Abstract
Resistance to antibiotics is an important and timely problem of contemporary medicine. Rapid evolution of resistant bacteria calls for new preventive measures to slow down this process, and a longer-term progress cannot be achieved without a good understanding of the mechanisms through which drug resistance is acquired and spreads in microbial populations. Here, we discuss recent experimental and theoretical advances in our knowledge how the dynamics of microbial populations affects the evolution of antibiotic resistance . We focus on the role of spatial and temporal drug gradients and show that in certain situations bacteria can evolve de novo resistance within hours. We identify factors that lead to such rapid onset of resistance and discuss their relevance for bacterial infections.
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Notes
- 1.
This can be achieved experimentally by serially diluting the culture when it reaches saturation, or by continuously diluting it in a chemostat.
- 2.
This is true as long as \(F \gg 1/N\).
- 3.
See also earlier work (Kepler and Perelson 1998) on HIV infections.
- 4.
Note that this value is much less than D measured in water or agar-based gels often used to study the diffusion of biomolecules (Meulemans et al. 1989).
- 5.
We assumed that the concentration was 5× higher than the experimentally determined 3–5 μg/ml, following a single dose of 80 mg (Barclay et al. 1996). The actual concentration may be lower—drug binding to serum proteins lowers the effective concentration of the drug, see e.g. (Bergan 1981; Rowland 1995). Reference (Nickel et al. 1985) claims 8 μg/ml in the plasma, and sputum concentrations can be even lower (Honeybourne 1994). All this can promote the evolution of resistance.
- 6.
We take the maximal growth rate g = 0.34 \({\text{h}}^{ - 1}\) and a lower removal rate d = 0.1 than before because the tissue is not perfused and bacteria are less likely to be removed by the immune system.
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Acknowledgements
I thank Rosalind Allen (Edinburgh) and Philip Greulich (Cambridge) for discussions, and Johannes Brennecke (Edinburgh) for reading the manuscript and many helpful suggestions. Financial support of the Royal Society of Edinburgh is acknowledged.
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Waclaw, B. (2016). Evolution of Drug Resistance in Bacteria. In: Leake, M. (eds) Biophysics of Infection. Advances in Experimental Medicine and Biology, vol 915. Springer, Cham. https://doi.org/10.1007/978-3-319-32189-9_5
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