Evolution of two distinct phylogenetic lineages of the emerging human pathogen Mycobacterium ulcerans

<p>Abstract</p> <p>Background</p> <p>Comparative genomics has greatly improved our understanding of the evolution of pathogenic mycobacteria such as <it>Mycobacterium tuberculosis</it>. Here we have used data from a genome microarray analysis to explore insertion-deletion (InDel) polymorphism among a diverse strain collection of <it>Mycobacterium ulcerans</it>, the causative agent of the devastating skin disease, Buruli ulcer. Detailed analysis of large sequence polymorphisms in twelve regions of difference (RDs), comprising irreversible genetic markers, enabled us to refine the phylogenetic succession within <it>M. ulcerans</it>, to define features of a hypothetical <it>M. ulcerans </it>most recent common ancestor and to confirm its origin from <it>Mycobacterium marinum</it>.</p> <p>Results</p> <p><it> M. ulcerans </it>has evolved into five InDel haplotypes that separate into two distinct lineages: (i) the "classical" lineage including the most pathogenic genotypes – those that come from Africa, Australia and South East Asia; and (ii) an "ancestral" <it>M. ulcerans </it>lineage comprising strains from Asia (China/Japan), South America and Mexico. The ancestral lineage is genetically closer to the progenitor <it>M. marinum </it>in both RD composition and DNA sequence identity, whereas the classical lineage has undergone major genomic rearrangements.</p> <p>Conclusion</p> <p>Results of the InDel analysis are in complete accord with recent multi-locus sequence analysis and indicate that <it>M. ulcerans </it>has passed through at least two major evolutionary bottlenecks since divergence from <it>M. marinum</it>. The classical lineage shows more pronounced reductive evolution than the ancestral lineage, suggesting that there may be differences in the ecology between the two lineages. These findings improve the understanding of the adaptive evolution and virulence of <it>M. ulcerans </it>and pathogenic mycobacteria in general and will facilitate the development of new tools for improved diagnostics and molecular epidemiology.</p

Reversible vancomycin susceptibility within emerging ST1421 Enterococcus faecium strains is associated with rearranged vanA-gene clusters and increased vanA plasmid copy number

Vancomycin variable enterococci (VVE) are van-positive enterococci with a vancomycin-susceptible phenotype (VVE-S) that can convert to a resistant phenotype (VVE-R) and be selected for during vancomycin exposure. VVE-R outbreaks have been reported in Canada and Scandinavian countries. The aim of this study was to examine the presence of VVE in whole genome sequenced (WGS) Australian bacteremia Enterococcus faecium (Efm) isolates collected through the Australian Group on Antimicrobial resistance (AGAR) network. Eight potential VVEAus isolates, all identified as Efm ST1421, were selected based on the presence of vanA and a vancomycin-susceptible phenotype. During vancomycin selection, two potential VVE-S harboring intact vanHAX genes, but lacking the prototypic vanRS and vanZ genes, reverted to a resistant phenotype (VVEAus-R). Spontaneous VVEAus-R reversion occurred at a frequency of 4-6 × 10−8 resistant colonies per parent cell in vitro after 48 h and led to high-level vancomycin and teicoplanin resistance. The S to R reversion was associated with a 44-bp deletion in the vanHAX promoter region and an increased vanA plasmid copy number. The deletion in the vanHAX promoter region enables an alternative constitutive promoter for the expression of vanHAX. Acquisition of vancomycin resistance was associated with a low fitness cost compared with the corresponding VVEAus-S isolate. The relative proportion of VVEAus-R vs. VVEAus-S decreased over time in serial passages without vancomycin selection. Efm ST1421 is one of the predominant VanA-Efm multilocus sequence types found across most regions of Australia, and has also been associated with a major prolonged VVE outbreak in Danish hospitals

In silico serotyping of E. coli from short read data identifies limited novel O-loci but extensive diversity of O:H serotype combinations within and between pathogenic lineages.

