Quantifying the Adaptive Potential of an Antibiotic Resistance Enzyme

For a quantitative understanding of the process of adaptation, we need to understand its “raw material,” that is, the frequency and fitness effects of beneficial mutations. At present, most empirical evidence suggests an exponential distribution of fitness effects of beneficial mutations, as predicted for Gumbel-domain distributions by extreme value theory. Here, we study the distribution of mutation effects on cefotaxime (Ctx) resistance and fitness of 48 unique beneficial mutations in the bacterial enzyme TEM-1 β-lactamase, which were obtained by screening the products of random mutagenesis for increased Ctx resistance. Our contributions are threefold. First, based on the frequency of unique mutations among more than 300 sequenced isolates and correcting for mutation bias, we conservatively estimate that the total number of first-step mutations that increase Ctx resistance in this enzyme is 87 [95% CI 75–189], or 3.4% of all 2,583 possible base-pair substitutions. Of the 48 mutations, 10 are synonymous and the majority of the 38 non-synonymous mutations occur in the pocket surrounding the catalytic site. Second, we estimate the effects of the mutations on Ctx resistance by determining survival at various Ctx concentrations, and we derive their fitness effects by modeling reproduction and survival as a branching process. Third, we find that the distribution of both measures follows a Fréchet-type distribution characterized by a broad tail of a few exceptionally fit mutants. Such distributions have fundamental evolutionary implications, including an increased predictability of evolution, and may provide a partial explanation for recent observations of striking parallel evolution of antibiotic resistance

Last mile logistics in smart cities: An IT platform for vehicle sharing and routing

Due to the current remarkable growth of e-commerce, the last mile logistics has become a relevant problem. In this paper, the main issues of the last mile logistics in a smart city context are introduced. We propose a solution based on a shared Information Technology (IT) platform that needs no material investments. The principle of resource pooling is applied to the sharing of heterogeneous vehicles in the urban network. In particular, an IT platform powered by an optimization algorithm is proposed to allow couriers to make their deliveries more efficiently, that is, to reduce the total distance covered by the vehicles. This was achieved through the development of four software modules: an ETL, an optimizer, a web application and a map displayer. First results are promising, but further investigations should be done in order to evaluate more accurately the expected benefits and the possible positive externalities such as improvement of air quality in the city