Abstract
Infections caused by MDR (Multi-drug resistant) strains are increasing with
time due to the selection pressure posed by the use of antibiotics. The mechanisms that
confer antibiotic resistance to bacteria are gene mutation, change in cell envelop, over
expression of efflux pumps and biofilm formation. Drug development for MDR has
become one of the major challenges globally. MDR infections associated with health
care facilities are difficult to treat due to the limited therapeutic approaches or even no
treatment options. Therefore, there is an emergency to develop new therapeutic
approaches against MDR pathogens. It is possible to identify proteins that are
responsible for the survival of pathogenic MDR bacteria for the purpose of drug
discovery. Rational-structure based drug design is an inventive process of finding new
drug targets, which relies on the knowledge of three-dimensional structure of biological
targets. The three-dimension structure is obtained by high throughput techniques such
as X-ray diffraction (XRD), Nuclear Magnetic Resonance (NMR) and Cryo-electron
microscopy (Cryo- EM). Structure biology plays an important role in the
characterization of new therapeutic targets and assessment of drug targets.
Computational methods boost drug development and discovery process against MDR
pathogens and analyse efficient therapies.
Keywords: Antibiotic resistance, Cryo-EM, Drug discovery, Multidrug resistance, NMR, Rational structure based drug design, Structure biology, X-ray diffraction.