Schematics of native and transplanted two-component signaling pathways. (A) The native pathway consists of a receptor histidine kinase protein, which senses and propagates the signal to a cognate response regulator that regulates gene expression. (B) The envisioned adaptation to the mammalian host. Subscript “hum” indicates human-optimized codon sequence. DNAB, DNA binding. Pconst, constitutive mammalian promoter. P, phosphate; Pmin, minimal mammalian promoter; VP16, VP16 transactivator domain.