## 2 Transcriptional Regulation in Integrons
### Interplay between Integrase and Gene Cassette Expression in Class 1 Integrons
#### 2.6.1 Integrase Activity Is Linked and Inversely Correlated to Gene Cassette Expression
However, although the presence of an active P2 resulted in LexA binding site disruption, derepressing _intI1_ expression, it does not interfere with P\({}_{\text{intI1}}\) promoter activity, demonstrating that the 3 bp-overlapping between P\({}_{\text{intI1}}\) and P2 -10 hexamers was not sufficient to provoke transcriptional interference. On the other hand, P\({}_{\text{intI1}}\) had no impact on gene cassette expression driven by Pc variants or P2, which is in agreement with the fact that Pc is not regulated by SOS response. However, in a class 1 integron carrying PcS, gene cassette and _intI1_ transcription is coupled due to the negative interference of PcS on \(\mathrm{P_{intI1}}\) activity by transcription interference. Additionally, transcription interference evoked by PcS and \(\mathrm{P_{intI1}}\) activity proved to be an important mechanism of integration regulation in _A. baumannii_. As mentioned in the previous topic, _A. baumantii_ lacks the LexA repressor, allowing constitutive integrase expression in this species. In this case, the transcriptional interference mediated by PcS led to a decrease in integrase expression, counterbalancing the lack of LexA-driven integrase repression. This modulation avoided the deleterious effects of unregulated integrase, explaining the remarkable predominance of PcS in class 1 integrins from _A. baumannii_[43]. Therefore, besides Pc and P2 promoters play a relevant role in gene cassette transcription, they are also linked with the integron functionality [101]. 6.3 Global Regulators Concomitantly Control the Activity of \(\mathrm{P_{intI1}}\) and Cassette Promoters in Class 1 Integrons  
FIS, IHF, and H-NS are multifunctional proteins that act as recombination accessory elements, nucleoid compaction proteins, and global transcriptional regulators of many distinct metabolic pathways [120]. [PERSON] et al. [20] demonstrated that these global regulators concomitantly interfere with integrase and cassette expression in class 1 integrons, modulating cellular integrase concentrations in response to different host growth phases. The FIS protein repressed both integrase and cassette expression and seemed to stabilize LexA occupancy via their closely adjacent sites in the integron promoter regions, contributing to maximum LexA repressor activity. Conversely, IHF acted as a LexA-independent weak activator of \(\mathrm{P_{intI1}}\) and cassette promoters, while the H-NS protein repressed \(\mathrm{P_{intI1}}\) but activated both Pc and the functional P2 promoters. Therefore, the resistance gene cassette expression regulation was considered so far as only relying on Pc strengths and the cassette position effect. These data altogether revealed a much more complex and fine-tuning intertwined regulation, which lies on the perfect counterbalance between cassette recombination mediated by integrase activity and the expression capacity of Pc promoter [26], and on the direct link to host cell physiology process [17; 18; 19; 21].