Microevolution of Cryptococcus neoformans in high CO converges on mutations isolated from patients with relapsed cryptococcosis.

Cryptococcus neoformans is an environmental fungus that causes an estimated 180,000 deaths annually and transitions from the external environment to the host environment to cause disease. CO concentrations in the atmosphere (0.04%) are dramatically lower than in mammalian tissues (5%).

Cryptococcus neoformans adapts to the host environment through TOR-mediated remodeling of phospholipid asymmetry.

Cryptococcus spp. are environmental fungi that first must adapt to the host environment before they can cause life-threatening meningitis in immunocompromised patients. Host CO concentrations are 100-fold higher than the external environment and strains unable to grow at host CO concentrations are not pathogenic.

Intravital imaging-based genetic screen reveals the transcriptional network governing filamentation during mammalian infection.

is one of the most common human fungal pathogens. pathogenesis is tightly linked to its ability to under a morphogenetic transition from typically budding yeast to filamentous forms of hyphae and pseudohyphae. Filamentous morphogenesis is the most intensively studied virulence traits; however, nearly all of these studies have been based on in vitro induction of filamentation.

Carbon Dioxide Potentiates Flucytosine Susceptibility in Cryptococcus neoformans.

Cryptococcal meningoencephalitis remains a global health threat with limited treatment options. Currently, the most effective treatment regimens are based on a combination therapy of flucytosine with either amphotericin B or fluconazole. Slow but steady progress is being made toward universal access to flucytosine-based therapies.

The RAM signaling pathway links morphology, thermotolerance, and CO tolerance in the global fungal pathogen .

The environmental pathogen claims over 180,000 lives each year. Survival of this basidiomycete at host CO concentrations has only recently been considered an important virulence trait. Through screening gene knockout libraries constructed in a CO-tolerant clinical strain, we found mutations leading to CO sensitivity are enriched in pathways activated by heat stress, including calcineurin, Ras1-Cdc24, cell wall integrity, and egulator of ce2 and orphogenesis (RAM).

Is Required for Cryptococcus neoformans Fitness : Application of Copper-Regulated Gene Expression to Mouse Models of Cryptococcosis.

There is an urgent need for new antifungals to treat cryptococcal meningoencephalitis, a leading cause of mortality in people living with HIV/AIDS. An important aspect of antifungal drug development is the validation of targets to determine whether they are required for the survival of the organism in animal models of disease. In Cryptococcus neoformans, a copper-regulated promoter (pCTR4-2) has been used previously to modulate gene expression .

The granuloma in cryptococcal disease.

Although we have recognized cryptococcosis as a disease entity for well over 100 years, there are many details about its pathogenesis which remain unknown. A major barrier to better understanding is the very broad range of clinical and pathological forms cryptococcal infections can take. One such form has been historically called the cryptococcal granuloma, or the cryptococcoma.

The Ndr/LATS Kinase Cbk1 Regulates a Specific Subset of Ace2 Functions and Suppresses the Hypha-to-Yeast Transition in Candida albicans.

The egulation of ce2 and orphogenesis (RAM) pathway is an important regulatory network in the human fungal pathogen The RAM pathway's two most well-studied components, the NDR/Lats kinase Cbk1 and its putative substrate, the transcription factor Ace2, have a wide range of phenotypes and functions. It is not clear, however, which of these functions are specifically due to the phosphorylation of Ace2 by Cbk1. To address this question, we first compared the transcriptional profiles of and deletion mutants.

RTX Toxins Ambush Immunity's First Cellular Responders.

The repeats-in-toxin (RTX) family represents a unique class of bacterial exoproteins. The first family members described were toxins from Gram-negative bacterial pathogens; however, additional members included exoproteins with diverse functions. Our review focuses on well-characterized RTX family toxins from (LtxA), (LktA), (CyaA), uropathogenic (HlyA), and (ApxIIIA), as well as the studies that have honed in on a single host cell receptor for RTX toxin interactions, the β integrins.

The Extracellular Domain of the β Integrin β Subunit (CD18) Is Sufficient for Escherichia coli Hemolysin and Aggregatibacter actinomycetemcomitans Leukotoxin Cytotoxic Activity.

The hemolysin (HlyA) is a pore-forming exotoxin associated with severe complications of human urinary tract infections. HlyA is the prototype of the repeats-in-toxin (RTX) family, which includes LtxA from , a periodontal pathogen. The existence and requirement for a host cell receptor for these toxins are controversial.

Live Attenuated Borrelia burgdorferi Targeted Mutants in an Infectious Strain Background Protect Mice from Challenge Infection.

Borrelia burgdorferi, B. garinii, and B. afzelii are all agents of Lyme disease in different geographic locations.

Intravital Imaging of Vascular Transmigration by the Lyme Spirochete: Requirement for the Integrin Binding Residues of the B. burgdorferi P66 Protein.

Vascular extravasation, a key step in systemic infection by hematogenous microbial pathogens, is poorly understood, but has been postulated to encompass features similar to vascular transmigration by leukocytes. The Lyme disease spirochete can cause a variety of clinical manifestations, including arthritis, upon hematogenous dissemination. This pathogen encodes numerous surface adhesive proteins (adhesins) that may promote extravasation, but none have yet been implicated in this process.

Hemolysin of uropathogenic Escherichia coli: A cloak or a dagger?

Hemolysin from uropathogenic Escherichia coli (UPEC) is a hemolytic and cytotoxic protein active against a broad range of species and cell types. Expression of hemolysin correlates with severity of infection, as up to 78% of UPEC isolates from pyelonephritis cases express hemolysin. Despite decades of research on hemolysin activity, the mechanism of intoxication and the function of hemolysin in UPEC infection remain elusive.

Integrin binding by Borrelia burgdorferi P66 facilitates dissemination but is not required for infectivity.

P66, a Borrelia burgdorferi surface protein with porin and integrin-binding activities, is essential for murine infection. The role of P66 integrin-binding activity in B. burgdorferi infection was investigated and found to affect transendothelial migration.

The β₃-integrin ligand of Borrelia burgdorferi is critical for infection of mice but not ticks.

P66 is a Borrelia burgdorferi surface protein with β₃ integrin binding and channel forming activities. In this study, the role of P66 in mammalian and tick infection was examined. B.

Adhesion mechanisms of Borrelia burgdorferi.

The Borrelia are widely distributed agents of Lyme disease and Relapsing Fever. All are vector-borne zoonotic pathogens, have segmented genomes, and enigmatic mechanisms of pathogenesis. Adhesion to mammalian and tick substrates is one pathogenic mechanism that has been widely studied.

Insight into the mechanism of human herpesvirus 7 U21-mediated diversion of class I MHC molecules to lysosomes.

The U21 open reading frame from human herpesvirus-7 encodes a membrane protein that associates with and redirects class I MHC molecules to the lysosomal compartment. The mechanism by which U21 accomplishes this trafficking excursion is unknown. Here we have examined the contribution of localization, glycosylation, domain structure, and the absence of substrate class I MHC molecules on the ability of U21 to traffic to lysosomes.

Effect of Borrelia burgdorferi OspC at the site of inoculation in mouse skin.

The Borrelia burgdorferi surface lipoprotein OspC is a critical virulence factor, but its precise role in the establishment of B. burgdorferi infection remains unclear. To determine whether OspC affects the host response at the site of inoculation of the bacterium, the recruitment of macrophages and neutrophils and the production of cytokines were examined at the site of infection by wild-type, ospC mutant, and complemented mutant B.