A spatial transcriptomic atlas of the host response to oropharyngeal candidiasis.

Oropharyngeal candidiasis (OPC) caused by the fungus triggers a robust inflammatory response that rapidly eliminates the bulk of the fungal load in the oral mucosa. While pro-inflammatory responses to OPC have been extensively studied, little is known about the counterbalance of immunity in the infection milieu that mitigates inflammatory damage. We employed 10× Visium Spatial Transcriptomics, a next-generation technology that preserves the spatial integrity of infected tongue tissues, enabling high-resolution mapping of the host microenvironment during infection in a murine OPC model.

A humanized antibody against mucormycosis targets angioinvasion and augments the host immune response.

Mucormycosis is a fungal infection caused by Mucorales fungi that cause severe disease and fatality, especially in immunocompromised individuals. Although vaccines and immunotherapeutics have been successful in combating viral and bacterial infections, approved antifungal immunotherapies are yet to be realized. To address this gap, monoclonal antibodies targeting invasive fungal infections have emerged as a promising approach, particularly for immunocompromised patients who are unlikely to maximally benefit from vaccines.

Candida albicans Recovered From Persistent Candidemia Exhibits Enhanced Virulence Traits.

Candida albicans catheter-related candidemia is largely driven by microbial adhesion and biofilm formation on central venous catheters. Cells that disperse from these biofilms can enter the bloodstream, spread to distant organs, and sustain the cycle of infection. In this study, we investigated the virulence potential of C.

Host immune response against fungal biofilms.

Fungal biofilms are a multilayered community of cells attached to mucosal or abiotic surfaces enclosed in a coating of self-produced extracellular polymeric matrix. The sheer density of cells protected by a polymeric shield not only makes the biofilm impermeable to antimicrobials or immune cells but also hidden from host recognition. Biofilms also serve as a reservoir of drug-resistant persister cells and dispersal cells armored with virulence factors adept at evading the immune system.

Allosteric inhibition of tRNA synthetase Gln4 by N-pyrimidinyl-β-thiophenylacrylamides exerts highly selective antifungal activity.

Candida species are among the most prevalent causes of systemic fungal infections, which account for ∼1.5 million annual fatalities. Here, we build on a compound screen that identified the molecule N-pyrimidinyl-β-thiophenylacrylamide (NP-BTA), which strongly inhibits Candida albicans growth.

Coding Sequence Insertions in Fungal Genomes are Intrinsically Disordered and can Impart Functionally-Important Properties on the Host Protein.

Insertion and deletion mutations (indels) are important mechanisms of generating protein diversity. Indels in coding sequences are under considerable selective pressure to maintain reading frames and to preserve protein function, but once generated, indels provide raw material for the acquisition of new protein properties and functions. We reported recently that coding sequence insertions in the NDU1 protein, a mitochondrial protein involved in the assembly of the NADH:ubiquinone oxidoreductase are imperative for respiration, biofilm formation and pathogenesis.

Antifungal activity of alexidine dihydrochloride in a novel diabetic mouse model of dermatophytosis.

Dermatophytosis is one of the most prevalent fungal infections and a major public health problem worldwide. Recent years have seen a change in the epidemiological patterns of infecting fungi, corresponding to an alarming rise in the prevalence of drug-recalcitrant dermatophyte infections. In patients with diabetes mellitus, dermatophytosis is more severe and recurrent.

A Simple 96-Well Plate-Based Method for Development of Candida Biofilms Under Static Conditions.

We describe a rapid and simple in vitro method for development of Candida biofilms under static growth conditions. This 96-well microtiter-based method measures metabolic activity of sessile cells and can also be easily adapted for antifungal susceptibility testing. The entire procedure takes 2-3 days to complete, reliably quantifies biofilms, and provides reproducible results that are imperative toward the standardization of antifungal susceptibility testing of biofilms.

A Simple Method for Growth of Candida albicans Biofilms Under Continuous Media Flow and for Recovery of Biofilm Dispersed Cells.

Majority of nosocomial infections are associated with biofilms growing on indwelling medical devices. These biofilms are nourished by a continuous flow of body fluids and subjected to shear stress forces. Cells dispersed from C.

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.

Antibodies targeting Als3 and Hyr1 antigens protect neonatal mice from candidiasis.

Pre-term infants in neonatal intensive care units are vulnerable to fungal sepsis. In this patient population, remains the predominant fungal pathogen causing high morbidity and mortality, despite antifungal therapy. Thus, new preventative/therapeutic strategies against neonatal candidiasis are needed.

An evolutionarily diverged mitochondrial protein controls biofilm growth and virulence in Candida albicans.

A forward genetic screening approach identified orf19.2500 as a gene controlling Candida albicans biofilm dispersal and biofilm detachment. Three-dimensional (3D) protein modeling and bioinformatics revealed that orf19.

GRP78 and Integrins Play Different Roles in Host Cell Invasion during Mucormycosis.

