Biology subjects

Snesrud, E.

Publications and source records attributed to Snesrud, E..

4 recordsLinked to original sources

bioRxiv2023

Evolution and spread of a persistent P. aeruginosa outbreak clone over decades in a single US hospital.

Whole-genome sequencing is revolutionizing bacterial outbreak investigation but its application to the clinic remains limited. In 2020, prospective and retrospective surveillance detected a Pseudomonas aeruginosa outbreak with 253 isolates collected from 82 patients in 26 wards of a hospital. Its origin was dated to the late 90s, just after the facility opened, and patient-to-patient and environment-to-patient cases of transmission were inferred. Over time, two epidemic subclones evolved in separate hosts and hospital areas, including newly opened wards, and hospital-wide sampling confirmed reservoirs persisted in the plumbing. Pathoadaptive mutations in genes associated with virulence, cell wall biogenesis, and antibiotic resistance were identified. While the latter correlated with the acquisition of phenotypic resistances to 1st (cephalosporin), 2nd (carbapenems) and 3rd (colistin) lines of treatment, maximum parsimony suggested that a truncation in a lipopolysaccharide component coincided with the emergence of a subclone prevalent in long-term infections. Since initial identification, extensive infection control efforts guided by routine, near real-time surveillance have proved successful at slowing transmission.

microbiology↗

bioRxiv2021

TnCentral: A Prokaryotic Transposable Element Database and Web Portal for Transposon Analysis

We describe here the structure and organization of TnCentral (https://tncentral.proteininformationresource.org/). a web resource for prokaryotic transposable elements (TE). TnCentral currently contains ~400 carefully annotated TE, including transposons from the Tn3, Tn7, Tn402 and Tn554 families, compound transposons, integrons and associated insertion sequences (IS). These TE carry passenger genes, including genes conferring resistance to over 25 classes of antibiotics and nine types of heavy metal as well as genes responsible for pathogenesis in plants, toxin/antitoxin gene pairs, transcription factors and genes involved in metabolism. Each TE has its own entry page providing details about its transposition genes, passenger genes, and other sequence features required for transposition as well as a graphical map of all features. TnCentral content can be browsed and queried through text and sequence-based searches with a graphic output. We describe three use cases, which illustrate how the search interface, results tables, and entry pages can be used to explore and compare TEs. TnCentral also includes downloadable software to facilitate user-driven identification, with manual annotation, of certain types of TE in genomic sequences. Through the TnCentral homepage, users can also access TnPedia which provides comprehensive reviews of the major TE families including an extensive general section, and specialised sections with descriptions of insertion sequence and transposon families. TnCentral and TnPedia are intuitive resources that can be used by clinicians and scientists to assess TE diversity in clinical, veterinary and environmental samples. ImportanceThe ability of bacteria to undergo rapid evolution and adapt to changing environmental circumstances drives the public health crisis of multiple antibiotic resistance as well as outbreaks of disease in economically important agricultural crops and animal husbandry. Prokaryotic transposable elements (TE) play a critical role in this. Many carry "passenger genes" (not required for the transposition process) conferring resistance to antibiotics or heavy metals or causing disease in plants and animals. Passenger genes are spread by the normal TE transposition activities, by insertion into plasmids which then spread via conjugation within and across bacterial populations. Thus, an understanding of TE composition and transposition mechanisms is key to developing strategies to combat bacterial pathogenesis. Toward this end, we have developed TnCentral, a bioinformatics resource dedicated to describing and exploring the structural and functional features of prokaryotic TE and whose use is intuitive and accessible to users with or without bioinformatics expertise.

genomics↗

bioRxiv2021

A Panel of Diverse Pseudomonas aeruginosa Clinical Isolates for Research and Development

Pseudomonas aeruginosa is a leading cause of community-acquired and hospital-acquired infections. Successful treatment is hampered by its remarkable ability to rapidly develop resistance to antimicrobial agents, mostly through mutation. In response, the World Health Organization listed carbapenem-resistant P. aeruginosa as a Priority 1 (Critical) pathogen for research and development of new treatments. A key resource in developing effective countermeasures is access to diverse and clinically relevant strains for testing. Herein we describe a panel of 100 diverse P. aeruginosa strains to support this endeavor. Whole genome sequencing was performed on 3,785 P. aeruginosa housed in our repository. Isolates were cultured from clinical samples collected from healthcare facilities around the world between 2003 and 2017. Core-genome multi-locus sequence typing and high-resolution SNP-based phylogenetic analyses were used to select a panel of 100 strains that captured the genetic diversity of this collection. Comprehensive antibiotic susceptibility testing was also performed using 14 clinically relevant antibiotics. This 100-strain diversity panel contained representative strains from 91 different sequence-types, including genetically distinct isolates from major epidemic clones ST-111, ST-235, ST-244, and ST-253. Seventy-one distinct antibiotic susceptibility profiles were identified ranging from pan-sensitive to pan-resistant. Known resistance alleles as well as the most prevalent mutations underlying the antibiotic susceptibilities were characterized for all isolates. This panel provides a diverse and comprehensive set of P. aeruginosa strains for use in developing solutions to antibiotic resistance. The isolates, and all available meta-data including genome sequences, are available to industry, academic institutions, federal and other laboratories at no additional cost. ImportancePseudomonas aeruginosa is one of the most important human pathogens and a leading target in the development of new drugs and therapeutics. This species displays a remarkable level of diversity and any potential therapeutic must contend with this characteristic to ensure it retains efficacy across different strains. To date, only limited panels of P. aeruginosa are available for testing, and none have been designed to capture the genetic diversity of the species. The panel described herein has been designed to address this shortcoming by providing a set of 100 distinct strains that greatly captures the diversity of the species. This panel will be of significant value to research groups working on this important pathogen, both for research purposes and in the development of new diagnostics and countermeasures.

microbiology↗

bioRxiv2018

Chromosomally Encoded mcr-5 in Colistin Non-susceptible Pseudomonas aeruginosa

Whole genome sequencing (WGS) of historical Pseudomonas aeruginosa clinical isolates identified a chromosomal copy of mcr-5 within a Tn3-like transposon in P. aeruginosa MRSN 12280. The isolate was non-susceptible to colistin by broth microdilution and genome analysis revealed no mutations known to confer colistin resistance. To the best of our knowledge this is the first report of mcr in colistin non-susceptible P. aeruginosa.

microbiology↗