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. 1 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...

Microbial electrosynthesis is the process of supplying electrons to microorganisms to reduce CO2 and yield industrially relevant products. Such systems are limited by their requirement for high currents, resulting in challenges to cell survival. Electrofermentation is an electron-efficient form of microbial electrosynthesis in which a small cathodic or anodic current is provided to a culture to alter the oxidation–reduction potential of the medium and, in turn, alter microbial metabolism. This approach has been successfully utilised to increase yields of diverse products including biogas, butanediol and lactate. Biomass conversion to lactate is frequently facilitated by ensiling plant biomass with homofermentative lactic acid bacteria. Although most commonly used as a preservative in ensiled animal feed, lactate has diverse industrial applications as a precursor for the production of probiotics, biofuels, bioplastics and platform chemicals. Lactate yields by lactic acid bacteria (LAB) are constrained by a number of redox limitations which must be overcome while maintaining profitability and sustainability. To date, electrofermentation has not been scaled past laboratory- or pilot-stage reactions. The increasing ease of genetic modification in a wide range of LAB species may prove key to overcoming some of the pitfalls of electrofermentation at commercial scale. This review explores the history of electrofermentation as a tool for controlling redox balance within bacterial biocatalysts, and the potential for electrofermentation to increase lactate production from low-value plant biomass.

10Tradeoffs between life history traits impact diverse biological phenomena, including the mainte-11 nance of biodiversity. We sought to study two canonical tradeoffs in a model host-parasite system 12 consisting of bacteriophage lambda and Escherichia coli: i) parasite resistance for growth and ii) 13 phage infectivity for host-range. We report that these previously hypothesised tradeoffs are, in 14 fact, tradeups. While the observation of tradeups was surprising, they should be expected be-15 cause if traits X and Y tradeoff, so too traits Y and Z, then X and Z will tradeup. By considering 16 five different E. coli trait correlations we uncovered several tradeups and tradeoffs. Using math-17 ematical models, we establish that tradeups need not inhibit biodiversity, as previously thought, 18 and can help maintain it through high-dimensional trait interactions. We provide a mechanis-19 tic explanation for how tradeups emerge and give reasons for why tradeups can even evolve in 20 well-adapted genomes. 21 All data will be posted at https://github.com/rebear217 and mirrored at 22 http://people.exeter.ac.uk/reb217/rebHomePage/data.html on acceptance. 23 24Life history tradeoffs and parasitism are key to our understanding of biodiversity. Different theoretical 25 frameworks 1-4 predict, quite consistently, that if improvements in one trait come with costs in a second 26 trait and if the geometry of that cost has the right form, polymorphisms are maintained. At its logical limit, 27 this suggests tradeoff geometries might be inferred from biodiversity patterns. 4 Infection by parasites is a 28 key driver of genetic diversity and one parasitism tradeoff is central to our understanding of how parasites 29 target their hosts: the host-range tradeoff (HRTO). The HRTO postulates that if a parasite is efficient at 30 targeting one host, it will be inefficient at targeting others. As a result, a lock and key interaction should 31 describe host-parasite interactions 5-7 whereby each parasitic 'key' can only 'unlock' a subset of hosts. 32 Phage therapy represents an important potential adjuvant to antibiotic therapy for life-threatening dis-33 eases 8-10 and tradeoffs are important for the future success of phage therapy. For if a pathogenic bacterium 34 evolves that is able to evade all the phage that it is currently susceptible to, that bacterium will no longer 35 be treatable by phage. However, a postulated cost of resistance tradeoff 11 (CORT) whereby increases in 36 phage resistance come only with reductions in bacterial growth rate suggests that such highly-resistant 37 bacteria, which are observed in patients, 9 will be poor replicators. 38 Given the large number of postulated tradeoffs in the literature [12][13][14][15][16][17][18][19][20] and their importance in ecology and 39 medicine, we used an in vitro coevolutionary model system to test for the presence of (1) the parasite's 40 HRTO and (2) a bacterial CORT. We also tested for (3) the rate-yield tradeoff 21 (RYTO) whereby bacteria 41 that ...

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