Stress contingent changes in Hog1 pathway architecture and regulation in Candida albicans.

The Hog1 stress-activated protein kinase (SAPK) is a key mediator of stress resistance and virulence in Candida albicans. Hog1 activation via phosphorylation of the canonical TGY motif is mediated by the Pbs2 MAPKK, which itself is activated by the Ssk2 MAPKKK. Although this three-tiered SAPK signalling module is well characterised, it is unclear how Hog1 activation is regulated in response to different stresses.

Metabolic modelling as a powerful tool to identify critical components of Pneumocystis growth medium.

Establishing suitable in vitro culture conditions for microorganisms is crucial for dissecting their biology and empowering potential applications. However, a significant number of bacterial and fungal species, including Pneumocystis jirovecii, remain unculturable, hampering research efforts. P.

Cryo-electron microscopy structure of the di-domain core of polyketide synthase 13, essential for mycobacterial mycolic acid synthesis.

Mycobacteria are known for their complex cell wall, which comprises layers of peptidoglycan, polysaccharides and unusual fatty acids known as mycolic acids that form their unique outer membrane. Polyketide synthase 13 (Pks13) of , the bacterial organism causing tuberculosis, catalyses the last step of mycolic acid synthesis prior to export to and assembly in the cell wall. Due to its essentiality, Pks13 is a target for several novel anti-tubercular inhibitors, but its 3D structure and catalytic reaction mechanism remain to be fully elucidated.

Impact of secreted glucanases upon the cell surface and fitness of during colonisation and infection.

Host recognition of the pathogen-associated molecular pattern (PAMP), β-1,3-glucan, plays a major role in antifungal immunity. β-1,3-glucan is an essential component of the inner cell wall of the opportunistic pathogen . Most β-1,3-glucan is shielded by the outer cell wall layer of mannan fibrils, but some can become exposed at the cell surface.

Candida auris undergoes adhesin-dependent and -independent cellular aggregation.

Candida auris is a fungal pathogen of humans responsible for nosocomial infections with high mortality rates. High levels of resistance to antifungal drugs and environmental persistence mean these infections are difficult to treat and eradicate from a healthcare setting. Understanding the life cycle and the genetics of this fungus underpinning clinically relevant traits, such as antifungal resistance and virulence, is of the utmost importance to develop novel treatments and therapies.

Candida albicans N-Linked Mannans Potentiate the Induction of Trained Immunity via Dectin-2.

The interaction between the Candida albicans cell wall and pattern recognition receptors is crucial for the initiation of host immune responses, which, ultimately, contribute to the clearance of this pathogenic fungus. In the present study, we investigate the ability of C. albicans mannans to modulate immune response and induce innate immune memory (also termed trained immunity).

Characterising phagocytes and measuring phagocytosis from live Galleria mellonella larvae.

Over the last 20 years, the larva of the greater waxmoth, , has rapidly increased in popularity as an mammalian replacement model organism for the study of human pathogens. Experimental readouts of response to infection are most often limited to observing the melanization cascade and quantifying larval death and, whilst transcriptomic and proteomic approaches, and methods to determine microbial load are also used, a more comprehensive toolkit of profiling infection over time could transform the applicability of this model. As an invertebrate, harbour an innate immune system comprised of both humoral components and a repertoire of innate immune cells - termed haemocytes.

Slicing through the challenge of maintaining in the laboratory.

is a major fungal pathogen of humans that causes life-threatening lung infections in immunocompromised individuals. Despite its huge global impact upon human health, our understanding of the pathobiology of this deadly fungus remains extremely limited, largely because it is not yet possible to cultivate independently of the host. However, a recent paper by Munyonho et al.

A CO sensing module modulates β-1,3-glucan exposure in .

Microbial species capable of co-existing with healthy individuals, such as the commensal fungus exploit multifarious strategies to evade our immune defenses. These strategies include the masking of immunoinflammatory pathogen-associated molecular patterns (PAMPs) at their cell surface. We reported previously that actively reduces the exposure of the proinflammatory PAMP, β-1,3-glucan, at its cell surface in response to host-related signals such as lactate and hypoxia.

Valsalva Maneuver to Identify Dermal Bleeders after Paramedian Flap Elevation Under Local Anesthesia.

The paramedian forehead flap (PFF) provides a reliable reconstruction option for complex nasal tip defects. The robust blood supply from a well perfused pedicle allows for reconstruction of large defects of the nasal tip for which simpler methods/techniques would provide inadequate coverage or result in inferior cosmesis. A well-designed PFF containing the supratrochlear artery inherently predisposes to small vessel bleeding from the pedicles cut edge.

