Variation in bacterial pathotype is consistent with the sit-and-wait hypothesis.

The sit-and-wait hypothesis predicts that bacteria can become more virulent when they survive and transmit outside of their hosts due to circumventing the costs of host mortality. While this hypothesis is largely supported theoretically and through comparative analysis, experimental validation is limited. Here we test this hypothesis in , an opportunistic zoonotic pig pathogen, where a pathogenic ecotype proliferated during the change to intensive pig farming that amplifies opportunities for fomite transmission.

Evaluating the impact of genomic epidemiology of methicillin-resistant (MRSA) on hospital infection prevention and control decisions.

Genomic epidemiology enhances the ability to detect and refute methicillin-resistant (MRSA) outbreaks in healthcare settings, but its routine introduction requires further evidence of benefits for patients and resource utilization. We performed a 12 month prospective study at Cambridge University Hospitals NHS Foundation Trust in the UK to capture its impact on hospital infection prevention and control (IPC) decisions. MRSA-positive samples were identified via the hospital microbiology laboratory between November 2018 and November 2019.

Defining metrics for whole-genome sequence analysis of MRSA in clinical practice.

Bacterial sequencing will become increasingly adopted in routine microbiology laboratories. Here, we report the findings of a technical evaluation of almost 800 clinical methicillin-resistant (MRSA) isolates, in which we sought to define key quality metrics to support MRSA sequencing in clinical practice. We evaluated the accuracy of mapping to a generic reference versus clonal complex (CC)-specific mapping, which is more computationally challenging.

Genomic surveillance of ST131 identifies local expansion and serial replacement of subclones.

sequence type 131 (ST131) is a pandemic clone that is evolving rapidly with increasing levels of antimicrobial resistance. Here, we investigated an outbreak of ST131 producing extended spectrum β-lactamases (ESBLs) in a long-term care facility (LTCF) in Ireland by combining data from this LTCF (=69) with other Irish (=35) and global (=690) ST131 genomes to reconstruct the evolutionary history and understand changes in population structure and genome architecture over time. This required a combination of short- and long-read genome sequencing, assembly, read mapping, ESBL gene screening, plasmid alignment and temporal phylogenetics.

Genomic surveillance of Escherichia coli in municipal wastewater treatment plants as an indicator of clinically relevant pathogens and their resistance genes.

We examined whether genomic surveillance of Escherichia coli in wastewater could capture the dominant E. coli lineages associated with bloodstream infection and livestock in the East of England, together with the antibiotic-resistance genes circulating in the wider E. coli population.

Rapid sequencing of MRSA direct from clinical plates in a routine microbiology laboratory.

Background: Routine sequencing of MRSA could bring about significant improvements to outbreak detection and investigation. Sequencing is commonly performed using DNA extracted from a pure culture, but overcoming the delay associated with this step could reduce the time to infection control interventions.

Objectives: To develop and evaluate rapid sequencing of MRSA using primary clinical cultures.

HCMV latency: what regulates the regulators?

Human cytomegalovirus (HCMV) latency and reactivation is regulated by the chromatin structure at the major immediate early promoter (MIEP) within myeloid cells. Both cellular and viral factors are known to control this promoter during latency, here we will review the known mechanisms for MIEP regulation during latency. We will then focus on the virally encoded G-protein coupled receptor, US28, which suppresses the MIEP in early myeloid lineage cells.

Whole genome sequencing of ESBL-producing Escherichia coli isolated from patients, farm waste and canals in Thailand.

Background: Tackling multidrug-resistant Escherichia coli requires evidence from One Health studies that capture numerous potential reservoirs in circumscribed geographic areas.

Methods: We conducted a survey of extended β-lactamase (ESBL)-producing E. coli isolated from patients, canals and livestock wastewater in eastern Thailand between 2014 and 2015, and analyzed isolates using whole genome sequencing.

Genomic surveillance reveals low prevalence of livestock-associated methicillin-resistant Staphylococcus aureus in the East of England.

Livestock-associated methicillin-resistant Staphylococcus aureus (LA-MRSA) is an emerging problem in many parts of the world. LA-MRSA has been isolated previously from animals and humans in the United Kingdom (UK), but the prevalence is unknown. The aim of this study was to determine the prevalence and to describe the molecular epidemiology of LA-MRSA isolated in the East of England (broadly Cambridge and the surrounding area).

Genome-based characterization of hospital-adapted Enterococcus faecalis lineages.

Vancomycin-resistant Enterococcus faecalis (VREfs) is an important nosocomial pathogen(1,2). We undertook whole genome sequencing of E. faecalis associated with bloodstream infection in the UK and Ireland over more than a decade to determine the population structure and genetic associations with hospital adaptation.

Genome-based characterization of hospital-adapted lineages.

Vancomycin-resistant (VREfs) is an important nosocomial pathogen1,2. We undertook whole genome sequencing of associated with bloodstream infection in the UK and Ireland over more than a decade to determine the population structure and genetic associations with hospital adaptation. Three lineages predominated in the population, two of which (L1 and L2) were nationally distributed, and one (L3) geographically restricted.

'Add, stir and reduce': Yersinia spp. as model bacteria for pathogen evolution.

Pathogenic species in the Yersinia genus have historically been targets for research aimed at understanding how bacteria evolve into mammalian pathogens. The advent of large-scale population genomic studies has greatly accelerated the progress in this field, and Yersinia pestis, Yersinia pseudotuberculosis and Yersinia enterocolitica have once again acted as model organisms to help shape our understanding of the evolutionary processes involved in pathogenesis. In this Review, we highlight the gene gain, gene loss and genome rearrangement events that have been identified by genomic studies in pathogenic Yersinia species, and we discuss how these findings are changing our understanding of pathogen evolution.

Microbial sequencing to improve individual and population health.

Recent advances in sequencing technologies are changing the face of infectious disease investigation and control. Personalized anti-infective therapies and surveillance of emergent pathogen outbreaks are just two examples of the potential benefits of merging the fields of genomics and infectious diseases.

Efficacy and safety of high-dose peanut oral immunotherapy with factors predicting outcome.

Background: Peanut allergy is severe and rarely resolves.

Objective: To test the efficacy and safety of a new oral immunotherapy (OIT) protocol for peanut allergy.

Method: Twenty-two peanut-allergic children underwent oral challenge.

Genetics of pulmonary arterial hypertension: do the molecular findings have translational value?

Pulmonary arterial hypertension (PAH) is usually a devastating condition with a poor prognosis. Nearly 10 years ago, the underlying molecular basis of heritable PAH was elucidated with the identification of mutations in the gene encoding the bone morphogenetic protein type II receptor (BMPR-II). This discovery is now beginning to suggest novel approaches to therapy in heritable PAH.

Alanine infusion during hypoglycaemia partly supports cognitive performance in healthy human subjects.

Aim: To investigate the potential for the non-glucose metabolic substrate alanine to support brain function during glucose deprivation in man.

Methods: Seven healthy men were studied on two occasions using a hyperinsulinaemic glucose clamp to lower arterialized plasma glucose to 2.5 mmol/l, in the presence of either 2 mmol/kg/h alanine infusion or saline, measuring counter-regulatory hormonal responses, symptoms generated and cognitive function with a mini-battery of tests sensitive to hypoglycaemia.