scholarly journals Acetylcholine Protects against Candida albicans Infection by Inhibiting Biofilm Formation and Promoting Hemocyte Function in a Galleria mellonella Infection Model

2015 ◽  
Vol 14 (8) ◽  
pp. 834-844 ◽  
Author(s):  
Ranjith Rajendran ◽  
Elisa Borghi ◽  
Monica Falleni ◽  
Federica Perdoni ◽  
Delfina Tosi ◽  
...  
Keyword(s):  
Candida Albicans ◽  
Biofilm Formation ◽  
Galleria Mellonella ◽  
Inflammatory Responses ◽  
Fungal Infections ◽  
Infection Model ◽  
Content Type

ABSTRACT Both neuronal acetylcholine and nonneuronal acetylcholine have been demonstrated to modulate inflammatory responses. Studies investigating the role of acetylcholine in the pathogenesis of bacterial infections have revealed contradictory findings with regard to disease outcome. At present, the role of acetylcholine in the pathogenesis of fungal infections is unknown. Therefore, the aim of this study was to determine whether acetylcholine plays a role in fungal biofilm formation and the pathogenesis of Candida albicans infection. The effect of acetylcholine on C. albicans biofilm formation and metabolism in vitro was assessed using a crystal violet assay and phenotypic microarray analysis. Its effect on the outcome of a C. albicans infection, fungal burden, and biofilm formation were investigated in vivo using a Galleria mellonella infection model. In addition, its effect on modulation of host immunity to C. albicans infection was also determined in vivo using hemocyte counts, cytospin analysis, larval histology, lysozyme assays, hemolytic assays, and real-time PCR. Acetylcholine was shown to have the ability to inhibit C. albicans biofilm formation in vitro and in vivo . In addition, acetylcholine protected G. mellonella larvae from C. albicans infection mortality. The in vivo protection occurred through acetylcholine enhancing the function of hemocytes while at the same time inhibiting C. albicans biofilm formation. Furthermore, acetylcholine also inhibited inflammation-induced damage to internal organs. This is the first demonstration of a role for acetylcholine in protection against fungal infections, in addition to being the first report that this molecule can inhibit C. albicans biofilm formation. Therefore, acetylcholine has the capacity to modulate complex host-fungal interactions and plays a role in dictating the pathogenesis of fungal infections.

scholarly journals The Heat-Induced Molecular Disaggregase Hsp104 of Candida albicans Plays a Role in Biofilm Formation and Pathogenicity in a Worm Infection Model

2012 ◽  
Vol 11 (8) ◽  
pp. 1012-1020 ◽  
Author(s):  
Alessandro Fiori ◽  
Soňa Kucharíková ◽  
Gilmer Govaert ◽  
Bruno P. A. Cammue ◽  
Karin Thevissen ◽  
...  
Keyword(s):  
Candida Albicans ◽  
Stress Responses ◽  
Biofilm Formation ◽  
Fungal Pathogens ◽  
Elevated Temperatures ◽  
Structural Defects ◽  
Infection Model ◽  
Content Type

ABSTRACT The consequences of deprivation of the molecular chaperone Hsp104 in the fungal pathogen Candida albicans were investigated. Mutants lacking HSP104 became hypersusceptible to lethally high temperatures, similarly to the corresponding mutants of Saccharomyces cerevisiae , whereas normal susceptibility was restored upon reintroduction of the gene. By use of a strain whose only copy of HSP104 is an ectopic gene under the control of a tetracycline-regulated promoter, expression of Hsp104 prior to the administration of heat shock could be demonstrated to be sufficient to confer protection from the subsequent temperature increase. This result points to a key role for Hsp104 in orchestrating the cell response to elevated temperatures. Despite their not showing evident growth or morphological defects, biofilm formation by cells lacking HSP104 proved to be defective in two established in vitro models that use polystyrene and polyurethane as the substrates. Biofilms formed by the wild-type and HSP104 -reconstituted strains showed patterns of intertwined hyphae in the extracellular matrix. In contrast, biofilm formed by the hsp104 Δ/ hsp104 Δ mutant showed structural defects and appeared patchy and loose. Decreased virulence of the hsp104 Δ/ hsp104 Δ mutant was observed in the Caenorhabditis elegans infection model, in which high in vivo temperature does not play a role. In agreement with the view that stress responses in fungal pathogens may have evolved to provide niche-specific adaptation to environmental conditions, these results provide an indication of a temperature-independent role for Hsp104 in support of Candida albicans virulence, in addition to its key role in governing thermotolerance.

scholarly journals Anti-adhesive and anti-biofilm activity of NC-E08. In vitro and in vivo study using Galleria mellonella infection model

