Non-canonical IL-22 receptor signaling remodels the mucosal barrier during fungal immunosurveillance.

Mucosal barrier integrity is vital for homeostasis with commensal organisms while preventing pathogen invasion. We unexpectedly found that fungal-induced immunosurveillance enhances resistance to fungal outgrowth and tissue invasion by remodeling the oral mucosal epithelial barrier in mouse models of adult and neonatal colonization. Epithelial subset expansion and tissue remodeling were dependent on interleukin-22 (IL-22) and signal transducer and activator of transcription 3 (STAT3) signaling, through a non-canonical receptor complex composed of glycoprotein 130 (gp130) coupled with IL-22RA1 and IL-10RB.

Environmental injustice in the air quality for digital platform delivery workers in Bogotá, Colombia, 2021.

Introduction: Air quality is a matter of interest for public health due to its rapid deterioration in low- and middle-income countries and the effects of polluted air on the health of populations.

Objective: To explore the air quality conditions in which digital platform delivery workers carry out their work, evaluating the localities of Kennedy and Usaquén in Bogotá, 2021.

Materials And Methods: We developed a mixed parallel convergent study based on four sources of information: 1) Ethnographic observation in five commercial locations of the two localities; 2) Monitoring of PM10 and PM2.

Clinical presentation and microbiological characteristics of community-acquired bacteraemia at a tertiary hospital in Costa Rica.

is a leading agent in community-acquired bacteraemia (CAB) and has been linked to elevated mortality rates and methicillin resistance in Costa Rica. To update and enhance previous data obtained in this country, we analysed the clinical manifestations of 54  CAB cases in a tertiary hospital and delineated the sequence types (STs), virulome, and resistome of the implicated isolates. Clinical information was retrieved from patient files.

Single-cell detection of copy number changes reveals dynamic mechanisms of adaptation to antifungals in Candida albicans.

Genomic copy number changes are associated with antifungal drug resistance and virulence across diverse fungal pathogens, but the rate and dynamics of these genomic changes in the presence of antifungal drugs are unknown. Here we optimized a dual-fluorescent reporter system in the diploid pathogen Candida albicans to quantify haplotype-specific copy number variation (CNV) and loss of heterozygosity (LOH) at the single-cell level with flow cytometry. We followed the frequency and dynamics of CNV and LOH at two distinct genomic locations in the presence and absence of antifungal drugs in vitro and in a murine model of candidiasis.

Step-wise evolution of azole resistance through copy number variation followed by KSR1 loss of heterozygosity in Candida albicans.

Antimicrobial drug resistance poses a global health threat, requiring a deeper understanding of the evolutionary processes that lead to its emergence in pathogens. Complex evolutionary dynamics involve multiple mutations that can result in cooperative or competitive (clonal interference) effects. Candida albicans, a major fungal pathogen, displays high rates of copy number variation (CNV) and loss of heterozygosity (LOH).

Ancestral Diversity in Pharmacogenomics Affects Treatment for Hispanic/Latine Populations With Inflammatory Bowel Disease.

Background And Aims: The prevalence of inflammatory bowel disease among Hispanic/Latine communities is increasing. Pharmacogenomic studies reveal genetic markers that influence treatment decisions. The aim of our study was to examine the frequency and impact of genetic polymorphisms on thiopurine-associated leukopenia (NUDT15, TPMT) and anti-tumor necrosis factor (TNF) immunogenicity (HLA-DQA1∗05) in a cohort of Hispanic patients of diverse ancestral backgrounds.

Erg251 has complex and pleiotropic effects on sterol composition, azole susceptibility, filamentation, and stress response phenotypes.

Ergosterol is essential for fungal cell membrane integrity and growth, and numerous antifungal drugs target ergosterol. Inactivation or modification of ergosterol biosynthetic genes can lead to changes in antifungal drug susceptibility, filamentation and stress response. Here, we found that the ergosterol biosynthesis gene ERG251 is a hotspot for point mutations during adaptation to antifungal drug stress within two distinct genetic backgrounds of Candida albicans.

A Brg1-Rme1 circuit in hyphal gene regulation.

Major virulence traits include its ability to make hyphae, to produce a biofilm, and to damage host cells. These traits depend upon expression of hypha-associated genes. A gene expression comparison among clinical isolates suggested that transcription factor Rme1 established by previous studies to be a positive regulator of chlamydospore formation, may also be a negative regulator of hypha-associated genes.

Identification of the proteolytic signature in CVB3-infected cells.

Unlabelled: Coxsackievirus B3 (CVB3) encodes proteinases that are essential for processing of the translated viral polyprotein. Viral proteinases also target host proteins to manipulate cellular processes and evade innate antiviral responses to promote replication and infection. While some host protein substrates of the CVB3 3C and 2A cysteine proteinases have been identified, the full repertoire of targets is not known.

Optimization of quenched fluorescent peptide substrates of SARS-CoV-2 3CL main protease (Mpro) from proteomic identification of P6-P6' active site specificity.

SARS-CoV-2 3C-like main protease (3CL) is essential for protein excision from the viral polyprotein. 3CL inhibitor drug development to block SARS-CoV-2 replication focuses on the catalytic non-prime (P) side for specificity and potency, but the importance of the prime (P') side in substrate specificity and for drug development remains underappreciated. We determined the P6-P6' specificity for 3CL from >800 cleavage sites that we identified using Proteomic Identification of Cleavage site Specificity (PICS).

Hyphal Als proteins act as CR3 ligands to promote immune responses against Candida albicans.

