Evolutionary dynamics of methicillin-resistant Staphylococcus aureus within a healthcare system

BackgroundIn the past decade, several countries have seen gradual replacement of endemic multi-resistant healthcare-associated methicillin-resistant Staphylococcus aureus (MRSA) with clones that are more susceptible to antibiotic treatment. One example is Singapore, where MRSA ST239, the dominant clone since molecular profiling of MRSA began in the mid-1980s, has been replaced by ST22 isolates belonging to EMRSA-15, a recently emerged pandemic lineage originating from Europe.ResultsWe investigated the population structure of MRSA in Singaporean hospitals spanning three decades, using whole genome sequencing. Applying Bayesian phylogenetic methods we report that prior to the introduction of ST22, the ST239 MRSA population in Singapore originated from multiple introductions from the surrounding region; it was frequently transferred within the healthcare system resulting in a heterogeneous hospital population. Following the introduction of ST22 around the beginning of the millennium, this clone spread rapidly through Singaporean hospitals, supplanting the endemic ST239 population. Coalescent analysis revealed that although the genetic diversity of ST239 initially decreased as ST22 became more dominant, from 2007 onwards the genetic diversity of ST239 began to increase once more, which was not associated with the emergence of a sub-clone of ST239. Comparative genomic analysis of the accessory genome of the extant ST239 population identified that the Arginine Catabolic Mobile Element arose multiple times, thereby introducing genes associated with enhanced skin colonization into this population.ConclusionsOur results clearly demonstrate that, alongside clinical practice and antibiotic usage, competition between clones also has an important role in driving the evolution of nosocomial pathogen populations.

Electronic supplementary material

The online version of this article (doi:10.1186/s13059-015-0643-z) contains supplementary material, which is available to authorized users.     

The deafness locus (dn) maps to mouse Chromosome 19

The deafness mouse has profound sensorineural hearing loss with degeneration of hair cells soon after birth. The mode of inheritance is recessive, and there are no associated phenotypic anomalies. Thus, this mouse provides a model for recessive, nonsyndromic, prelingual deafness. We have mapped the gene causing deafness in the mouse to Chromosome (Chr) 19 by analysis of 230 intersubspecific backcross progeny. No recombinants were found with the microsatellite marker D19Mit14. The loci for two guanine nucleotide-binding proteins are tightly linked to this marker, and they are being investigated as possible candidate genes. The identification of the defective gene in the mouse will help to explain the mechanism that causes hair cell degeneration and is likely to identify a homologous gene for deafness in humans.     

Cattle,weather and water: mapping Escherichia coli O157:H7 infections in humans in England and Scotland

Entero‐haemorrhagic Escherichia coli O157:H7 is a zoonotic pathogen, responsible for a relatively small number of food poisoning and illness outbreaks each year, when compared with other food‐borne bacteria capable of causing infections in the population. Nevertheless, E. coli O157:H7 is a bacterial pathogen associated with severe human illnesses including bloody diarrhoea and haemolytic uremic syndrome occurring in both outbreak and sporadic settings. In England and Wales approximately 1% of all laboratory‐confirmed cases of food poisoning are the result of E. coli O157:H7; however, in Scotland this figure increases to 3%. When the size of the population is taken into account and the rate of E. coli O157:H7 confirmed cases per 100 000 population is examined, the rate of E. coli 0157:H7 infections in Scotland is much greater than England and Wales. The routes of transmission have changed over time, with new routes of transmission such as farm visits emerging. The prevalence of E. coli O157:H7 has a seasonal dependency, with greater faecal shedding of the organism in the warmer months; this is directly mirrored in the increased reporting of E. coli O157:H7 infection among hospitalized patients. This review attempts to suggest why this phenomenon occurs, paying particular attention to weather, animal movement and private water supplies.     

