scholarly journals Quorum Sensing in the Dimorphic FungusCandida albicans Is Mediated by Farnesol

2001 ◽  
Vol 67 (7) ◽  
pp. 2982-2992 ◽  
Author(s):  
Jacob M. Hornby ◽  
Ellen C. Jensen ◽  
Amber D. Lisec ◽  
Joseph J. Tasto ◽  
Brandon Jahnke ◽  
...  
Keyword(s):  
Quorum Sensing ◽  
Chemical Nature ◽  
Tube Formation ◽  
Cross Reactivity ◽  
Inoculum Size ◽  
Cellular Growth ◽  
Farnesyl Pyrophosphate ◽  
Dimorphic Fungus ◽  
Fetal Bovine ◽  
Mycelial Development

ABSTRACT The inoculum size effect in the dimorphic fungus Candida albicans results from production of an extracellular quorum-sensing molecule (QSM). This molecule prevents mycelial development in both a growth morphology assay and a differentiation assay using three chemically distinct triggers for germ tube formation (GTF): l-proline, N-acetylglucosamine, and serum (either pig or fetal bovine). In all cases, the presence of QSM prevents the yeast-to-mycelium conversion, resulting in actively budding yeasts without influencing cellular growth rates. QSM exhibits general cross-reactivity within C. albicans in that supernatants from strain A72 are active on five other strains ofC. albicans and vice versa. The QSM excreted by C. albicans is farnesol (C15H26O; molecular weight, 222.37). QSM is extracellular, and is produced continuously during growth and over a temperature range from 23 to 43�C, in amounts roughly proportional to the CFU/milliliter. Production is not dependent on the type of carbon source nor nitrogen source or on the chemical nature of the growth medium. Both commercial mixed isomer and (E,E)-farnesol exhibited QSM activity (the ability to prevent GTF) at a level sufficient to account for all the QSM activity present in C. albicans supernatants, i.e., 50% GTF at ca. 30 to 35 μM. Nerolidol was ca. two times less active than farnesol. Neither geraniol (C10), geranylgeraniol (C20), nor farnesyl pyrophosphate had any QSM activity.

scholarly journals Inoculum Size Effect in Dimorphic Fungi: Extracellular Control of Yeast-Mycelium Dimorphism in Ceratocystis ulmi

2004 ◽  
Vol 70 (3) ◽  
pp. 1356-1359 ◽  
Author(s):  
Jacob M. Hornby ◽  
Sarah M. Jacobitz-Kizzier ◽  
Donna J. McNeel ◽  
Ellen C. Jensen ◽  
David S. Treves ◽  
...  
Keyword(s):  
Quorum Sensing ◽  
Size Effect ◽  
Organic Solvent ◽  
Inoculum Size ◽  
Dutch Elm Disease ◽  
Sulfur Source ◽  
Dimorphic Fungus ◽  
Promoting Effect ◽  
Dimorphic Fungi ◽  
Methyl Donors

ABSTRACT We studied the inoculum size effect in Ceratocystis ulmi, the dimorphic fungus that causes Dutch elm disease. In a defined glucose-proline-salts medium, cells develop as budding yeasts when inoculated at ≥106 spores per ml and as mycelia when inoculated at <106 spores per ml. The inoculum size effect was not influenced by inoculum spore type, age of the spores, temperature, pH, oxygen availability, trace metals, sulfur source, phosphorous source, or the concentration of glucose or proline. Similarly, it was not influenced by added adenosine, reducing agents, methyl donors, amino sugars, fatty acids, or carbon dioxide. Instead, growing cells excreted an unknown quorum-sensing factor that caused a morphological shift from mycelia to budding yeasts. This yeast-promoting effect is abolished if it is extracted with an organic solvent such as ethyl acetate. The quorum-sensing activity acquired by the organic solvent could be added back to fresh medium in a dose-dependent fashion. The quorum-sensing activity in C. ulmi spent medium was specific for C. ulmi and had no effect on the dimorphic fungus Candida albicans or the photomorphogenic fungus Penicillium isariaeforme. In addition, farnesol, the quorum-sensing molecule produced by C. albicans, did not inhibit mycelial development of C. ulmi when present at concentrations of up to 100 μM. We conclude that the inoculum size effect is a manifestation of a quorum-sensing system that is mediated by an excreted extracellular molecule, and we suggest that quorum sensing is a general phenomenon in dimorphic fungi.

