Protein profile of the Escherichia coli strain, BW25113, exposed to two novel iron-halide compounds: Fe(Hampy)2Cl4 and Fe(Hampy)2Br4.

The mortality rate and economic burden of infections caused by antimicrobial-resistant pathogens are increasingly higher. This frustrating scenario emphasizes the urgent need for developing new antimicrobial drugs. We have previously addressed this problem by studying the antimicrobial activity of two novel iron-halide complexes, Fe(Hampy)Cl (iron tetrachloride) and Fe(Hampy)Br (iron tetrabromide). Both compounds showed bactericidal and antibiofilm activities against bacteria with an antimicrobial resistance phenotype. Herein, we used a proteomic approach to investigate the proteomic profile of bacterial cells previously exposed to both iron-halide complexes. For this study, the strain, BW25113, was used as a model to facilitate the rapid identification of deregulated proteins. Heat map analysis of the common deregulated proteins highlighted that both complexes caused the downregulation of proteins associated with key metabolic pathways, biofilm formation, cell envelope biogenesis and iron ion binding. In addition, a network study suggested that the most influential proteins of the tetrachloride activity were those involved in the TCA cycle, oxidative phosphorylation, iron ion homeostasis and carbon/secondary metabolism. This protein-protein interaction analysis also hinted that the main drivers of the tetrabromide activity were proteins involved in translation, ribosomal biogenesis and cell motility. The above results strongly suggested how the presence of different halide ligands could be used to generate compounds with potentially different molecular mechanisms. Importantly, the findings of this study can also be used as a reference to compare with the protein profile of bacteria exposed to future variants of the iron-halide complexes.