Draft genome of a human-derived that caused spontaneous disseminated infection in a mouse.

We present the draft genome of a novel human-derived strain isolated from a healthy control human microbiota that, when put into a mouse, spontaneously disseminated from the gut to the kidneys.

Plant phenolics inhibit focal adhesion kinase and suppress host cell invasion by uropathogenic .

Traditional folk treatments for the prevention and management of urinary tract infections (UTIs) and other infectious diseases often include plants and plant extracts that are rich in phenolic compounds. These have been ascribed a variety of activities, including inhibition of bacterial interactions with host cells. Here, we tested a panel of four well-studied phenolic compounds-caffeic acid phenethyl ester (CAPE), resveratrol, catechin, and epigallocatechin gallate-for the effects on host cell adherence and invasion by uropathogenic (UPEC).

Bacterial diversity and chemical ecology of natural product-producing bacteria from Great Salt Lake sediment.

Great Salt Lake (GSL), located northwest of Salt Lake City, UT, is the largest terminal lake in the USA. While the average salinity of seawater is ~3.3%, the salinity in GSL ranges between 5% and 28%.

Resistance Gene Association and Inference Network (ReGAIN): A Bioinformatics Pipeline for Assessing Probabilistic Co-Occurrence Between Resistance Genes in Bacterial Pathogens.

The rampant rise of multidrug resistant (MDR) bacterial pathogens poses a severe health threat, necessitating innovative tools to unravel the complex genetic underpinnings of antimicrobial resistance. Despite significant strides in developing genomic tools for detecting resistance genes, a gap remains in analyzing organism-specific patterns of resistance gene co-occurrence. Addressing this deficiency, we developed the Resistance Gene Association and Inference Network (ReGAIN), a novel web-based and command line genomic platform that uses Bayesian network structure learning to identify and map resistance gene networks in bacterial pathogens.

Plant Phenolics Inhibit Focal Adhesion Kinase and Suppress Host Cell Invasion by Uropathogenic .

Traditional folk treatments for the prevention and management of urinary tract infections (UTIs) and other infectious diseases often include plants and plant extracts that are rich in phenolic and polyphenolic compounds. These have been ascribed a variety of activities, including inhibition of bacterial interactions with host cells. Here we tested a panel of four well-studied phenolic compounds - caffeic acid phenethyl ester (CAPE), resveratrol, catechin, and epigallocatechin gallate - for effects on host cell adherence and invasion by uropathogenic (UPEC).

Bacterial Diversity and Chemical Ecology of Natural Product-Producing Bacteria from Great Salt Lake Sediment.

Great Salt Lake (GSL), located northwest of Salt Lake City, UT, is the largest terminal lake in the United States. While the average salinity of seawater is ~3.3%, the salinity in GSL ranges between 5-28%.

Common pili promote the fitness and virulence of a hybrid aEPEC/ExPEC strain within diverse host environments.

Pathogenic subsets of include diarrheagenic (DEC) strains that cause disease within the gut and extraintestinal pathogenic (ExPEC) strains that are linked with urinary tract infections, bacteremia, and other infections outside of intestinal tract. Among DEC strains is an emergent pathotype known as atypical enteropathogenic (aEPEC), which can cause severe diarrhea. Recent sequencing efforts revealed that some strains possess genetic features that are characteristic of both DEC and ExPEC isolates.

Ucl fimbriae regulation and glycan receptor specificity contribute to gut colonisation by extra-intestinal pathogenic Escherichia coli.

Extra-intestinal pathogenic Escherichia coli (ExPEC) belong to a critical priority group of antibiotic resistant pathogens. ExPEC establish gut reservoirs that seed infection of the urinary tract and bloodstream, but the mechanisms of gut colonisation remain to be properly understood. Ucl fimbriae are attachment organelles that facilitate ExPEC adherence.

The Cdkn2a gene product p19 alternative reading frame (p19ARF) is a critical regulator of IFNβ-mediated Lyme arthritis.