scholarly journals Striking up the conversation: quorum sensing in fungi

Fine Focus ◽  
2015 ◽  
Vol 1 (2) ◽  
pp. 139-151
Author(s):  
Brooke Martini ◽  
Cody Orr ◽  
Ginny Webb
Keyword(s):  
Quorum Sensing ◽  
Fungal Infections ◽  
Large Population ◽  
Pantothenic Acid ◽  
Opportunistic Pathogen ◽  
Fungal Species ◽  
Cellular Growth ◽  
Growth Morphology ◽  
Dimorphic Fungus ◽  
Diploid Cells

Quorum sensing is a form of communication observed in different species of microbes. Numerous studies have shown the ability of bacteria and fungi to carry out quorum sensing by releasing specific molecules to enable communication in a large population. Quorum sensing has been shown to influence growth, morphology, and other factors pertaining to virulence in pathogenic microbes. In this review, we address three important fungal species and explain how each fungus has a unique and dynamic way of communicating. Candida albicans is an opportunistic pathogen, or one that is part of the normal microbiota that can become pathogenic and cause several diseases. Here, we address two quorum sensing molecules (QSMs) identified by investigators. These chemicals are tyrosol and farnesol, which act together to control cellular growth, morphology and biofilm production. Another opportunistic fungal pathogen, Cryptococcus neoformans, has been shown to display quorum sensing activity by using pantothenic acid as well as a peptide called quorum sensing-like peptide 1. These molecules have both been shown to control growth rates of C. neoformans. Saccharomyces cerevisiae is another dimorphic fungus that uses QSMs, although it is nonpathogenic. Using two aromatic alcohols, phenylethanol and tryptophol, S. cerevisiae can alter pseudohyphal growth in diploid cells as well as invasive growth in haploid cells. By understanding more about the ways these organisms communicate, we present the potential for new and better targets for the treatment of fungal infections.

scholarly journals Fetal Bovine Serum-Derived Extracellular Vesicles Persist within Vesicle-Depleted Culture Media

2018 ◽  
Vol 19 (11) ◽  
pp. 3538 ◽  
Author(s):  
Brandon Lehrich ◽  
Yaxuan Liang ◽  
Pooya Khosravi ◽  
Howard Federoff ◽  
Massimo Fiandaca
Keyword(s):  
Cell Growth ◽  
Extracellular Vesicles ◽  
Bovine Serum ◽  
Culture Media ◽  
Fetal Bovine Serum ◽  
Cellular Growth ◽  
Primary Astrocyte ◽  
Fetal Bovine ◽  
Cell Growth And Viability

It is known that culture media (CM) promotes cellular growth, adhesion, and protects explanted primary brain cells from in vitro stresses. The fetal bovine serum (FBS) supplement used in most CM, however, contains significant quantities of extracellular vesicles (EVs) that confound quantitative and qualitative analyses from the EVs produced by the cultured cells. We quantitatively tested the ability of common FBS EV-depletion protocols to remove exogenous EVs from FBS-supplemented CM and evaluated the influence such methods have on primary astrocyte culture growth and viability. We assessed two methodologies utilized for FBS EV removal prior to adding to CM: (1) an 18-h ultracentrifugation (UC); and (2) a commercial EV-depleted FBS (Exo-FBS™). Our analysis demonstrated that Exo-FBS™ CM provided the largest depletion (75%) of total FBS EVs, while still providing 6.92 × 109 ± 1.39 × 108 EVs/mL. In addition, both UC and Exo-FBS™ CM resulted in poor primary astrocyte cell growth and viability in culture. The two common FBS EV-depletion methods investigated, therefore, not only contaminate in vitro primary cell-derived EV analyses, but also provide a suboptimal environment for primary astrocyte cell growth and viability. It appears likely that future CM optimization, using a serum-free alternative, might be required to advance analyses of cell-specific EVs isolated in vitro.

scholarly journals Enhanced Production of Farnesol by Candida albicans Treated with Four Azoles

2004 ◽  
Vol 48 (6) ◽  
pp. 2305-2307 ◽  
Author(s):  
Jacob M. Hornby ◽  
Kenneth W. Nickerson
Keyword(s):  
Candida Albicans ◽  
Clinical Isolates ◽  
Farnesyl Pyrophosphate ◽  
Dimorphic Fungus ◽  
Azole Antifungals ◽  
Appl Environ ◽  
Enhanced Production