2019 ◽  
Author(s):  
Gabriela Fernanda Bombarda ◽  
Janaina de Cássia Orlandi Sardi ◽  
Pedro L. Rosalen ◽  
Josy G. Lazarini ◽  
Eder R. Paganini ◽  
...  
Keyword(s):  
Candida Albicans ◽  
Biofilm Formation ◽  
Early Childhood Caries ◽  
Galleria Mellonella ◽  
Infection Model ◽  
Oral Diseases ◽  
Antimicrobial Drugs ◽  
Structural Analogues

Biofilms are organized microbial communities formed from an ecological succession. Biofilm formation functions as a mechanism of virulence and favors the development of diseases, including oral diseases such as dental caries and periodontal disease, in which the microorganisms Streptococcus mutans and Candida albicans are closely related. Previous studies have shown that interactions between S. mutans and C. albicans are associated with the pathogenesis of early childhood caries (ECC). Therefore, there is a great interest in finding new prototypes for antimicrobial drugs, mainly for the development of structural analogues of chalcones, which constitute one of the largest classes of natural products belonging to the flavonoid family and are considered strategic molecules for this purpose.

scholarly journals Reversible Daptomycin Tolerance of Adherent Staphylococci in an Implant Infection Model

2011 ◽  
Vol 55 (7) ◽  
pp. 3510-3516 ◽  
Author(s):  
Anne-K. John ◽  
Mathias Schmaler ◽  
Nina Khanna ◽  
Regine Landmann
Keyword(s):  
Treatment Failure ◽  
Mutant Strain ◽  
Calcium Ions ◽  
Biofilm Formation ◽  
Infection Model ◽  
Content Type ◽  
Wall Components

ABSTRACTDaptomycin (DAP) is bactericidal against methicillin-resistantStaphylococcus aureus(MRSA)in vitro, but it failed to eradicate MRSA in an experimental model of implant-associated infection. We therefore investigated various factors which could explain treatment failure by evaluating DAP activity, including the role of different cell wall components, adherence, biofilm, and calcium ions (Ca2+)in vitroandin vivo. In the tissue cage infection model, DAP was active only prophylactically and against low inocula. To identify the mechanisms of treatment failure, thein vitroactivity of DAP against planktonic and adherent growingS. aureusandS. epidermidismutants, differing in their capacity of biofilm formation and adherence, was determined. For planktonic staphylococci, the MIC was 0.625 μg/ml. For adherent staphylococci, DAP reduced biofilms at 30 μg/ml. However, it did not kill adherent bacteria up to 500 μg/ml, independent of biofilm biosynthesis (theicamutant strain), nuclease (thenuc1/nuc2mutant strain), LPXTG-anchored adhesin (thesrtAmutant strain), autolysin (theatlmutant strain), or alanyl-LTA (thedltAmutant strain). Resistance of adherent staphylococci was not due to mutations of adherent bacteria, since staphylococci became DAP susceptible after detachment. Phenotypic tolerance was not explained by inactivation of DAP or inability of initial Ca2+-DAP complex formation. However, the addition of up to 100 mg/liter (2.5 mmol/liter) Ca2+gradually improved bactericidal activity toward adherent staphylococciin vitroand increased the prevention rate in the cage model from 40% to 60%. In summary, adherent staphylococci are resistant to DAP killing unless Ca2+is supplemented to physiologic concentrations.

scholarly journals Eap1p, an Adhesin That Mediates Candida albicans Biofilm Formation In Vitro and In Vivo

2007 ◽  
Vol 6 (6) ◽  
pp. 931-939 ◽  
Author(s):  
Fang Li ◽  
Michael J. Svarovsky ◽  
Amy J. Karlsson ◽  
Joel P. Wagner ◽  
Karen Marchillo ◽  
...  
Keyword(s):  
Candida Albicans ◽  
Cell Adhesion ◽  
Biofilm Formation ◽  
Fungal Infections ◽  
Gene Dosage ◽  
Venous Catheter ◽  
Flow Chamber ◽  
Dependent Manner

ABSTRACT Candida albicans is the leading cause of systemic fungal infections in immunocompromised humans. The ability to form biofilms on surfaces in the host or on implanted medical devices enhances C. albicans virulence, leading to antimicrobial resistance and providing a reservoir for infection. Biofilm formation is a complex multicellular process consisting of cell adhesion, cell growth, morphogenic switching between yeast form and filamentous states, and quorum sensing. Here we describe the role of the C. albicans EAP1 gene, which encodes a glycosylphosphatidylinositol-anchored, glucan-cross-linked cell wall protein, in adhesion and biofilm formation in vitro and in vivo. Deleting EAP1 reduced cell adhesion to polystyrene and epithelial cells in a gene dosage-dependent manner. Furthermore, EAP1 expression was required for C. albicans biofilm formation in an in vitro parallel plate flow chamber model and in an in vivo rat central venous catheter model. EAP1 expression was upregulated in biofilm-associated cells in vitro and in vivo. Our results illustrate an association between Eap1p-mediated adhesion and biofilm formation in vitro and in vivo.

