The proteomic response of to amphotericin B (AmB) reveals the involvement of the RTA-like protein RtaA in AmB resistance.

The polyene antimycotic amphotericin B (AmB) and its liposomal formulation AmBisome belong to the treatment options of invasive aspergillosis caused by . Increasing resistance to AmB in clinical isolates of species is a growing concern, but mechanisms of AmB resistance remain unclear. In this study, we conducted a proteomic analysis of exposed to sublethal concentrations of AmB and AmBisome.

Optimized psilocybin production in tryptophan catabolism-repressed fungi.

The high therapeutic potential of psilocybin, a prodrug of the psychotropic psilocin, holds great promise for the treatment of mental disorders such as therapy-refractory depression, alcohol use disorder and anorexia nervosa. Psilocybin has been designated a 'Breakthrough Therapy' by the US Food and Drug Administration, and therefore a sustainable production process must be established to meet future market demands. Here, we present the development of an in vivo psilocybin production chassis based on repression of l-tryptophan catabolism.

RNA:DNA triplexes: a mechanism for epigenetic communication between hosts and microbes?

Molecular communication between host and microbe is mediated by the transfer of many different classes of macromolecules. Recently, the trafficking of RNA molecules between organisms has gained prominence as an efficient way to manipulate gene expression via RNA interference (RNAi). Here, we posit a new epigenetic control mechanism based on triple helix (triplex) structures comprising nucleic acids from both host and microbe.

A global survey of host, aquatic, and soil microbiomes reveals shared abundance and genomic features between bacterial and fungal generalists.

Environmental change, coupled with alteration in human lifestyles, is profoundly impacting the microbial communities critical to the health of the Earth and its inhabitants. To identify bacteria and fungi that are resistant and susceptible to habitat change, we analyze thousands of genera detected in 1,580 host, soil, and aquatic samples. This large-scale analysis identifies 48 bacterial and 4 fungal genera that are abundant across the three biomes, demonstrating fitness in diverse environmental conditions.

Disruption of the RNA interference machinery alters the conidial transcriptome.

The RNA interference (RNAi) pathway has evolved numerous functionalities in eukaryotes, with many on display in Kingdom Fungi. RNAi can regulate gene expression, facilitate drug resistance, or even be altogether lost to improve growth potential in some fungal pathogens. In the WHO fungal priority pathogen, , the RNAi system is known to be intact and functional.

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.

Aspergillus fumigatus pan-genome analysis identifies genetic variants associated with human infection.

Aspergillus fumigatus is an environmental saprobe and opportunistic human fungal pathogen. Despite an estimated annual occurrence of more than 300,000 cases of invasive disease worldwide, a comprehensive survey of the genomic diversity present in A. fumigatus-including the relationship between clinical and environmental isolates and how this genetic diversity contributes to virulence and antifungal drug resistance-has been lacking.

Effects of Agricultural Fungicide Use on Aspergillus fumigatus Abundance, Antifungal Susceptibility, and Population Structure.

Antibiotic resistance is an increasing threat to human health. In the case of , which is both an environmental saprobe and an opportunistic human fungal pathogen, resistance is suggested to arise from fungicide use in agriculture, as the azoles used for plant protection share the same molecular target as the frontline antifungals used clinically. However, limiting azole fungicide use on crop fields to preserve their activity for clinical use could threaten the global food supply via a reduction in yield.

Low rate of azole resistance in cases of avian aspergillosis in Germany.

Aspergillosis is the most common fungal disease of the avian respiratory tract. Due to delayed diagnosis and treatment failure, the outcome of these infections is often poor. We investigate 159 cases of avian aspergillosis among captive birds in Germany to define clinical features as well as the frequency of in vitro triazole resistance.

Candida auris in Germany and Previous Exposure to Foreign Healthcare.

The emerging yeast Candida auris has disseminated worldwide. We report on 7 cases identified in Germany during 2015-2017. In 6 of these cases, C.

Comparative Genomics of Serial Isolates and the Rapid Acquisition of Echinocandin Resistance during Therapy.

The opportunistic pathogen shows a concerning increase in drug resistance. Here, we present the analysis of two serial bloodstream isolates, obtained 12 days apart. Both isolates show pan-azole resistance and echinocandin resistance was acquired during the sampling interval.

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.

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.

Strengths and Limitations of Model Systems for the Study of Urinary Tract Infections and Related Pathologies.

Urinary tract infections (UTIs) are some of the most common bacterial infections worldwide and are a source of substantial morbidity among otherwise healthy women. UTIs can be caused by a variety of microbes, but the predominant etiologic agent of these infections is uropathogenic Escherichia coli (UPEC). An especially troubling feature of UPEC-associated UTIs is their high rate of recurrence.

Urinary tract infections: current and emerging management strategies.

Acute cystitis is one of the most commonly encountered bacterial infections and is responsible for substantial morbidity and high medical costs in the United States and across the globe. Though generally considered to be self-limiting and easily treated with antibiotics, urinary tract infections (UTIs) are often incompletely resolved by antibiotic therapy and frequently recur. This is in part due to the ability of uropathogenic bacteria to invade, replicate, and persist within host epithelial cells.

The Cpx stress response system potentiates the fitness and virulence of uropathogenic Escherichia coli.

Strains of uropathogenic Escherichia coli (UPEC) are the primary cause of urinary tract infections, representing one of the most widespread and successful groups of pathogens on the planet. To colonize and persist within the urinary tract, UPEC must be able to sense and respond appropriately to environmental stresses, many of which can compromise the bacterial envelope. The Cpx two-component envelope stress response system is comprised of the inner membrane histidine kinase CpxA, the cytosolic response regulator CpxR, and the periplasmic auxiliary factor CpxP.

Ex vivo delivery of GDNF maintains motor function and prevents neuronal loss in a transgenic mouse model of Huntington's disease.

Huntington's disease (HD) is an autosomal dominant disorder caused by expansion of polyglutamine repeats in the huntingtin gene leading to loss of striatal and cortical neurons followed by deficits in cognition and choreic movements. Growth factor delivery to the brain has shown promise in various models of neurodegenerative diseases, including HD, by reducing neuronal death and thus limiting motor impairment. Here we used mouse neural progenitor cells (mNPCs) as growth factor delivery vehicles in the N171-82Q transgenic mouse model of HD.

Human neural progenitor cells over-expressing IGF-1 protect dopamine neurons and restore function in a rat model of Parkinson's disease.

Growth factors such as glial cell line-derived neurotrophic factor (GDNF) have been shown to prevent neurodegeneration and promote regeneration in many animal models of Parkinson's disease (PD). Insulin-like growth factor 1 (IGF-1) is also known to have neuroprotective effects in a number of disease models but has not been extensively studied in models of PD. We produced human neural progenitor cells (hNPC) releasing either GDNF or IGF-1 and transplanted them into a rat model of PD.