ABSTRACT The dimorphic fungus Candida albicans excretes farnesol, which is produced enzymatically from the sterol biosynthetic intermediate farnesyl pyrophosphate. Inhibition of C. albicans by four azole antifungals, fluconazole, ketoconazole, miconazole, and clotrimazole, caused elevated farnesol production (10- to 45-fold). Furthermore, farnesol production occurs in both laboratory strains and clinical isolates (J. M. Hornby et al., Appl. Environ. Microbiol. 67:2982-2992, 2001) of C. albicans.

scholarly journals Bacterial Quorum Sensing Stabilizes Cooperation by Optimizing Growth Strategies

2016 ◽  
Vol 82 (22) ◽  
pp. 6498-6506 ◽  
Author(s):  
Eric L. Bruger ◽  
Christopher M. Waters
Keyword(s):  
Growth Rate ◽  
Quorum Sensing ◽  
Experimental Evidence ◽  
Fundamental Problem ◽  
Growth Yield ◽  
Cellular Growth ◽  
Growth Strategies ◽  
High Cell ◽  
Content Type ◽  
Cell Densities

ABSTRACTCommunication has been suggested as a mechanism to stabilize cooperation. In bacteria, chemical communication, termed quorum sensing (QS), has been hypothesized to fill this role, and extracellular public goods are often induced by QS at high cell densities. Here we show, with the bacteriumVibrio harveyi, that QS provides strong resistance against invasion of a QS defector strain by maximizing the cellular growth rate at low cell densities while achieving maximum productivity through protease upregulation at high cell densities. In contrast, QS mutants that act as defectors or unconditional cooperators maximize either the growth rate or the growth yield, respectively, and thus are less fit than the wild-type QS strain. Our findings provide experimental evidence that regulation mediated by microbial communication can optimize growth strategies and stabilize cooperative phenotypes by preventing defector invasion, even under well-mixed conditions. This effect is due to a combination of responsiveness to environmental conditions provided by QS, lowering of competitive costs when QS is not induced, and pleiotropic constraints imposed on defectors that do not perform QS.IMPORTANCECooperation is a fundamental problem for evolutionary biology to explain. Conditional participation through phenotypic plasticity driven by communication is a potential solution to this dilemma. Thus, among bacteria, QS has been proposed to be a proximate stabilizing mechanism for cooperative behaviors. Here, we empirically demonstrate that QS inV. harveyiprevents cheating and subsequent invasion by nonproducing defectors by maximizing the growth rate at low cell densities and the growth yield at high cell densities, whereas an unconditional cooperator is rapidly driven to extinction by defectors. Our findings provide experimental evidence that QS regulation prevents the invasion of cooperative populations by QS defectors even under unstructured conditions, and they strongly support the role of communication in bacteria as a mechanism that stabilizes cooperative traits.

scholarly journals Farnesol Biosynthesis in Candida albicans: Cellular Response to Sterol Inhibition by Zaragozic Acid B

2003 ◽  
Vol 47 (7) ◽  
pp. 2366-2369 ◽  
Author(s):  
Jacob M. Hornby ◽  
Bessie W. Kebaara ◽  
Kenneth W. Nickerson
Keyword(s):  
Candida Albicans ◽  
Cellular Response ◽  
Biosynthetic Pathway ◽  
Fungicidal Activity ◽  
Sterol Biosynthesis ◽  
Farnesyl Pyrophosphate ◽  
Dimorphic Fungus ◽  
Cell Extracts ◽  
Antifungal Antibiotics ◽  
Zaragozic Acid

ABSTRACT The dimorphic fungus Candida albicans produces farnesol as a quorum-sensing molecule that regulates cellular morphology. The biosynthetic origin of farnesol has been resolved by treating these cells with zaragozic acid B, a potent inhibitor of squalene synthase in the sterol biosynthetic pathway. Treatment with zaragozic acid B leads to an eightfold increase in the amount of farnesol produced by C. albicans. Furthermore, C. albicans cell extracts contain enzymatic activity to convert [3H]farnesyl pyrophosphate to [3H]farnesol. Many common antifungal antibiotics (e.g., zaragozic acids, azoles, and allylamines) target steps in sterol biosynthesis. We suggest that the fungicidal activity of zaragozic acid derives in large part from the accumulation of farnesol that accompanies the inhibition of sterol biosynthesis.