Evolution of Spore Release Mechanisms in the Saprolegniaceae (Oomycetes): Evidence from a Phylogenetic Analysis of Internal Transcribed Spacer Sequences

Classical studies on spore release within the Saprolegniaceae (Oomycetes) led to the proposition that different mechanisms of sporangial emptying represent steps in an evolutionary transition series. We have reevaluated this idea in a phylogenetic framework using internal transcribed spacer sequences of four genera. These data were compared with the response to osmotic stress exhibited by each taxon.Saprolegniaemerges as the most basal genus, sister toAchlya, Thraustotheca,andDictyuchus. AchlyaandThraustothecaare most closely related, whileDictyuchusappears to have evolved along a separate evolutionary lineage. The resulting phylogenetic framework is consistent with the idea that the mechanism of sporangial emptying exhibited bySaprolegniarepresents the plesiomorphic condition from which the other mechanisms were derived independently. These alternative mechanisms of spore release may have resulted from a small number of mutations that inhibited axonemal development and altered the temporal and spatial expression of lytic enzymes that degrade the sporangial wall.     

Global remodelling of cellular microenvironment due to loss of collagen VII

The mammalian cellular microenvironment is shaped by soluble factors and structural components, the extracellular matrix, providing physical support, regulating adhesion and signalling. A global, quantitative mass spectrometry strategy, combined with bioinformatics data processing, was developed to assess proteome differences in the microenvironment of primary human fibroblasts. We studied secreted proteins of fibroblasts from normal and pathologically altered skin and their post‐translational modifications. The influence of collagen VII, an important structural component, which is lost in genetic skin fragility, was used as model. Loss of collagen VII had a global impact on the cellular microenvironment and was associated with proteome alterations highly relevant for disease pathogenesis including decrease in basement membrane components, increase in dermal matrix proteins, TGF‐β and metalloproteases, but not higher protease activity. The definition of the proteome of fibroblast microenvironment and its plasticity in health and disease identified novel disease mechanisms and potential targets of intervention.     

Quantitative real-time PCR assay for determining transgene copy number in transformed plants

The development of transgenic events can be limited by many factors. These include expression levels, insert stability and inheritance, and the identification of simple insertion events. All of the factors can be related to the copy number of the transgene. Traditionally, copy number has been determined by laborious blotting techniques. We have developed an alternative approach that utilizes the fluorogenic 5' nuclease (TaqMan) assay to quantitatively determine transgene copy level in plants. Using this assay, hundreds of samples can be analyzed per day in contrast to the low throughput encountered with traditional methods. To develop the TaqMan copy number assay, we chose to utilize our highly efficient Agrobacterium-mediated transformation system of maize. This transformation procedure generates predominantly low copy number insertion events, which simplified assay development. We have also successful applied this assay to other crops and transformation systems.     

Urinary bisphenol a concentration and angiography-defined coronary artery stenosis

Background

Bisphenol A is widely used in food and drinks packaging. There is evidence of associations between raised urinary bisphenol A (uBPA) and increased incidence of reported cardiovascular diagnoses.

Methodology/Principal Findings

To estimate associations between BPA exposure and angiographically graded coronary atherosclerosis. 591 patients participating in The Metabonomics and Genomics in Coronary Artery Disease (MaGiCAD) study in Cambridgeshire UK, comparing urinary BPA (uBPA) with grades of severity of coronary artery disease (CAD) on angiography. Linear models were adjusted for BMI, occupational social class and diabetes status. Severe (one to three vessel) CAD was present in 385 patients, 86 had intermediate disease (n = 86) and 120 had normal coronary arteries. The (unadjusted) median uBPA concentration was 1.28 ng/mL with normal coronary arteries, and 1.53 ng/mL with severe CAD. Compared to those with normal coronary arteries, uBPA concentration was significantly higher in those with severe CAD (OR per uBPA SD = 5.96 ng/ml OR = 1.43, CI 1.03 to 1.98, p = 0.033), and near significant for intermediate disease (OR = 1.69, CI 0.98 to 2.94, p = 0.061). There was no significant uBPA difference between patients with severe CAD (needing surgery) and the remaining groups combined.

Conclusions/Significance

BPA exposure was higher in those with severe coronary artery stenoses compared to those with no vessel disease. Larger studies are needed to estimate true dose response relationships. The mechanisms underlying the association remain to be established.