CO enhances the formation, nutrient scavenging and drug resistance properties of C. albicans biofilms.

C. albicans is the predominant human fungal pathogen and frequently colonises medical devices, such as voice prostheses, as a biofilm. It is a dimorphic yeast that can switch between yeast and hyphal forms in response to environmental cues, a property that is essential during biofilm establishment and maturation.

Nitric oxide (NO) elicits aminoglycoside tolerance in Escherichia coli but antibiotic resistance gene carriage and NO sensitivity have not co-evolved.

The spread of multidrug-resistance in Gram-negative bacterial pathogens presents a major clinical challenge, and new approaches are required to combat these organisms. Nitric oxide (NO) is a well-known antimicrobial that is produced by the immune system in response to infection, and numerous studies have demonstrated that NO is a respiratory inhibitor with both bacteriostatic and bactericidal properties. However, given that loss of aerobic respiratory complexes is known to diminish antibiotic efficacy, it was hypothesised that the potent respiratory inhibitor NO would elicit similar effects.

Ras signalling in pathogenic yeasts.

The small GTPase Ras acts as a master regulator of growth, stress response and cell death in eukaryotic cells. The control of Ras activity is fundamental, as highlighted by the oncogenic properties of constitutive forms of Ras proteins. Ras also plays a crucial role in the pathogenicity of fungal pathogens where it has been found to regulate a number of adaptions required for virulence.

CO sensing in fungi: at the heart of metabolic signaling.

Adaptation to the changing environmental CO levels is essential for all living cells. In particular, microorganisms colonizing and infecting the human body are exposed to highly variable concentrations, ranging from atmospheric 0.04 to 5% and more in blood and specific host niches.

Lipid Signaling via Pkh1/2 Regulates Fungal CO2 Sensing through the Kinase Sch9.

Unlabelled: Adaptation to alternating CO concentrations is crucial for all organisms. Carbonic anhydrases-metalloenzymes that have been found in all domains of life-enable fixation of scarce CO by accelerating its conversion to bicarbonate and ensure maintenance of cellular metabolism. In fungi and other eukaryotes, the carbonic anhydrase Nce103 has been shown to be essential for growth in air (~0.

Invasive rhino-orbito-cerebral mucormycosis in a diabetic patient - the need for prompt treatment.

Mucormycosis is a rare life threatening fungal infection predominately seen in immunocompromised or diabetic patients. The following case is of a known type II diabetic patient who presented with sepsis and sudden unilateral loss of vision secondary to infective rhino-orbito-cerebral mucormycosis. Treatment of the condition required extensive surgical intervention and medical management for a life saving outcome.

Candida biofilm formation on voice prostheses.

Laryngopharyngeal malignancy is treated with radiotherapy and/or surgery. When total laryngectomy is required, major laryngeal functions (phonation, airway control, swallowing and coughing) are affected. The insertion of a silicone rubber voice prosthesis in a surgically created tracheoesophageal puncture is the most effective method for voice rehabilitation.

A mitochondrial CO2-adenylyl cyclase-cAMP signalosome controls yeast normoxic cytochrome c oxidase activity.

Mitochondria, the major source of cellular energy in the form of ATP, respond to changes in substrate availability and bioenergetic demands by employing rapid, short-term, metabolic adaptation mechanisms, such as phosphorylation-dependent protein regulation. In mammalian cells, an intramitochondrial CO2-adenylyl cyclase (AC)-cyclic AMP (cAMP)-protein kinase A (PKA) pathway regulates aerobic energy production. One target of this pathway involves phosphorylation of cytochrome c oxidase (COX) subunit 4-isoform 1 (COX4i1), which modulates COX allosteric regulation by ATP.

Carbonic anhydrase inhibitors: inhibition of the β-class enzyme from the pathogenic yeast Candida glabrata with sulfonamides, sulfamates and sulfamides.

The fungal pathogen Candida glabrata encodes for a β-carbonic anhydrase (CA, EC 4.2.1.

Functional characterization of the small heat shock protein Hsp12p from Candida albicans.

Hsp12p is considered to be a small heat shock protein and conserved among fungal species. To investigate the expression of this heat shock protein in the fungal pathogen Candida albicans we developed an anti-CaHsp12p antibody. We show that this protein is induced during stationary phase growth and under stress conditions including heat shock, osmotic, oxidative and heavy metal stress.

Carbonic anhydrase regulation and CO(2) sensing in the fungal pathogen Candida glabrata involves a novel Rca1p ortholog.

Carbon dioxide (CO2) is a ubiquitous gas present at 0.0391% in atmospheric air and 5.5% in human blood.

The transcription factor Flo8 mediates CO2 sensing in the human fungal pathogen Candida albicans.

Physiological levels of CO(2) have a profound impact on prominent biological attributes of the major fungal pathogen of humans, Candida albicans. Elevated CO(2) induces filamentous growth and promotes white-to-opaque switching. However, the underlying molecular mechanisms of CO(2) sensing in C.

The bZIP transcription factor Rca1p is a central regulator of a novel CO₂ sensing pathway in yeast.