scholarly journals Development and Evaluation of a Latex Agglutination Test for the Serodiagnosis of Paracoccidioidomycosis

2011 ◽  
Vol 18 (4) ◽  
pp. 604-608 ◽  
Author(s):  
Fabíola Silveira-Gomes ◽  
Dayse Nogueira Sarmento ◽  
Thifany Mendes Pinto ◽  
Rosiane Ferreira Pimentel ◽  
Lívia Barreto Nepomuceno ◽  
...  
Keyword(s):  
Latex Particle ◽  
Paracoccidioides Brasiliensis ◽  
Cross Reactivity ◽  
Latex Agglutination ◽  
Dimorphic Fungus ◽  
Double Immunodiffusion ◽  
Serum Samples ◽  
Content Type ◽  
Healthy Donors ◽  
Low Costs

ABSTRACTParacoccidioidomycosis (PCM) is the most prevalent systemic mycosis in Latin America. It is caused by the dimorphic fungusParacoccidioides brasiliensis. The immunodiffusion (ID) test is one of the most widely used techniques for PCM serologic diagnosis due to the simplicity and low costs of its execution. However, it requires trained and qualified people to execute it. The purpose of this study was to evaluate a latex particle agglutination (LA) test for the detection of anti-P. brasiliensisantibodies by using pooled crude exoantigens from the fungus. Fifty-one serum samples obtained from patients with PCM were tested. Positivity was observed in 84% (43/51) of these patients, and the agglutination patterns varied from small clumps with a cloudy background to large clumps with a clear background. The antibody titer reactivity ranged from 1:2 to 1:64. Cross-reactivity was observed in sera from patients with aspergillosis, histoplasmosis, and nonfungal disease. Serum samples obtained from healthy donors were not reactive. The sensitivity and specificity of the LA test were 84% and 81%, respectively. When comparing the LA test with the double-immunodiffusion test, we found an agreement of 92%. Further work is needed to improve the performance of the LA assay before it can be proposed as a reliable diagnostic tool, mainly in laboratories with little infrastructure.

scholarly journals Emergomycosis, an Emerging Systemic Mycosis in Immunocompromised Patients: Current Trends and Future Prospects

2021 ◽  
Vol 8 ◽  
Author(s):  
Arghadip Samaddar ◽  
Anuradha Sharma
Keyword(s):  
Taxonomic Revision ◽  
Cross Reactivity ◽  
Antifungal Drugs ◽  
Epidemiological Surveillance ◽  
Dimorphic Fungus ◽  
Internal Transcribed Spacer Region ◽  
Serological Tests ◽  
Worldwide Distribution ◽  
Resource Limited ◽  
Disseminated Disease

Recently, the global emergence of emergomycosis, a systemic fungal infection caused by a novel dimorphic fungus Emergomyces species has been observed among immunocompromised individuals. Though initially classified under the genus Emmonsia, a taxonomic revision in 2017 based on DNA sequence analyses placed five Emmonsia-like fungi under a separate genus Emergomyces. These include Emergomyces pasteurianus, Emergomyces africanus, Emergomyces canadensis, Emergomyces orientalis, and Emergomyces europaeus. Emmonsia parva was renamed as Blastomyces parvus, while Emmonsia crescens and Emmonsia sola remained within the genus Emmonsia until a taxonomic revision in 2020 placed both the species under the genus Emergomyces. However, unlike other members of the genus, Emergomyces crescens and Emergomyces sola do not cause disseminated disease. The former causes adiaspiromycosis, a granulomatous pulmonary disease, while the latter has not been associated with human disease. So far, emergomycosis has been mapped across four continents: Asia, Europe, Africa and North America. However, considering the increasing prevalence of HIV/AIDS, it is presumed that the disease must have a worldwide distribution with many cases going undetected. Diagnosis of emergomycosis remains challenging. It should be considered in the differential diagnosis of histoplasmosis as there is considerable clinical and histopathological overlap between the two entities. Sequencing the internal transcribed spacer region of ribosomal DNA is considered as the gold standard for identification, but its application is compromised in resource limited settings. Serological tests are non-specific and demonstrate cross-reactivity with Histoplasma galactomannan antigen. Therefore, an affordable, accessible, and reliable diagnostic test is the need of the hour to enable its diagnosis in endemic regions and also for epidemiological surveillance. Currently, there are no consensus guidelines for the treatment of emergomycosis. The recommended regimen consists of amphotericin B (deoxycholate or liposomal formulation) for 1–2 weeks, followed by oral itraconazole for at least 12 months. This review elaborates the taxonomic, clinical, diagnostic, and therapeutic aspects of emergomycosis. It also enumerates several novel antifungal drugs which might hold promise in the treatment of this condition and therefore, can be potential areas of future studies.