Patients with decreased levels of CD18 (β2 integrins) suffer from life-threatening bacterial and fungal infections. CD11b, the α subunit of integrin CR3 (CD11b/CD18, αβ), is essential for mice to fight against systemic Candida albicans infections. Live elongating C.

Erg251 has complex and pleiotropic effects on azole susceptibility, filamentation, and stress response phenotypes.

Ergosterol is essential for fungal cell membrane integrity and growth, and numerous antifungal drugs target ergosterol. Inactivation or modification of ergosterol biosynthetic genes can lead to changes in antifungal drug susceptibility, filamentation and stress response. Here, we found that the ergosterol biosynthesis gene is a hotspot for point mutations during adaptation to antifungal drug stress within two distinct genetic backgrounds of .

The reference strain SC5314 contains a rare, dominant allele of the transcription factor Rob1 that modulates filamentation, biofilm formation, and oral commensalism.

is a commensal fungus that colonizes the human oral cavity and gastrointestinal tract but also causes mucosal as well as invasive disease. The expression of virulence traits in clinical isolates is heterogeneous and the genetic basis of this heterogeneity is of high interest. The reference strain SC5314 is highly invasive and expresses robust filamentation and biofilm formation relative to many other clinical isolates.

Candida albicans stimulates formation of a multi-receptor complex that mediates epithelial cell invasion during oropharyngeal infection.

Fungal invasion of the oral epithelium is central to the pathogenesis of oropharyngeal candidiasis (OPC). Candida albicans invades the oral epithelium by receptor-induced endocytosis but this process is incompletely understood. We found that C.

The reference strain SC5314 contains a rare, dominant allele of the transcription factor Rob1 that modulates biofilm formation and oral commensalism.

Unlabelled: is a diploid human fungal pathogen that displays significant genomic and phenotypic heterogeneity over a range of virulence traits and in the context of a variety of environmental niches. Here, we show that the effects of Rob1 on biofilm and filamentation virulence traits is dependent on both the specific environmental condition and the clinical strain of . The reference strain SC5314 is a heterozygote with two alleles that differ by a single nucleotide polymorphism at position 946 resulting in a serine or proline containing isoform.

Candida albicans Oropharyngeal Infection Is an Exception to Iron-Based Nutritional Immunity.

Candida albicans is a commensal of the human gastrointestinal tract and a common cause of human fungal disease, including mucosal infections, such as oropharyngeal candidiasis and disseminated infections of the bloodstream and deep organs. We directly compared the transcriptional profile of C. albicans during oral infection and disseminated infection of the kidney to identify niche specific features.

Functional Dichotomy for a Hyphal Repressor in Candida albicans.

Nrg1 is a repressor of hypha formation and hypha-associated gene expression in the fungal pathogen Candida albicans. It has been well studied in the genetic background of the type strain SC5314. Here, we tested Nrg1 function in four other diverse clinical isolates through an analysis of Δ/Δ mutants, with SC5314 included as a control.

stimulates the formation of a multi-receptor complex that mediates epithelial cell invasion during oropharyngeal infection.

Unlabelled: Fungal invasion of the oral epithelium is central to the pathogenesis of oropharyngeal candidiasis (OPC). invades the oral epithelium by receptor-induced endocytosis but this process is incompletely understood. We found that infection of oral epithelial cells induces c-Met to form a multi-protein complex with E-cadherin and the epidermal growth factor receptor (EGFR).

Hgc1 Independence of Biofilm Hyphae in Candida albicans.

Biofilm and hypha formation are central to virulence of the fungal pathogen Candida albicans. The G1 cyclin gene is required for hypha formation under diverse and growth conditions. Hgc1 is required for disseminated infection and is a linchpin in the argument that hyphal morphogenesis itself is required for pathogenicity.

oropharyngeal infection is an exception to iron-based nutritional immunity.

is a commensal of the human gastrointestinal tract and one of the most causes of human fungal disease, including mucosal infections such as oropharyngeal candidiasis and disseminated infections of the bloodstream and deep organs. We directly compared the in vivo transcriptional profile of during oral infection and disseminated infection of the kidney to identify niche specific features. Although the expression of a set of environmentally responsive genes were correlated in the two infection sites (Pearson R , 0.

Genetic Characterization in High-Risk Individuals from a Low-Resource City of Peru.

Background: Genetic testing for hereditary cancers is inconsistently applied within the healthcare systems in Latin America. In Peru, the prevalence and spectrum of cancer-predisposing germline variants is thus poorly characterized. Purpose: To determine the spectrum and prevalence of cancer-predisposing germline variants and variants of uncertain significance (VUS) in high-risk individuals located in a Peruvian low-resource setting city.

IL-23 signaling prevents ferroptosis-driven renal immunopathology during candidiasis.

During infection the host relies on pattern-recognition receptors to sense invading fungal pathogens to launch immune defense mechanisms. While fungal recognition and immune effector responses are organ and cell type specific, during disseminated candidiasis myeloid cells exacerbate collateral tissue damage. The β-glucan receptor ephrin type-A 2 receptor (EphA2) is required to initiate mucosal inflammatory responses during oral Candida infection.

Niclosamide-loaded nanoparticles disrupt Candida biofilms and protect mice from mucosal candidiasis.

Candida albicans biofilms are a complex multilayer community of cells that are resistant to almost all classes of antifungal drugs. The bottommost layers of biofilms experience nutrient limitation where C. albicans cells are required to respire.