Integrative and conjugative elements (ICEs) are chromosomally encoded mobile genetic elements that can transfer DNA between bacterial strains. Recently, as part of efforts to determine hypothetical gene functions, we have discovered an important regulatory module encoded on an ICE known as TnSmu1 on theStreptococcus mutanschromosome. The regulatory module consists of a cI-like repressor with a helix-turn-helix DNA binding domainimmRSmu(immunity repressor) and a metalloproteaseimmASmu(anti-repressor). It is not possible to create an in-frame deletion mutant ofimmRSmuand repression ofimmRSmuwith CRISPRi (CRISPR interference) causes substantial cell defects. We used a bypass of essentiality (BoE) screen to discover genes that allow deletion of the regulatory module. This revealed that conjugation genes, located within TnSmu1, can restore the viability of animmRSmumutant. Deletion ofimmRSmualso leads to production of a circular intermediate form of TnSmu1, which is also inducible by the genotoxic agent mitomycin C. To gain further insights into potential regulation of TnSmu1 by ImmRSmuand broader effects onS. mutansUA159 physiology, we used CRISPRi and RNA-seq. Strongly induced genes included all the TnSmu1 mobile element, genes involved in amino acid metabolism, transport systems and a type I-C CRISPR-Cas system. Lastly, bioinformatic analysis shows that the TnSmu1 mobile element and its associated genes are well distributed acrossS. mutansisolates. Taken together, our results show that activation of TnSmu1 is controlled by theimmRASmumodule, and that activation is deleterious toS. mutans, highlighting the complex interplay between mobile elements and their host.