Evidence for Induction of Integron-Based Antibiotic Resistance by the SOS Response in a Clinical Setting

Bacterial resistance to β-lactams may rely on acquired β-lactamases encoded by class 1 integron-borne genes. Rearrangement of integron cassette arrays is mediated by the integrase IntI1. It has been previously established that integrase expression can be activated by the SOS response in vitro, leading to speculation that this is an important clinical mechanism of acquiring resistance. Here we report the first in vivo evidence of the impact of SOS response activated by the antibiotic treatment given to a patient and its output in terms of resistance development. We identified a new mechanism of modulation of antibiotic resistance in integrons, based on the insertion of a genetic element, the gcuF1 cassette, upstream of the integron-borne cassette blaOXA-28 encoding an extended spectrum β-lactamase. This insertion creates the fused protein GCUF1-OXA-28 and modulates the transcription, the translation, and the secretion of the β-lactamase in a Pseudomonas aeruginosa isolate (S-Pae) susceptible to the third generation cephalosporin ceftazidime. We found that the metronidazole, not an anti-pseudomonal antibiotic given to the first patient infected with S-Pae, triggered the SOS response that subsequently activated the integrase IntI1 expression. This resulted in the rearrangement of the integron gene cassette array, through excision of the gcuF1 cassette, and the full expression the β-lactamase in an isolate (R-Pae) highly resistant to ceftazidime, which further spread to other patients within our hospital. Our results demonstrate that in human hosts, the antibiotic-induced SOS response in pathogens could play a pivotal role in adaptation process of the bacteria

Evidence of positive selection associated with placental loss in tiger sharks

Background: All vertebrates initially feed their offspring using yolk reserves. In some live-bearing species these yolk reserves may be supplemented with extra nutrition via a placenta. Sharks belonging to the Carcharhinidae family are all live-bearing, and with the exception of the tiger shark (Galeocerdo cuvier), develop placental connections after exhausting yolk reserves. Phylogenetic relationships suggest the lack of placenta in tiger sharks is due to secondary loss. This represents a dramatic shift in reproductive strategy, and is likely to have left a molecular footprint of positive selection within the genome. Results: We sequenced the transcriptome of the tiger shark and eight other live-bearing shark species. From this data we constructed a time-calibrated phylogenetic tree estimating the tiger shark lineage diverged from the placental carcharhinids approximately 94 million years ago. Along the tiger shark lineage, we identified five genes exhibiting a signature of positive selection. Four of these genes have functions likely associated with brain development (YWHAE and ARL6IP5) and sexual reproduction (VAMP4 and TCTEX1D2). Conclusions: Our results indicate the loss of placenta in tiger sharks may be associated with subsequent adaptive changes in brain development and sperm production

URSIDAE LOCOMOTION: RIGHT DOWN TO THE “BEAR BONES”

The plantigrade posture refers to species that have their entire foot, from heel to toes, on the ground. The Order Carnivora contains terrestrial families of both digitigrade (stand on their toes) and plantigrade species, and includes a wide representation of locomotor behaviours. Bears (family Ursidae) are the only group of large plantigrade species in Carnivora. This makes ursids a unique family as they are relatively distinct from other mammals. Ursidae morphology is at the extreme plantigrade end of the posture spectrum, therefore representative of plantigrade animals, despite their significantly larger size than other carnivoran species. Within Ursidae there are eight extant bear species; these species range in size, diet, and locomotor behaviour. There have been many previous studies of the relationship between morphology and locomotor behaviour in Carnivora, all of which have included both digitigrade and plantigrade species. Plantigrade species, particularly bears, are often noted as outliers in these studies. However, it’s possible that the morphological differences related to posture are confounding the results. The aims of this dissertation were to characterise the locomotion of a representative plantigrade carnivoran (grizzly bears; Ursus arctos horribilis), and to determine if a model using bone morphology of only plantigrade species could increase accuracy of estimating locomotor behaviour in extinct plantigrade species. The first chapter of my dissertation is a detailed description of the design, construction, and calibration of a force plate. This force plate was custom built to be used with grizzly bears, although it is suitable for both smaller and larger animals. Chapters 2 and 3 are analyses of grizzly bear locomotion. This includes a description of the gaits used and the ground reaction forces produced by the bears, as well as a more detailed analysis of the forelimb joint dynamics across speed. The fourth chapter of my dissertation is a morphometric analysis of forelimb bones from 44 extant species of plantigrade carnivorans, plus specimens from two extinct genera. Overall this dissertation is a comprehensive view of the locomotion of a representative plantigrade species, incorporated into an evolutionary framework by bone shape analysis of several other plantigrade families.doctoral, Ph.D., Biology -- University of Idaho - College of Graduate Studies, 201

Brainhack: Developing a culture of open, inclusive, community-driven neuroscience

Brainhack is an innovative meeting format that promotes scientific collaboration and education in an open, inclusive environment. This NeuroView describes the myriad benefits for participants and the research community and how Brainhacks complement conventional formats to augment scientific progress