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Chapter 7 : Antibiotic Resistance
This chapter focuses on the genetic and evolutionary aspects of antibiotic resistance, and how an unintended global experiment in selection has taught us about genetic variation and evolution in the bacteria. An antibiotic may fail to reach its intended target, for example, because it cannot cross the cell wall and get inside the bacterium. Genetic alterations can cause previously susceptible bacteria to become antibiotic resistant. This is a major reason why many antibiotics are ineffective against gram-negative bacteria, and why pharmaceutical companies have devoted great research efforts to developing variants of successful antibiotics with different activity spectra. The genetic pathways by which bacteria can evolve antibiotic resistance can be broadly divided into two classes: (i) those where genetic alterations reduce the effective interaction between the antibiotic and its target in the bacterial cell and (ii) those where genetic alterations reduce the chemical effectiveness of the antibiotic molecule itself. An important aspect to consider in the evolution of antibiotic resistance is the source of the genetic alteration responsible for the resistance. The global significance of horizontal gene transfer in providing the raw material for bacterial evolution in general, and antibiotic resistance specifically, is one of the major lessons we are still learning from our use of antibiotics. One way to evolve antibiotic resistance is by mutating the gene coding for the target of the antibiotic. A resistance phenotype can also be generated by any mechanism that inactivates the antibiotic.