Metallo β lactamase: reactivity and site directed evolution pathways addressed by computational approaches

The indiscriminate prescription of antibiotics by physicians, along with their incorrect use [1] 1 has increased the exposition of bacteria to antibiotics, and thus has created a favorable environment for the Darwinian evolution of resistant strains [2]. Further increase of drug resistance is caused by the unnecessary massive use of antibiotics (70% of the total market is in the US!) to animals crammed into the unhygienic crowded quarters of factories [3, 4]. Diseases like tubercolosis, gonorrhea, malaria, and childhood ear infections, are increasingly becoming hard to treat with antibiotic drugs, posing serious concern in the human public health [5, 6]. The problem is even more serious if one considers that already in 70’s and 80’s that modification of the chemical structure of the already known antibiotics turned out to be exhausted and, at the same time, pharmacological companies decided not design of totally new antibiotics [2].