Abstract
BackgroundIntegrons are found in hundreds of environmental bacterial species, but are mainly known as the agents responsible for the capture and spread of antibiotic-resistance determinants between Gram-negative pathogens. The SOS response is a regulatory network under control of the repressor protein LexA targeted at addressing DNA damage, thus promoting genetic variation in times of stress. We recently reported a direct link between the SOS response and the expression of integron integrases in Vibrio cholerae and a plasmid-borne class 1 mobile integron. SOS regulation enhances cassette swapping and capture in stressful conditions, while freezing the integron in steady environments. We conducted a systematic study of available integron integrase promoter sequences to analyze the extent of this relationship across the Bacteria domain.ResultsOur results showed that LexA controls the expression of a large fraction of integron integrases by binding to Escherichia coli-like LexA binding sites. In addition, the results provide experimental validation of LexA control of the integrase gene for another Vibrio chromosomal integron and for a multiresistance plasmid harboring two integrons. There was a significant correlation between lack of LexA control and predicted inactivation of integrase genes, even though experimental evidence also indicates that LexA regulation may be lost to enhance expression of integron cassettes.ConclusionsAncestral-state reconstruction on an integron integrase phylogeny led us to conclude that the ancestral integron was already regulated by LexA. The data also indicated that SOS regulation has been actively preserved in mobile integrons and large chromosomal integrons, suggesting that unregulated integrase activity is selected against. Nonetheless, additional adaptations have probably arisen to cope with unregulated integrase activity. Identifying them may be fundamental in deciphering the uneven distribution of integrons in the Bacteria domain.
Highlights
Integrons are found in hundreds of environmental bacterial species, but are mainly known as the agents responsible for the capture and spread of antibiotic-resistance determinants between Gram-negative pathogens
Despite the importance of integrons in the acquisition and spread of antibiotic-resistance determinants and, from a broader perspective, in bacterial adaptation, little was known about the regulatory control and dynamics of cassette recombination until recently, when we reported that the expression of the integron integrases in the V. cholerae superintegron and in a class 1 mobile integron was controlled by the SOS response [25]
We have shown that expression of V. cholerae and E. coli pAT674 integrase genes is controlled by the SOS response, leading to heightened rates of integrase-mediated recombination upon SOS induction [25]
Summary
Integrons are found in hundreds of environmental bacterial species, but are mainly known as the agents responsible for the capture and spread of antibiotic-resistance determinants between Gram-negative pathogens. First described in the late 1980s in connection with the emergence of antibiotic resistance [1], integrons always contain three functional components: an are typically associated with transposons and conjugative plasmids, ensuring their dissemination across bacterial species They are present mostly in the Proteobacteria, but have been reported in other bacterial phyla, such as Gram-positive bacteria [9]. Despite the importance of integrons in the acquisition and spread of antibiotic-resistance determinants and, from a broader perspective, in bacterial adaptation, little was known about the regulatory control and dynamics of cassette recombination until recently, when we reported that the expression of the integron integrases in the V. cholerae superintegron and in a class 1 mobile integron was controlled by the SOS response [25]
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