Evolutionary trajectories are constrained by tradeoffs when mutations that benefit one life history trait incur fitness costs in other traits. As resistance to tetracycline antibiotics by increased efflux can be associated with a 10%, or more, increase in length of the Escherichia coli chromosome, we sought costs of resistance associated with doxycycline. However, it was difficult to identify any because E.coli's growth rate (r), carrying capacity (K) and drug efflux rate increased during evolutionary experiments where E.coli was exposed to doxycycline. Moreover, these improvements remained following drug withdrawal. We sought mechanisms for this seemingly unconstrained adaptation particularly as these traits ought to tradeoff according to rK selection theory. Using prokaryote and eukaryote microbes, including clinical pathogens, we therefore show r and K can tradeoff, but need not, because of 'rK trade-ups'. r and K only tradeoff in sufficiently carbon-rich environments where growth is inefficient.We then used E. coli ribosomal RNA (rrn) knockouts to determine specific mutations, namely changes in rrn operon copy number, than can simultaneously maximise r and K. The optimal genome has fewer operons, and therefore fewer functional ribosomes, than the ancestral strain. It is, therefore, unsurprising for r-adaptation in the presence of a ribosome-inhibiting antibiotic, doxycycline, to also increase population size. Although E. coli can evolve to grow faster and to larger population sizes in the presence of antibiotics when compared to their absence, we found two costs to this improvement: an elongated lag phase and the loss of stress protection genes.
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IntroductionTradeoffs lie at the heart of a cross-kingdom research effort that seeks to explain how biodiversity is generated and maintained. [1][2][3][4][5] Two traits engage in an evolutionary tradeoff when beneficial mutations for one trait are deleterious for the other, and vice versa, and many theories agree 2,[6][7][8][9][10][11] that genetic polymorphisms are maintained when tradeoffs have an appropriate geometry. Less clear, however, are the physical, chemical and physiological forces that create tradeoffs in the first place 12 and tradeoffs needed for the theories to work can be difficult to isolate in practise. [13][14][15][16][17][18] It is essential for medicine that we understand tradeoffs. The term 'superbug' refers to a pathogenic microorganism that resists treatment by antibiotics with no apparent cost, or tradeoff, in terms of its pathogenicity. An evolutionary route to superbug status is thought to occur when a pathogen first adopts costly drug resistance mutations, a process that sees resistance traded against proliferation rate in antibiotic-free environments. Thereafter, other mutations compensate for those costs, yielding strains that are both drug resistant and capable of rapid proliferation. 19, 20 Tradeoffs are, however, sometimes observed in pathogens. A genomic study of a clinical pathogen using several antibiotic classes 21 showed res...