scholarly journals Activity of the Pore-Forming Virulence Factor Listeriolysin O Is Reversibly Inhibited by Naturally Occurring S-Glutathionylation

2017 ◽  
Vol 85 (4) ◽  
Author(s):  
Jonathan L. Portman ◽  
Qiongying Huang ◽  
Michelle L. Reniere ◽  
Anthony T. Iavarone ◽  
Daniel A. Portnoy
Keyword(s):  
Protein Function ◽  
Inhibitory Effect ◽  
Cysteine Residue ◽  
Infection Model ◽  
Listeriolysin O ◽  
Content Type ◽  
Pore Forming Proteins

ABSTRACT Cholesterol-dependent cytolysins (CDCs) represent a family of homologous pore-forming proteins secreted by many Gram-positive bacterial pathogens. CDCs mediate membrane binding partly through a conserved C-terminal undecapeptide, which contains a single cysteine residue. While mutational changes to other residues in the undecapeptide typically have severe effects, mutation of the cysteine residue to alanine has minor effects on overall protein function. Thus, the role of this highly conserved reactive cysteine residue remains largely unknown. We report here that the CDC listeriolysin O (LLO), secreted by the facultative intracellular pathogen Listeria monocytogenes, was posttranslationally modified by S-glutathionylation at this conserved cysteine residue and that either endogenously synthesized or exogenously added glutathione was sufficient to form this modification. When recapitulated with purified protein in vitro, this modification completely ablated the activity of LLO, and this inhibitory effect was fully reversible by treatment with reducing agents. A cysteine-to-alanine mutation in LLO rendered the protein completely resistant to inactivation by S-glutathionylation, and a mutant expressing this mutation retained full hemolytic activity. A mutant strain of L. monocytogenes expressing the cysteine-to-alanine variant of LLO was able to infect and replicate within bone marrow-derived macrophages indistinguishably from the wild type in vitro, yet it was attenuated 4- to 6-fold in a competitive murine infection model in vivo. This study suggests that S-glutathionylation may represent a mechanism by which CDC-family proteins are posttranslationally modified and regulated and help explain an evolutionary pressure to retain the highly conserved undecapeptide cysteine.

scholarly journals Targeting Fibronectin To Disrupt In Vivo Candida albicans Biofilms

2016 ◽  
Vol 60 (5) ◽  
pp. 3152-3155 ◽  
Author(s):  
Jeniel E. Nett ◽  
Jonathan Cabezas-Olcoz ◽  
Karen Marchillo ◽  
Deane F. Mosher ◽  
David R. Andes
Keyword(s):  
Candida Albicans ◽  
Biofilm Formation ◽  
Drug Targets ◽  
Venous Catheter ◽  
Surface Adhesion ◽  
Inhibitory Protein ◽  
Content Type ◽  
Novel Target

ABSTRACTNew drug targets are of great interest for the treatment of fungal biofilms, which are routinely resistant to antifungal therapies. We theorized that the interaction ofCandida albicanswith matricellular host proteins would provide a novel target. Here, we show that an inhibitory protein (FUD) targetingCandida-fibronectin interactions disrupts biofilm formationin vitroandin vivoin a rat venous catheter model. The peptide appears to act by blocking the surface adhesion ofCandida, halting biofilm formation.

scholarly journals Oral Administration of the Broad-Spectrum Antibiofilm Compound Toremifene Inhibits Candida albicans and Staphylococcus aureus Biofilm FormationIn Vivo

2014 ◽  
Vol 58 (12) ◽  
pp. 7606-7610 ◽  
Author(s):  
Kaat De Cremer ◽  
Nicolas Delattin ◽  
Katrijn De Brucker ◽  
Annelies Peeters ◽  
Soña Kucharíková ◽  
...  
Keyword(s):  
Staphylococcus Aureus ◽  
Candida Albicans ◽  
Broad Spectrum ◽  
Staphylococcus Epidermidis ◽  
Biofilm Formation ◽  
Candida Krusei ◽  
Content Type ◽  
And Staphylococcus Aureus