Type I interferon (IFN) has been identified in patients with Lyme disease, and its abundant expression in joint tissues of C3H mice precedes development of Lyme arthritis. Forward genetics using C3H mice with severe Lyme arthritis and C57BL/6 (B6) mice with mild Lyme arthritis identified the Borrelia burgdorferi arthritis-associated locus 1 (Bbaa1) on chromosome 4 (Chr4) as a regulator of B. burgdorferi-induced IFNβ expression and Lyme arthritis severity.

A tRNA modifying enzyme as a tunable regulatory nexus for bacterial stress responses and virulence.

Post-transcriptional modifications can impact the stability and functionality of many different classes of RNA molecules and are an especially important aspect of tRNA regulation. It is hypothesized that cells can orchestrate rapid responses to changing environmental conditions by adjusting the specific types and levels of tRNA modifications. We uncovered strong evidence in support of this tRNA global regulation hypothesis by examining effects of the well-conserved tRNA modifying enzyme MiaA in extraintestinal pathogenic Escherichia coli (ExPEC), a major cause of urinary tract and bloodstream infections.

Lysosomal iron recycling in mouse macrophages is dependent upon both LcytB and Steap3 reductases.

Iron that is stored in macrophages as ferritin can be made bioavailable by degrading ferritin in the lysosome and releasing iron back into the cytosol. Iron stored in ferritin is found as Fe3+ and must be reduced to Fe2+ before it can be exported from the lysosome. Here we report that the lysosomal reductase Cyb561a3 (LcytB) and the endosomal reductase six-transmembrane epithelial antigen of prostate 3 (Steap3) act as lysosomal ferrireductases in the mouse macrophage cell line RAW264.

Bile Salts Regulate Zinc Uptake and Capsule Synthesis in a Mastitis-Associated Extraintestinal Pathogenic Escherichia coli Strain.

Extraintestinal pathogenic Escherichia coli (ExPEC) strains are major causes of urinary and bloodstream infections. ExPEC reservoirs are not completely understood. Some mastitis-associated E.

Mucosal-associated invariant T (MAIT) cells mediate protective host responses in sepsis.

Sepsis is a systemic inflammatory response to infection and a leading cause of death. Mucosal-associated invariant T (MAIT) cells are innate-like T cells enriched in mucosal tissues that recognize bacterial ligands. We investigated MAIT cells during clinical and experimental sepsis, and their contribution to host responses.

Clinical and molecular epidemiology of invasive Staphylococcus aureus infection in Utah children; continued dominance of MSSA over MRSA.

Background: Invasive Staphylococcus aureus infections are a common cause of morbidity and mortality in children. In the early 2000's the proportion of infections due the methicillin-resistant S. aureus (MRSA) increased rapidly.

Commensal Strains of Neisseria Use DNA to Poison Their Pathogenic Rivals.

Commensal bacteria can interfere with colonization of the host by infiltrating pathogens. In this issue of Cell Host & Microbe, Kim et al. (2019) describe an intriguing mechanism of colonization resistance driven by the mismatching of methylation patterns following uptake of commensal-derived DNA by pathogenic strains of Neisseria.

Population dynamics of an Escherichia coli ST131 lineage during recurrent urinary tract infection.

Recurrent urinary tract infections (rUTIs) are extremely common, with ~ 25% of all women experiencing a recurrence within 1 year of their original infection. Escherichia coli ST131 is a globally dominant multidrug resistant clone associated with high rates of rUTI. Here, we show the dynamics of an ST131 population over a 5-year period from one elderly woman with rUTI since the 1970s.

Context-Dependent Requirements for FimH and Other Canonical Virulence Factors in Gut Colonization by Extraintestinal Pathogenic Escherichia coli.

Extraintestinal pathogenic (ExPEC) acts as a commensal within the mammalian gut but can induce pathology upon dissemination to other host environments such as the urinary tract and bloodstream. ExPEC genomes are likely shaped by evolutionary forces encountered within the gut, where the bacteria spend much of their time, provoking the question of how their extraintestinal virulence traits arose. The principle of coincidental evolution, in which a gene that evolved in one niche happens to be advantageous in another, has been used to argue that ExPEC virulence factors originated in response to selective pressures within the gut ecosystem.