Quantitation of glyphosate, glufosinate, and AMPA in drinking water and surface waters using direct injection and charged-surface ultra-high performance liquid chromatography-tandem mass spectrometry.

Herbicides glyphosate (N-(phosphonomethyl)glycine) and glufosinate (2-amino-4-(hydroxymethylphosphinyl)butanoic acid) and the main transformation product of glyphosate, aminomethanephosphonic acid (AMPA), are challenging to analyze for in environmental samples. The quantitative method developed by this study adapts previously standardized dechlorination procedures coupled to a novel charged surface C column, ultra-high performance liquid chromatography-tandem mass spectrometry, polarity switching, and direct injection. The method was applied to chlorinated tap water, as well as river samples, collected in the City of Winnipeg and rural Manitoba, Canada.

The impact of ORF19.36.1 in the pathobiology of Candida albicans.

Background: Our previous proteomics data obtained from Candida albicans recovered after serial passage in a murine model of systemic infection revealed that Orf19.36.1 expression correlates with the virulence of the fungus.

A metagenomic library cloning strategy that promotes high-level expression of captured genes to enable efficient functional screening.

Functional screening of environmental DNA (eDNA) libraries is a potentially powerful approach to discover enzymatic "unknown unknowns", but is usually heavily biased toward the tiny subset of genes preferentially transcribed and translated by the screening strain. We have overcome this by preparing an eDNA library via partial digest with restriction enzyme FatI (cuts CATG), causing a substantial proportion of ATG start codons to be precisely aligned with strong plasmid-encoded promoter and ribosome-binding sequences. Whereas we were unable to select nitroreductases from standard metagenome libraries, our FatI strategy yielded 21 nitroreductases spanning eight different enzyme families, each conferring resistance to the nitro-antibiotic niclosamide and sensitivity to the nitro-prodrug metronidazole.

Fungal spore swelling and germination are restricted by the macrophage phagolysosome.

Many species of medically important fungi are prolific in the formation of asexual spores. Spores undergo a process of active swelling and cell wall remodelling before a germ tube is formed and filamentous growth ensues. Highly elongated germ tubes are known to be difficult to phagocytose and pose particular challenges for immune phagocytes.

Review of infection and bleeding complications in excisional skin surgery.

Skin excision is the primary treatment for skin cancer. Complication rates from skin cancer excision are generally low but rates of complications may vary according to procedural complexity, site and patient factors. It is important that patients are fully informed through the consent process considering individual circumstances, the Montgomery ruling and material risks.

CRISPR-based tools for targeted genetic manipulation in pathogenic species.

is an emerging fungal pathogen frequently associated with zoonotic transmission of sporotrichosis by contaminated cats. Within 25 years, the disease has spread not only throughout Brazil but now to neighboring countries in Latin America. Thermo-dimorphism, melanin, glycans, adhesins, and secreted vesicles have been associated with the ability of species to cause disease in the mammalian host.

Identification of a new DC-SIGN binding pentamannoside epitope within the complex structure of mannan.

The dendritic cell-specific intercellular adhesion molecule-3-grabbing non-integrin (DC-SIGN) is an innate immune C-type lectin receptor that recognizes carbohydrate-based pathogen associated with molecular patterns of various bacteria, fungi, viruses and protozoa. Although a range of highly mannosylated glycoproteins have been shown to induce signaling via DC-SIGN, precise structure of the recognized oligosaccharide epitope is still unclear. Using the array of oligosaccharides related to selected fragments of main fungal antigenic polysaccharides we revealed a highly specific pentamannoside ligand of DC-SIGN, consisting of α-(1 → 2)-linked mannose chains with one inner α-(1 → 3)-linked unit.

Glucose-enhanced oxidative stress resistance-A protective anticipatory response that enhances the fitness of Candida albicans during systemic infection.

Most microbes have developed responses that protect them against stresses relevant to their niches. Some that inhabit reasonably predictable environments have evolved anticipatory responses that protect against impending stresses that are likely to be encountered in their niches-termed "adaptive prediction". Unlike yeasts such as Saccharomyces cerevisiae, Kluyveromyces lactis and Yarrowia lipolytica and other pathogenic Candida species we examined, the major fungal pathogen of humans, Candida albicans, activates an oxidative stress response following exposure to physiological glucose levels before an oxidative stress is even encountered.