Abstract Perception by each individual organism of its surrounding environment is a key factor for survival. In a constantly changing environment, the ability to assess nutrient sources and potentially stressful situations constitute the main basis for ecological adaptability. Transcription regulators are key decision-making proteins that mediate the communication between environmental conditions and DNA transcription through a multifaceted network. The parallel study of these regulators across microbial organisms adapted to contrasting biotopes constitutes an unexplored approach to understand the evolution of genomes plasticity and cell's functioning. We present here a reassessment of bacterial helix-turn-helix regulators diversity in different organisms from a multidisciplinary perspective, on the verge of the interface that links metabolism, ecology and phylogeny, and further sustained by a statistically-based approach. The present revision brought to light the evidence of patterns among families of regulators, suggesting that multiple selective forces modulate the number and kind of regulators present in a given genome. Besides being an important step towards understanding the adaptive traits that influence the microbial responses to the varying environment on the very first and most prevalent line of reaction, the transcription of DNA, this approach is a promising tool to define biological trends across proteomic databases. Keywords: ecological adaptability; helix-turn-helix; transcriptional regulators.