Pathogens utilize a diverse set of signal transduction mechanisms to respond to host-derived stresses, with phosphotransfer-mediated two component systems (TCS) playing key roles in virulence factor regulation. Staphylococcus aureus encodes an alternative protease-mediated TCS prototype known as BlaRI involved in inducible β-lactam resistance. BlaR senses extracellular β-lactams, leading to activation of a cytoplasmic protease domain able to cleave DNA-bound BlaI dimers, de-repressing blaRI and blaZ (β-lactamase). The two known mycobacterial BlaRI-type systems in M. tuberculosis (Mtb) and M. abscessus ( Mab) are characterized by BlaR orthologs with conserved zinc metalloprotease domain but lacking an extracellular β-lactam binding domain. BlaIR _Mtb and BlaIR _Mab (renamed BlaIR to reflect inverted genomic organization) regulate β-lactamase expression ( Mtb only) and respiration (both Mtb and Mab). In this study, we have identified a second BlaRI-type system in Mab, MAB_4287-4288 (BlaIR2). Using RT-PCR and EMSA, we established that BlaIR2 _Mab is encoded within a five gene operon, a unique characteristic in BlaRI-type systems, and is auto-regulatory. Identification of putative BlaI2 _Mab binding motifs revealed a predicted regulon comprised of several genes involved in respiration, with some overlap with the BlaI1 _Mab regulon. Finally, our data demonstrated that BlaIR2 _Mab was also induced by the respiration inhibitor clofazimine (CFZ) similarly to BlaIR1 _Mab, with evidence of possible crosstalk between BlaRI systems. Overall, this study established MAB_4287-4288 (BlaIR2 _Mab) as a second BlaRI-type system in Mab, whose role may overlap or intersect that of BlaRI1 _Mab. However, the activation mechanism and full role of BlaIR2 _Mab in Mab stress responses and pathogenesis remains to be elucidated.