The lipopolysaccharide (O) and flagellar (H) surface antigens of Escherichia coli are targets for serotyping that have traditionally been used to identify pathogenic lineages. These surface antigens are important for the survival of E. coli within mammalian hosts. However, traditional serotyping has several limitations, and public health reference laboratories are increasingly moving towards whole genome sequencing (WGS) to characterize bacterial isolates. Here we present a method to rapidly and accurately serotype E. coli isolates from raw, short read WGS data. Our approach bypasses the need for de novo genome assembly by directly screening WGS reads against a curated database of alleles linked to known and novel E. coli O-groups and H-types (the EcOH database) using the software package srst2. We validated the approach by comparing in silico results for 197 enteropathogenic E. coli isolates with those obtained by serological phenotyping in an independent laboratory. We then demonstrated the utility of our method to characterize isolates in public health and clinical settings, and to explore the genetic diversity of >1500 E. coli genomes from multiple sources. Importantly, we showed that transfer of O- and H-antigen loci between E. coli chromosomal backbones is common, with little evidence of constraints by host or pathotype, suggesting that E. coli 'strain space' may be virtually unlimited, even within specific pathotypes. Our findings show that serotyping is most useful when used in combination with strain genotyping to characterize microevolution events within an inferred population structure

Burkholderia lata Infections from Intrinsically Contaminated Chlorhexidine Mouthwash, Australia, 2016

"Emerging Infectious Diseases is an open access journal in the public domain"Burkholderia lata was isolated from 8 intensive care patients at 2 tertiary hospitals in Australia. Whole-genome sequencing demonstrated that clinical and environmental isolates originated from a batch of contaminated commercial chlorhexidine mouthwash. Genomic analysis identified efflux pump–encoding genes as potential facilitators of bacterial persistence within this biocide

Association of Brain Age, Lesion Volume, and Functional Outcome in Patients With Stroke

BACKGROUND AND OBJECTIVES: Functional outcomes after stroke are strongly related to focal injury measures. However, the role of global brain health is less clear. In this study, we examined the impact of brain age, a measure of neurobiological aging derived from whole-brain structural neuroimaging, on poststroke outcomes, with a focus on sensorimotor performance. We hypothesized that more lesion damage would result in older brain age, which would in turn be associated with poorer outcomes. Related, we expected that brain age would mediate the relationship between lesion damage and outcomes. Finally, we hypothesized that structural brain resilience, which we define in the context of stroke as younger brain age given matched lesion damage, would differentiate people with good vs poor outcomes. METHODS: We conducted a cross-sectional observational study using a multisite dataset of 3-dimensional brain structural MRIs and clinical measures from the ENIGMA Stroke Recovery. Brain age was calculated from 77 neuroanatomical features using a ridge regression model trained and validated on 4,314 healthy controls. We performed a 3-step mediation analysis with robust mixed-effects linear regression models to examine relationships between brain age, lesion damage, and stroke outcomes. We used propensity score matching and logistic regression to examine whether brain resilience predicts good vs poor outcomes in patients with matched lesion damage. RESULTS: We examined 963 patients across 38 cohorts. Greater lesion damage was associated with older brain age (β = 0.21; 95% CI 0.04-0.38, DISCUSSION: We provide evidence that younger brain age is associated with superior poststroke outcomes and modifies the impact of focal damage. The inclusion of imaging-based assessments of brain age and brain resilience may improve the prediction of poststroke outcomes compared with focal injury measures alone, opening new possibilities for potential therapeutic targets

Large tandem chromosome expansions facilitate niche adaptation during persistent infection with drug-resistant Staphylococcus aureus

<p>Fully assembled, closed, annotated genome sequence for S. aureus solate JKD6229</p

S. aureus JKD6210 plasmid sequence

<p>Complete plasmid sequence for S. aureus JKD6210 as published in <em>Microbial Genomics</em> in the following article: Large tandem chromosome expansions facilitate niche adaptation during persistent infection with drug-resistant <em>Staphylococcus aureus</em> [DOI: 10.1099/mgen.0.000026].</p

S. aureus JKD6210 - annotated genome

<p>Completed genome sequence and annotation for S. aureus isolate JKD6210 as published in <em>Microbial Genomics</em> in: Large tandem chromosome expansions facilitate niche adaptation during persistent infection with drug-resistant <em>Staphylococcus aureus</em> [DOI: 10.1099/mgen.0.000026].</p

Supplmentary Table S1

List of publicly available Staphylococcus epidermidis genomes used in this stud

Optical map Staphylococcus aureus JKD6210

<p>optical map image</p