scholarly journals Comparison of Phylogenetically Distinct Histoplasma Strains Reveals Evolutionarily Divergent Virulence Strategies

mBio ◽  
2014 ◽  
Vol 5 (4) ◽  
Author(s):  
Victoria E. Sepúlveda ◽  
Corinne L. Williams ◽  
William E. Goldman
Keyword(s):  
Cell Wall ◽  
North America ◽  
Phylogenetic Analyses ◽  
Clinical Manifestations ◽  
Inoculum Size ◽  
Sublethal Dose ◽  
Dimorphic Fungus ◽  
Content Type ◽  
Wide Range

ABSTRACTInfection with the dimorphic fungusHistoplasma capsulatumresults from the inhalation of contaminated soil. Disease outcome is variable and depends on the immune status of the host, number of organisms inhaled, and theH. capsulatumstrain.H. capsulatumis divided into seven distinct clades based on phylogenetic analyses, and strains from two separate clades have been identified in North America (denoted as NAm strains). We characterized anH. capsulatumisolate (WU24) from the NAm 1 lineage in relation to two other well-characterizedHistoplasmaisolates, the Panamanian strain G186A and the NAm 2 strain G217B. We determined that WU24 is a chemotype II strain and requires cell wall α-(1,3)-glucan for successfulin vitroinfection of macrophages. In a mouse model of histoplasmosis, WU24 exhibited a disease profile that was very similar to that of strain G186A at a high sublethal dose; however, at this dose G217B had markedly different kinetics. Surprisingly, infection with a lower dose mitigated many of the differences during the course of infection. The observed differences in fungal burden, disease kinetics, symptomology, and cytokine responses all indicate that there is a sophisticated relationship between host and fungus that drives the development and progression of histoplasmosis.IMPORTANCEHistoplasmosis has a wide range of clinical manifestations, presenting as mild respiratory distress, acute respiratory infection, or a life-threatening disseminated disease most often seen in immunocompromised patients. Additionally, the outcome appears to be dependent on the amount and strain of fungus inhaled. In this study, we characterized a recent clinicalH. capsulatumisolate that was collected from an HIV+individual in North America. In contrast to other isolates from the same lineage, this strain, WU24, infected both macrophages and wild-type mice. We determined that in contrast to many other North American strains, WU24 infection of macrophages is dependent on the presence of cell wall α-(1,3)-glucan. Surprisingly, comparison of WU24 with two previously characterized isolates revealed that many conclusions regarding relative strain virulence and certain hallmarks of histoplasmosis are dependent on the inoculum size.

scholarly journals Diversity in yeast–mycelium dimorphism response of the Dutch elm disease pathogens: the inoculum size effect

2016 ◽  
Vol 62 (6) ◽  
pp. 525-529 ◽  
Author(s):  
Marie-Ève Wedge ◽  
Erika Sayuri Naruzawa ◽  
Martha Nigg ◽  
Louis Bernier
Keyword(s):  
Quorum Sensing ◽  
Size Effect ◽  
Inoculum Size ◽  
Dutch Elm Disease ◽  
Dimorphic Fungi ◽  
Ophiostoma Ulmi ◽  
Signalling Molecules ◽  
A Cell ◽  
Different Strains ◽  
External Stimuli

Dutch elm disease (DED) is caused by the dimorphic fungi Ophiostoma ulmi, Ophiostoma novo-ulmi, and Ophiostoma himal-ulmi. A cell population density-dependent phenomenon related to quorum sensing was previously shown to affect the reversible transition from yeast-like to mycelial growth in liquid shake cultures of O. novo-ulmi NRRL 6404. Since the response to external stimuli often varies among DED fungal strains, we evaluated the effect of inoculum size on 8 strains of the 3 species of DED agents by determining the proportion of yeast and mycelium produced at different spore inoculum concentrations in defined liquid shake medium. The results show that not all DED fungi strains respond similarly to inoculum size effect, since variations were observed among strains. It is thus possible that the different strains belonging to phylogenetically close species use different signalling molecules or molecular signalling pathways to regulate their growth mode via quorum-sensing mechanisms.

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