The recent expansion of multidrug-resistant (MDR) pathogens poses significant challenges in treating healthcare-associated infections. Although antibacterial resistance occurs through numerous mechanisms, including enzymatic inactivation of drugs, lack of pro-drug activation, and drug target alteration, increased active efflux of the drugs is a major concern, especially because a single species of efflux pump can produce simultaneous resistance to several drugs. One of the best-studied efflux pumps is the TtgABC, a tripartite RND efflux pump implicated in the intrinsic antibiotic resistance in \textit{Pseudomonas putida} DOT-T1E. Expression of the TtgABC gene is down-regulated by the HTH-type transcriptional repressor TtgR. The association of effectors with the TtgR-DNA complex leads to the dissociation of TtgR from the operator region, allowing transcription. Therefore, studies that evaluate the action of these regulators are important for understanding the peculiarities of the resistance mechanisms promoted by the efflux pumps. In this context, by employing quantum chemistry methods based on density functional theory (DFT) within the MFCC approach, we investigated the coupling profiles of the transcriptional regulator TtgR in complex with quercetin (QUE), a natural polyphenolic flavonoid, tetracycline (TAC), and chloramphenicol (CLM), two broad-spectrum antimicrobial agents. Our quantum biochemical, computational results show the [i] convergence radius, [ii] total binding energy, [iii] relevance (energetically) of the ligands regions, and [iv] most important amino acids residues of the TtgR-QUE/TAC/CLM complexes, pointing out distinctions and similarities among them. These findings improve our understanding of the mechanism of binding of effectors and facilitate the development of new chemicals targeting TtgR, helping in the fight against the rise of resistance to antimicrobial drugs.