Chapter 21 : The Biological Cost of Antibiotic Resistance

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This chapter focuses on the impact of antibiotic resistance caused by chromosomal mutations on bacterial fitness. An approach to estimate the biological costs associated with resistance is to use epidemiological data to prospectively follow the rate at which a patient infected with a resistant or susceptible bacterial strain transmits it to other people. Such experiments would allow one to measure the basic reproductive number, which is the most relevant parameter to use when predicting the relative rate of spread of the resistant and susceptible bacteria. Chromosomal mutations alter the intracellular level of the transcriptional regulator molecule ppGpp, which might cause additional pleiotrophic fitness effects. Certain mutational alterations in ribosomal protein S12 (encoded by the rpsL gene) causing streptomycin resistance reduce translational efficiency. In isoniazid-resistant , mutants with decreased fitness can be compensated by overproduction of another enzyme that may substitute for the defective catalase. But the most common compensation mechanism is restoration of the function itself, either by intragenic or extragenic mutations. A final implication emerging from studies of fitness costs and their genetic compensation concerns the development of new antibiotics. At present, the key parameter from a resistance development point of view that is considered by drug developers is the rate of appearance of the initial resistance mutation (or plasmid). Even though these rates do influence the rate of resistance development, their importance might be overestimated.

Citation: Andersson D, Patin S, Nilsson A, Kugelberg E. 2007. The Biological Cost of Antibiotic Resistance, p 339-348. In Bonomo R, Tolmasky M (ed), Enzyme-Mediated Resistance to Antibiotics. ASM Press, Washington, DC. doi: 10.1128/9781555815615.ch21
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Generic image for table
Table 21.1

Examples of cases in which biological costs of chromosomal resistances have been estimated

Citation: Andersson D, Patin S, Nilsson A, Kugelberg E. 2007. The Biological Cost of Antibiotic Resistance, p 339-348. In Bonomo R, Tolmasky M (ed), Enzyme-Mediated Resistance to Antibiotics. ASM Press, Washington, DC. doi: 10.1128/9781555815615.ch21
Generic image for table
Table 21.2

Examples of cases in which genetic compensation of fitness cost caused by chromosomal mutations has been demonstrated or inferred

Citation: Andersson D, Patin S, Nilsson A, Kugelberg E. 2007. The Biological Cost of Antibiotic Resistance, p 339-348. In Bonomo R, Tolmasky M (ed), Enzyme-Mediated Resistance to Antibiotics. ASM Press, Washington, DC. doi: 10.1128/9781555815615.ch21

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