establishment genes of conjugative plasmids, Nucleic Acids Research 46, 11910-11926 (2018)