Epigenetic inheritance based evolution of antibiotic resistance in bacteria
Authors- Mike Adam, Bhuvana Murali, Nicole O Glenn and S Steven Potter
The evolution of antibiotic resistance in bacteria is a topic of paramount medical Importance. Evolution is the result of natural selection acting on variant phenotypes. Here is an isogenic population showing phenotypic variation, that is mediated by epigenetic inheritance.
When working with E.coli that was exposed to low concentrations of antibiotics, it became evident that within that isogenic group of microorganisms, there were heritable variations in the pattern of gene expression.
The antibiotics ampicillin, tetracycline and nalidixic acid act by inhibiting cell wall synthesis, protein synthesis and DNA synthesis, respectively. When these microorganisms were grown on antibiotic containing media successively, their survival rates were too high that it couldn’t be due to spontaneous DNA mutation. In addition, resistance levels could be ramped higher by successive exposures to increasing antibiotic concentrations. Genes, whose altered expression might increase survival, were tested by driving constitutive over-expression and determining antibiotic resistance. Three types of resistance genes were identified. The endogenous β-lactamase gene represented a cryptic gene- normally inactive, but when expressed becomes ampicillin resistance. The glutamate decarboxylase gene, in contrast, is normally expressed, but when over expressed has the capacity to increase ampicillin resistance. Finally, the DAM methylase gene regulates the expression of other genes, including multidrug efflux pumps. The semi-stable epigenetic inheritance is mediated by DNA methylation.
Pridhuvi Thavaraj
I.D number 41475937
The evolution of antibiotic resistance in bacteria is a topic of paramount medical Importance. Evolution is the result of natural selection acting on variant phenotypes. Here is an isogenic population showing phenotypic variation, that is mediated by epigenetic inheritance.
When working with E.coli that was exposed to low concentrations of antibiotics, it became evident that within that isogenic group of microorganisms, there were heritable variations in the pattern of gene expression.
The antibiotics ampicillin, tetracycline and nalidixic acid act by inhibiting cell wall synthesis, protein synthesis and DNA synthesis, respectively. When these microorganisms were grown on antibiotic containing media successively, their survival rates were too high that it couldn’t be due to spontaneous DNA mutation. In addition, resistance levels could be ramped higher by successive exposures to increasing antibiotic concentrations. Genes, whose altered expression might increase survival, were tested by driving constitutive over-expression and determining antibiotic resistance. Three types of resistance genes were identified. The endogenous β-lactamase gene represented a cryptic gene- normally inactive, but when expressed becomes ampicillin resistance. The glutamate decarboxylase gene, in contrast, is normally expressed, but when over expressed has the capacity to increase ampicillin resistance. Finally, the DAM methylase gene regulates the expression of other genes, including multidrug efflux pumps. The semi-stable epigenetic inheritance is mediated by DNA methylation.
Pridhuvi Thavaraj
I.D number 41475937
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