Impact of transient acquired hypermutability on the inter- and intra-species competitiveness of Pseudomonas aeruginosa.

Once acquired, hypermutation is unrelenting, and in the long-term, leads to impaired fitness due to its cumulative impact on the genome. This raises the question of why hypermutators arise so frequently in microbial ecosystems. In this work, we explore this problem by examining how the transient acquisition of hypermutability affects inter- and intra-species competitiveness, and the response to environmental insults such as antibiotic challenge. We do this by engineering Pseudomonas aeruginosa to allow the expression of an important mismatch repair gene, mutS, to be experimentally controlled over a wide dynamic range. We show that high levels of mutS expression induce genomic stasis (hypomutation), whereas lower levels of induction lead to progressively higher rates of mutation. Whole-genome sequence analyses confirmed that the mutational spectrum of the inducible hypermutator is similar to the distinctive profile associated with mutS mutants obtained from the airways of people with cystic fibrosis (CF). The acquisition of hypermutability conferred a distinct temporal fitness advantage over the wild-type P. aeruginosa progenitor strain, in both the presence and the absence of an antibiotic selection pressure. However, over a similar time-scale, acquisition of hypermutability had little impact on the population dynamics of P. aeruginosa when grown in the presence of a competing species (Staphylococcus aureus). These data indicate that in the short term, acquired hypermutability primarily confers a competitive intra-species fitness advantage.

Digital health is a cultural transformation of traditional healthcare.

Under the term "digital health", advanced medical technologies, disruptive innovations and digital communication have gradually become inseparable from providing best practice healthcare. While the cost of treating chronic conditions is increasing and doctor shortages are imminent worldwide, the needed transformation in the structure of healthcare and medicine fails to catch up with the rapid progress of the medical technology industry. This transition is slowed down by strict regulations; the reluctance of stakeholders in healthcare to change; and ignoring the importance of cultural changes and the human factor in an increasingly technological world. With access and adoption of technology getting higher, the risk of patients primarily turning to an accessible, but unregulated technological solution for their health problem is likely to increase. In this paper, we discuss how the old paradigm of the paternalistic model of medicine is transforming into an equal level partnership between patients and professionals and how it is aided and augmented by disruptive technologies. We attempt to define what digital health means and how it affects the status quo of care and also the study design in implementing technological innovations into the practice of medicine.