nalD

NalD is a transcriptional repressor protein found in Pseudomonas aeruginosa. It belongs to the TetR family of transcriptional regulators and functions as a negative regulator of the MexAB-OprM multidrug efflux pump operon.

NalD binds to the promoter region of mexAB-oprM and inhibits transcription, thereby limiting the expression of the MexAB-OprM efflux pump. By reducing pump levels, NalD contributes to lower baseline levels of intrinsic resistance to a range of antibiotics. The activity of NalD, like other TetR family regulators, can be influenced by cellular conditions and mutations that alter its DNA-binding affinity.

Genetically, NalD operates within a regulatory network that modulates MexAB-OprM expression alongside other regulators such as MexR and NalC. Disruption of NalD function—through mutations or other alterations—can relieve repression of mexAB-oprM, leading to overexpression of the efflux pump and increased resistance to multiple antibiotic classes, including beta-lactams and fluoroquinolones. Such nalD mutations have been observed in clinical isolates and are associated with reduced antibiotic susceptibility and treatment challenges in P. aeruginosa infections.

In terms of structure, NalD is a small, dimeric protein typical of the TetR family. It generally comprises a DNA-binding N-terminal helix-turn-helix domain and a C-terminal regulatory domain, with dimerization essential for high-affinity operator binding. The protein’s modular architecture supports ligand-responsive control of DNA binding, a common feature of TetR regulators, enabling dynamic control of mexAB-oprM expression in response to cellular cues.

See also: MexAB-OprM, Pseudomonas aeruginosa, antibiotic resistance, TetR family.