High-throughput identification and rational design of synergistic small-molecule pairs for combating and bypassing antibiotic resistance.

Antibiotic-resistant infections kill approximately 23,000 people and cost $20,000,000,000 each year in the United States alone despite the widespread use of small-molecule antimicrobial combination therapy. Antibiotic combinations typically have an additive effect: the efficacy of the combination matches the sum of the efficacies of each antibiotic when used alone. Small molecules can also act synergistically when the efficacy of the combination is greater than the additive efficacy.

The Rhomboid Protease GlpG Promotes the Persistence of Extraintestinal Pathogenic Escherichia coli within the Gut.

Extraintestinal pathogenic (ExPEC) strains are typically benign within the mammalian gut but can disperse to extraintestinal sites to cause diseases like urinary tract infections and sepsis. As occupation of the intestinal tract is often a prerequisite for ExPEC-mediated pathogenesis, we set out to understand how ExPEC colonizes this niche. A screen using transposon sequencing (Tn-seq) was performed to search for genes within ExPEC isolate F11 that are important for growth in intestinal mucus, which is thought to be a major source of nutrients for in the gut.

Dual colorimetric and fluorogenic probes for visualizing tyrosine phosphatase activity.

Two resorufin-based substrates for protein tyrosine phosphatase (PTP) activity have been synthesized. These substrates provide sensitive fluorogenic readouts of PTP activity in vitro and in living cells at both acidic and neutral pH. In addition, the presence of the pathogenic bacteria Staphylococcus aureus was detected visually using a colorimetric readout.

Escherichia coli O78 isolated from septicemic lambs shows high pathogenicity in a zebrafish model.

The pathogenicity of Escherichia coli O78 strain K46, originally isolated from an outbreak of septicemia in neonatal lambs, was investigated in zebrafish embryo and murine models of infection. Its biofilm potential, cellulose production, and the expression of type 1 pili and curli fimbriae were measured by in vitro assays. The strain was highly pathogenic in the zebrafish embryo model of infection, where it killed all embryos within 24 h post inoculation (hpi) at doses as low as 1000 colony forming units.

Repeated Treatments with Chitosan in Combination with Antibiotics Completely Eradicate Uropathogenic Escherichia coli From Infected Mouse Urinary Bladders.

Uropathogenic Escherichia coli (UPEC), the primary causative agents of urinary tract infections, colonize and invade the epithelial cells of the bladder urothelium. Infection of immature urothelial cells can result in the formation of persistent intracellular reservoirs that are refractory to antibiotic treatments. Previously, we defined a novel therapeutic strategy that used the bladder cell exfoliant chitosan to deplete UPEC reservoirs.

Invasion of Host Cells and Tissues by Uropathogenic Bacteria.

Within the mammalian urinary tract uropathogenic bacteria face many challenges, including the shearing flow of urine, numerous antibacterial molecules, the bactericidal effects of phagocytes, and a scarcity of nutrients. These problems may be circumvented in part by the ability of uropathogenic Escherichia coli and several other uropathogens to invade the epithelial cells that line the urinary tract. By entering host cells, uropathogens can gain access to additional nutrients and protection from both host defenses and antibiotic treatments.

Similarly Lethal Strains of Extraintestinal Pathogenic Escherichia coli Trigger Markedly Diverse Host Responses in a Zebrafish Model of Sepsis.

In individuals with sepsis, the infecting microbes are commonly viewed as generic inducers of inflammation while the host background is considered the primary variable affecting disease progression and outcome. To study the effects of bacterial strain differences on the maladaptive immune responses that are induced during sepsis, we employed a novel zebrafish embryo infection model using extraintestinal pathogenic Escherichia coli (ExPEC) isolates. These genetically diverse pathogens are a leading cause of sepsis and are becoming increasingly dangerous because of the rise of multidrug-resistant strains.