12. ANTIMICROBIAL DRUG RESISTANCE IN THE PERSPECTIVE OF BACTERIAL MUTATION by R. D. SINGH1, S. K. MODY1, H. B. PATEL1, SARITA DEVI2, H. A. PATEL1, BHATIYA, S.I.1 AND DESAI, R.R.1

Abstract

Antimicrobial drug resistance (AMR) is a global challenge in treatment and prevention of infectious diseases in man and animals. It has great economic impact due to reduced productivity of life and higher cost of treatment involved. The major causes responsible for AMR are misuse, overuse or improper use of antimicrobials for human and veterinary diseases. Mutation is one of several mechanisms by which bacterial species develop resistance against antimicrobial drug. The bacterial genome mutation leads to either target modification or target alteration. The occurrence of mutation is influenced by several environmental factors as well as intrinsic characteristics of bacterial genome. Gene duplication or amplification and point mutation are type of mutation process responsible for alteration in genetic material of bacteria which provides AMR. Mutation is dynamic, random and variable in nature. It does not occur consistently throughout length of genome. Hypermutable loci showing high mutation rates have been identified in bacteria like H. influenza and N. meningitides. The mutation rate varies under different circumstances. Normal mutation rate in E. coli is 1 per 1010 nucleotides whereas in altered methyl directed mismatch repair system, the rate may increase up to 100-1000 fold times. The survivability and spread of resistant mutant after emergence is critical factor in determining clinical outcome of antimicrobial usage. Intensity and length of duration of selection pressure determines the further survival and propagation of mutants. Mutation frequency and fitness cost are two important factor predicting development of resistance. These parameters provide clues on rate and overall quantum of mutation in bacterial cells. Mutation prevention concentration (MPC) indicates concentration of antimicrobial drugs that prevent the selection of first step resistant mutation in normal population of bacteria whereas mutation selection window (MSW) represents the range of antimicrobial concentration where the selection for resistant bacteria may occur. Mutation thus plays important role in conferring AMR. Understanding the process of mutation and its parameters would broaden future perspectives of research efforts on AMR and its clinical outcome.
KEY WORDS: Antimicrobial drug resistance (AMR), Bacterial mutation, Mutation Prevention Concentration (MPC), Mutation Selection window (MSW).