ABSTRACTWe here report on thein vitroactivity of toremifene to inhibit biofilm formation of different fungal and bacterial pathogens, includingCandida albicans,Candida glabrata,Candida dubliniensis,Candida krusei,Pseudomonas aeruginosa,Staphylococcus aureus, andStaphylococcus epidermidis. We validated thein vivoefficacy of orally administered toremifene againstC. albicans and S. aureusbiofilm formation in a rat subcutaneous catheter model. Combined, our results demonstrate the potential of toremifene as a broad-spectrum oral antibiofilm compound.

scholarly journals Intravital Imaging of Candida albicans Identifies Differential In Vitro and In Vivo Filamentation Phenotypes for Transcription Factor Deletion Mutants

mSphere ◽  
2021 ◽  
Author(s):  
Rohan S. Wakade ◽  
Manning Huang ◽  
Aaron P. Mitchell ◽  
Melanie Wellington ◽  
Damian J. Krysan
Keyword(s):  
Candida Albicans ◽  
Fungal Infections ◽  
Deletion Mutants ◽  
Filamentous Form ◽  
Content Type ◽  
Yeast Form ◽  
Common Causes ◽  
Do So

Candida albicans is one of the most common causes of fungal infections in humans. C. albicans undergoes a transition from a round yeast form to a filamentous form during infection, which is critical for its ability to cause disease. Although this transition has been studied in the laboratory for years, methods to do so in an animal model of infection have been limited.

scholarly journals Pancreatic Amylase Is an Environmental Signal for Regulation of Biofilm Formation and Host Interaction in Campylobacter jejuni

2015 ◽  
Vol 83 (12) ◽  
pp. 4884-4895 ◽  
Author(s):  
Waheed Jowiya ◽  
Katja Brunner ◽  
Sherif Abouelhadid ◽  
Haitham A. Hussain ◽  
Sean P. Nair ◽  
...  
Keyword(s):  
Campylobacter Jejuni ◽  
Biofilm Formation ◽  
Galleria Mellonella ◽  
Infection Model ◽  
Pancreatic Amylase ◽  
Content Type ◽  
Host Interaction ◽  
Food Borne ◽  
Epithelial Cell Lines

Campylobacter jejuniis a commensal bacterium in the intestines of animals and birds and a major cause of food-borne gastroenteritis in humans worldwide. Here we show that exposure to pancreatic amylase leads to secretion of an α-dextran byC. jejuniand that a secreted protease, Cj0511, is required. Exposure ofC. jejunito pancreatic amylase promotes biofilm formationin vitro, increases interaction with human epithelial cell lines, increases virulence in theGalleria mellonellainfection model, and promotes colonization of the chicken ileum. We also show that exposure to pancreatic amylase protectsC. jejunifrom stress conditionsin vitro, suggesting that the induced α-dextran may be important during transmission between hosts. This is the first evidence that pancreatic amylase functions as an interkingdom signal in an enteric microorganism.

scholarly journals Candida albicans PEP12 Is Required for Biofilm Integrity and In Vivo Virulence

2009 ◽  
Vol 9 (2) ◽  
pp. 266-277 ◽  
Author(s):  
Suresh K. A. Palanisamy ◽  
Melissa A. Ramirez ◽  
Michael Lorenz ◽  
Samuel A. Lee
Keyword(s):  
Candida Albicans ◽  
Lipolytic Activity ◽  
Infection Model ◽  
Temperature Sensitive ◽  
Null Mutant ◽  
Macrophage Infection ◽  
Content Type ◽  
Vacuolar Acidification

ABSTRACT To investigate the role of the prevacuolar secretion pathway in biofilm formation and virulence in Candida albicans, we cloned and analyzed the C. albicans homolog of the Saccharomyces cerevisiae prevacuolar trafficking gene PEP12. C. albicans PEP12 encodes a deduced t-SNARE that is 28% identical to S. cerevisiae Pep12p, and plasmids bearing C. albicans PEP12 complemented the abnormal vacuolar morphology and temperature-sensitive growth of an S. cerevisiae pep12 null mutant. The C. albicans pep12 Δ null mutant was defective in endocytosis and vacuolar acidification and accumulated 40- to 60-nm cytoplasmic vesicles near the plasma membrane. Secretory defects included increased extracellular proteolytic activity and absent lipolytic activity. The pep12Δ null mutant was more sensitive to cell wall stresses and antifungal agents than the isogenic complemented strain or the control strain DAY185. Notably, the biofilm formed by the pep12Δ mutant was reduced in overall mass and fragmented completely upon the slightest disturbance. The pep12Δ mutant was markedly reduced in virulence in an in vitro macrophage infection model and an in vivo mouse model of disseminated candidiasis. These results suggest that C. albicans PEP12 plays a key role in biofilm integrity and in vivo virulence.

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