Mucormycosis, caused by species, is a life-threatening fungal infection that occurs in patients immunocompromised by diabetic ketoacidosis (DKA), cytotoxic chemotherapy, immunosuppressive therapy, hematologic malignancies, or severe trauma. Inhaled spores cause pulmonary infections in patients with hematologic malignancies, while patients with DKA are much more prone to rhinoorbital/cerebral mucormycosis. Here, we show that interacts with glucose-regulated protein 78 (GRP78) on nasal epithelial cells via its spore coat protein CotH3 to invade and damage the nasal epithelial cells.

Monoclonal IgM Antibodies Targeting Hyr1 Provide Cross-Kingdom Protection Against Gram-Negative Bacteria.

Recent years have seen an unprecedented rise in the incidence of multidrug-resistant (MDR) Gram-negative bacteria (GNBs) such as and species. In view of the shortage of novel drugs in the pipeline, alternative strategies to prevent, and treat infections by GNBs are urgently needed. Previously, we have reported that the hypha-regulated protein Hyr1 shares striking three-dimensional structural homology with cell surface proteins of .

Candida auris Biofilm Colonization on Skin Niche Conditions.

, an emerging multidrug-resistant yeast, has recently been associated with outbreaks of invasive infections in health care facilities worldwide. Its success as a nosocomial pathogen lies in its capability to sustain for prolonged periods in the intensive care unit (ICU), adeptly colonize skin, and spread among patients. Little is known of the mechanism behind the predilection of for skin or the extent of its resilience on it.

A Study of Antifungal Susceptibility Patterns of Dermatophytic Fungi at a Tertiary Care Center in Western India.

Background: Recent years have seen an alarming rise in the prevalence of recalcitrant and relapsing dermatophyte infections in India associated with lack of clinical response to standard antifungal regimens.

Aims And Objectives: A study was undertaken to identify the antifungal susceptibility patterns of dermatophyte species isolated from lesions of dermatophytoses in patients examined at our center.

Materials And Methods: A total of 85 patients with clinically diagnosed dermatophytoses were subjected to skin scrapings for potassium hydroxide mount (microscopic examination) and culture using Sabouraud's agar medium containing chloramphenicol and cycloheximide (incubated at 30°C).

The NDV-3A vaccine protects mice from multidrug resistant Candida auris infection.

Candida auris is an emerging, multi-drug resistant, health care-associated fungal pathogen. Its predominant prevalence in hospitals and nursing homes indicates its ability to adhere to and colonize the skin, or persist in an environment outside the host-a trait unique from other Candida species. Besides being associated globally with life-threatening disseminated infections, C.

Anti-CotH3 antibodies protect mice from mucormycosis by prevention of invasion and augmenting opsonophagocytosis.

Mucorales are fungal pathogens that cause mucormycosis, a lethal angioinvasive disease. Previously, we demonstrated that , the most common cause of mucormycosis, invades endothelial cells by binding of its CotH proteins to the host receptor GRP78. Loss of CotH3 renders the fungus noninvasive and attenuates virulence in mice.

Candida albicans biofilm growth and dispersal: contributions to pathogenesis.

The fungal species Candida albicans is most frequently associated with biofilm formation in immune-compromised and medically compromised patients, and it is now firmly established that biofilm formation represents a major virulence factor during candidiasis. A growing body of evidence has demonstrated that C. albicans biofilm development is a highly regulated and coordinated process, where adhesive interactions, morphogenetic conversions, and consortial behavior play significant roles.

NDV-3A vaccination prevents C. albicans colonization of jugular vein catheters in mice.

NDV-3A, a novel fungal vaccine undergoing clinical trials, contains a recombinant version of the Candida albicans rAls3 N-terminus protein (rAls3p-N) in aluminum hydroxide. In a Phase 1b/2a clinical trial, NDV-3A protected women from recurrent vulvovaginal candidiasis. Here, we reveal that active immunization in mice with NDV-3A induces high titers of anti-rAls3p-N antibodies that interfere with C.

Metabolic Profiling of Candida auris, a Newly-Emerging Multi-Drug Resistant Candida Species, by GC-MS.

, a newly-emerging species, is a serious global health threat due to its multi-drug resistant pattern, difficulty to diagnose, and the high mortality associated with its invasive and bloodstream infections. Unlike and which can form true hyphae, grows as yeast or pseudohyphae and is capable of developing biofilms. The reasons for the inability of to form true hyphae are currently unknown.

Alexidine Dihydrochloride Has Broad-Spectrum Activities against Diverse Fungal Pathogens.

Invasive fungal infections due to , , and constitute a substantial threat to hospitalized immunocompromised patients. Further, the presence of drug-recalcitrant biofilms on medical devices and emergence of drug-resistant fungi, such as , introduce treatment challenges with current antifungal drugs. Worse, currently there is no approved drug capable of obviating preformed biofilms, which increase the chance of infection relapses.

Dispersed Cells Are Developmentally Distinct from Biofilm and Planktonic Cells.

surface-attached biofilms such as those formed on intravenous catheters with direct access to the bloodstream often serve as a nidus for continuous release of cells capable of initiating new infectious foci. We previously reported that cells dispersed from a biofilm are yeast cells that originate from the top-most hyphal layers of the biofilm. Compared to their planktonic counterparts, these biofilm dispersal yeast cells displayed enhanced virulence-associated characteristics and drug resistance.