Abstract
Background
Urinary tract infections (UTIs) are a frequent cause for visits to primary care providers. In alignment globally, uropathogenic Escherichia coli (UPEC) are the main aetiological ...agent for UTIs in Norfolk and are increasingly difficult to treat due to multi-drug resistance.
Objectives
We set out to identify which clonal groups and resistance genes are disseminating in the community and hospitals in Norfolk, the first study of its kind for UPEC in this region.
Methods
We collected 199 clinical E. coli isolates causing UTIs in the community and hospital from the Clinical Microbiology laboratory at Norfolk and Norwich University Hospital between August 2021 and January 2022. These were whole-genome sequenced using the Illumina and MinION platforms for in silico MLST and antibiotic resistance determinant detection.
Results
The isolates were composed of 70 STs; 8 lineages represented 56.7% of this population: ST73, ST12, ST69, ST131, ST404, ST95, ST127 and ST1193. Importantly, primary UTI screening deemed 6.5% of isolates to be multidrug resistant (MDR), with high rates of resistance to ampicillin (52.1%) and trimethoprim (36.2%) in hospitals. Of concern is the probable clonal expansion of MDR groups ST131 and ST1193 in hospitals and community settings with chromosomally encoded blaCTX-M-15, blaOXA-1 and aac(6′)-Ib-cr5.
Conclusions
The burden of reported UTIs in Norfolk is largely caused by non-MDR isolates and mirrors similar UPEC studies nationally and internationally. Continually monitoring samples with consideration of sources will help reduce burden of disease.
In addition to nucleotide variation, many bacteria also undergo changes at a much larger scale via rearrangement of their genome structure (GS) around long repeat sequences. These rearrangements ...result in genome fragments shifting position and/or orientation in the genome without necessarily affecting the underlying nucleotide sequence. To date, scalable techniques have not been applied to GS identification, so it remains unclear how extensive this variation is and the extent of its impact upon gene expression. However, the emergence of multiplexed, long‐read sequencing overcomes the scale problem, as reads of several thousand bases are routinely produced that can span long repeat sequences to identify the flanking chromosomal DNA, allowing GS identification. Genome rearrangements were generated in Salmonella enterica serovar Typhi through long‐term culture at ambient temperature. Colonies with rearrangements were identified via long‐range PCR and subjected to long‐read nanopore sequencing to confirm genome variation. Four rearrangements were investigated for differential gene expression using transcriptomics. All isolates with changes in genome arrangement relative to the parent strain were accompanied by changes in gene expression. Rearrangements with similar fragment movements demonstrated similar changes in gene expression. The most extreme rearrangement caused a large imbalance between the origin and terminus of replication and was associated with differential gene expression as a factor of distance moved toward or away from the origin of replication. Genome structure variation may provide a mechanism through which bacteria can quickly adapt to new environments and warrants routine assessment alongside traditional nucleotide‐level measures of variation.
Abstract
Alkaline mafic magmas forming intra-plate oceanic islands are believed to be strongly enriched in CO
2
due to low-degree partial melting of enriched mantle sources. However, until now, such ...CO
2
enhancement has not been verified by measuring CO
2
degassing during a subaerial eruption. Here, we provide evidence of highly CO
2
-rich gas emissions during the 86-day 2021 Tajogaite eruption of Cumbre Vieja volcano on La Palma Island, in the Canary archipelago. Our results reveal sustained high plume CO
2
/SO
2
ratios, which, when combined with SO
2
fluxes, melt inclusion volatile contents and magma production rates at explosive and effusive vents, imply a magmatic CO
2
content of 4.5 ± 1.5 wt%. The amount of CO
2
released during the 2021 eruptive activity was 28 ± 14 Mt CO
2
. Extrapolating to the volume of alkaline mafic magmas forming La Palma alone (estimated as 4000 km
3
erupted over 11 Ma), we infer a maximum CO
2
emission into the ocean and atmosphere of 10
16
moles of CO
2
, equivalent to 20% of the eruptive CO
2
emissions from a large igneous province eruption, suggesting that the formation of the Canary volcanic archipelago produced a CO
2
emission of similar magnitude as a large igneous province.
Antimicrobial-resistance (AMR) genes can be transferred between microbial cells via horizontal gene transfer (HGT), which involves mobile and integrative elements such as plasmids, bacteriophages, ...transposons, integrons and pathogenicity islands. Bacteriophages are found in abundance in the microbial world, but their role in virulence and AMR has not fully been elucidated in the
. With short-read sequencing paving the way to systematic high-throughput AMR gene detection, long-read sequencing technologies now enable us to establish how such genes are structurally connected into meaningful genomic units, raising questions about how they might cooperate to achieve their biological function. Here, we describe a novel ~98 kbp circular P1-bacteriophage-like plasmid termed ph681355 isolated from a clinical
serovar Typhi isolate. It carries
, an IncY plasmid replicon (
gene) and the IS
mobile element and is, to our knowledge, the first reported P1-bacteriophage-like plasmid (phage-plasmid) in
.
Typhi. We compared ph681355 to two previously described phage-plasmids, pSJ46 from
.
serovar Indiana and pMCR-1-P3 from
, and found high nucleotide similarity across the backbone. However, we saw low ph681355 backbone similarity to plasmid p60006 associated with the extensively drug-resistant
.
Typhi outbreak isolate in Pakistan, providing evidence of an alternative route for
transmission. Our discovery highlights the importance of utilizing long-read sequencing in interrogating bacterial genomic architecture to fully understand AMR mechanisms and their clinical relevance. It also raises questions regarding how widespread bacteriophage-mediated HGT might be, suggesting that the resulting genomic plasticity might be higher than previously thought.
Yersinia pestis is the causative agent of plague, a rapidly fatal infectious disease that has not been eradicated worldwide. The capsular Caf1 protein of Y. pestis is a protective antigen under ...development as a recombinant vaccine. However, little is known about the specificity of human T-cell responses for Caf1. We characterized CD4 T-cell epitopes of Caf1 in "humanized" HLA-DR1 transgenic mice lacking endogenous major histocompatibility complex class II molecules. Mice were immunized with Caf1 or each of a complete set of overlapping synthetic peptides, and CD4 T-cell immunity was measured with respect to proliferative and gamma interferon T-cell responses and recognition by a panel of T-cell hybridomas, as well as direct determination of binding affinities of Caf1 peptides to purified HLA-DR molecules. Although a number of DR1-restricted epitopes were identified following Caf1 immunization, the response was biased toward a single immunodominant epitope near the C terminus of Caf1. In addition, potential promiscuous epitopes, including the immunodominant epitope, were identified by their ability to bind multiple common HLA alleles, with implications for the generation of multivalent vaccines against plague for use in humans.
A multicenter, randomized trial involving participants with diabetes and no evident cardiovascular disease at trial entry showed that aspirin led to a lower risk of serious vascular events than ...placebo but also caused a higher risk of major bleeding.
In this trial involving patients with diabetes without evidence of cardiovascular disease, the risk of serious vascular events was similar in those who received n−3 fatty acid supplements and those ...who received placebo.
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