Like many organisms the fungal pathogen Candida albicans senses changes in the environmental CO(2) concentration. This response involves two major proteins: adenylyl cyclase and carbonic anhydrase (CA). Here, we demonstrate that CA expression is tightly controlled by the availability of CO(2) and identify the bZIP transcription factor Rca1p as the first CO(2) regulator of CA expression in yeast.

Dithiocarbamates are strong inhibitors of the beta-class fungal carbonic anhydrases from Cryptococcus neoformans, Candida albicans and Candida glabrata.

A series of N-mono- and N,N-disubstituted dithiocarbamates have been investigated as inhibitors of three β-carbonic anhydrases (CAs, EC 4.2.1.

Candida albicans developmental regulation: adenylyl cyclase as a coincidence detector of parallel signals.

In the healthy individual, Candida albicans is frequently found as a harmless commensal residing in the gastrointestinal tract. However, in the compromised patient, C. albicans may invade the body and cause disease that is associated with poor prognosis and high mortality.

Communication in fungi.

We will discuss fungal communication in the context of fundamental biological functions including mating, growth, morphogenesis, and the regulation of fungal virulence determinants. We will address intraspecies but also interkingdom signaling by systematically discussing the sender of the message, the molecular message, and receiver. Analyzing communication shows the close coevolution of fungi with organisms present in their environment giving insights into multispecies communication.

The quorum-sensing molecules farnesol/homoserine lactone and dodecanol operate via distinct modes of action in Candida albicans.

Living as a commensal, Candida albicans must adapt and respond to environmental cues generated by the mammalian host and by microbes comprising the natural flora. These signals have opposing effects on C. albicans, with host cues promoting the yeast-to-hyphal transition and bacteria-derived quorum-sensing molecules inhibiting hyphal development.

Carbonic anhydrase inhibitors. Inhibition of the β-class enzymes from the fungal pathogens Candida albicans and Cryptococcus neoformans with branched aliphatic/aromatic carboxylates and their derivatives.

The inhibition of the β-carbonic anhydrases (CAs, EC 4.2.1.

Natural product-based phenols as novel probes for mycobacterial and fungal carbonic anhydrases.

In order to discover novel probes that may help in the investigation and control of infectious diseases through a new mechanism of action, we have evaluated a library of phenol-based natural products (NPs) for enzyme inhibition against four recently characterized pathogen β-family carbonic anhydrases (CAs). These include CAs from Mycobacterium tuberculosis, Candida albicans, and Cryptococcus neoformans as well as α-family human CA I and CA II for comparison. Many of the NPs selectively inhibited the mycobacterial and fungal β-CAs, with the two best performing compounds displaying submicromolar inhibition with a preference for fungal over human CA inhibition of more than 2 orders of magnitude.

CO(2) acts as a signalling molecule in populations of the fungal pathogen Candida albicans.

When colonising host-niches or non-animated medical devices, individual cells of the fungal pathogen Candida albicans expand into significant biomasses. Here we show that within such biomasses, fungal metabolically generated CO(2) acts as a communication molecule promoting the switch from yeast to filamentous growth essential for C. albicans pathology.

Carbonic anhydrase inhibitors. The beta-carbonic anhydrases from the fungal pathogens Cryptococcus neoformans and Candida albicans are strongly inhibited by substituted-phenyl-1H-indole-5-sulfonamides.

A series of 2-(hydrazinocarbonyl)-3-substituted-phenyl-1H-indole-5-sulfonamides and 1-({[5-(aminosulfonyl)-3-phenyl-1H-indol-2-yl]carbonyl}amino)-2,4,6 trimethylpyridinium perchlorates possessing various 2-, 3- or 4-substituted phenyl groups with methyl-, halogeno- and methoxy-functionalities, as well as the perfluorophenyl moiety, have been evaluated as inhibitors of the beta-carbonic anhydrases (CAs, EC 4.2.1.

Carbonic anhydrase activators: Activation of the beta-carbonic anhydrase from the pathogenic yeast Candida glabrata with amines and amino acids.

The protein encoded by the NCE103 gene of Candida glabrata, a beta-carbonic anhydrase (CA, EC 4.2.1.

Carbonic anhydrase activators: activation of the beta-carbonic anhydrases from the pathogenic fungi Candida albicans and Cryptococcus neoformans with amines and amino acids.

The proteins encoded by the Nce103 genes of Candida albicans and Cryptococcus neoformans are catalytically active beta-carbonic anhydrases (CAs, EC 4.2.1.

A multi-protein complex controls cAMP signalling and filamentation in the fungal pathogen Candida albicans.

Candida albicans is an opportunistic fungal pathogen of humans. The ability of the fungus to grow as both yeast and filamentous forms is essential for its pathogenicity. Morphogenesis of C.

Quorum sensing and fungal-bacterial interactions in Candida albicans: a communicative network regulating microbial coexistence and virulence.

Microorganisms have evolved a complex signature of communication termed quorum sensing (QS), which is based on the exchange and sensing of low molecular- weight signal compounds. The ability to communicate within the microbial population gives the advantage to coordinate a groups behaviour leading to a higher fitness in the environment. The polymorphic fungus Candida albicans is an opportunistic human pathogen able to regulate virulence traits through the production of at least two QS signal molecules: farnesol and tyrosol.