scholarly journals Antimicrobial Photodynamic Inactivation Inhibits Candida albicans Virulence Factors and ReducesIn VivoPathogenicity

2012 ◽  
Vol 57 (1) ◽  
pp. 445-451 ◽  
Author(s):  
Ilka Tiemy Kato ◽  
Renato Araujo Prates ◽  
Caetano Padial Sabino ◽  
Beth Burgwyn Fuchs ◽  
George P. Tegos ◽  
...  
Keyword(s):  
Candida Albicans ◽  
Virulence Factors ◽  
Sodium Dodecyl ◽  
Systemic Infection ◽  
Tube Formation ◽  
Photodynamic Inactivation ◽  
Content Type ◽  
Daughter Cells

ABSTRACTThe objective of this study was to evaluate whetherCandida albicansexhibits altered pathogenicity characteristics following sublethal antimicrobial photodynamic inactivation (APDI) and if such alterations are maintained in the daughter cells.C. albicanswas exposed to sublethal APDI by using methylene blue (MB) as a photosensitizer (0.05 mM) combined with a GaAlAs diode laser (λ 660 nm, 75 mW/cm2, 9 to 27 J/cm2).In vitro, we evaluated APDI effects onC. albicansgrowth, germ tube formation, sensitivity to oxidative and osmotic stress, cell wall integrity, and fluconazole susceptibility.In vivo, we evaluatedC. albicanspathogenicity with a mouse model of systemic infection. Animal survival was evaluated daily. Sublethal MB-mediated APDI reduced the growth rate and the ability ofC. albicansto form germ tubes compared to untreated cells (P< 0.05). Survival of mice systemically infected withC. albicanspretreated with APDI was significantly increased compared to mice infected with untreated yeast (P< 0.05). APDI increasedC. albicanssensitivity to sodium dodecyl sulfate, caffeine, and hydrogen peroxide. The MIC for fluconazole forC. albicanswas also reduced following sublethal MB-mediated APDI. However, none of those pathogenic parameters was altered in daughter cells ofC. albicanssubmitted to APDI. These data suggest that APDI may inhibit virulence factors and reducein vivopathogenicity ofC. albicans. The absence of alterations in daughter cells indicates that APDI effects are transitory. The MIC reduction for fluconazole following APDI suggests that this antifungal could be combined with APDI to treatC. albicansinfections.

scholarly journals Blue Dye and Red Light, a Dynamic Combination for Prophylaxis and Treatment of Cutaneous Candida albicans Infections in Mice

2011 ◽  
Vol 55 (12) ◽  
pp. 5710-5717 ◽  
Author(s):  
Tianhong Dai ◽  
Vida J. Bil de Arce ◽  
George P. Tegos ◽  
Michael R. Hamblin
Keyword(s):  
Methylene Blue ◽  
Candida Albicans ◽  
Bioluminescence Imaging ◽  
Red Light ◽  
Blue Dye ◽  
Photodynamic Inactivation ◽  
Content Type ◽  
Skin Abrasion

ABSTRACTThe objective of this study was to investigate photodynamic therapy (PDT), using blue dye and red light, for prophylaxis and treatment of cutaneousCandida albicansinfections in mice. A mouse model of skin abrasion infected withC. albicanswas developed by inoculating wounds measuring 1.2 cm by 1.2 cm with 106or 107CFU. The use of a luciferase-expressing strain ofC. albicansallowed real-time monitoring of the extent of infection in mice noninvasively through bioluminescence imaging. The phenothiazinium salts toluidine blue O (TBO), methylene blue (MB), and new methylene blue (NMB) were compared as photosensitizers (PS) for the photodynamic inactivation ofC. albicansin vitro. PDTin vivowas initiated either at 30 min or at 24 h after fungal inoculation to investigate the efficacies of PDT for both prophylaxis and treatment of infections. Light at 635 ± 15 nm or 660 ± 15 nm was delivered with a light dose of 78 J/cm2(for PDT at 30 min postinfection) or 120 J/cm2(for PDT at 24 h postinfection) in multiple exposures with bioluminescence imaging taking place after each exposure of light.In vitrostudies showed that NMB was superior to TBO and MB as the PS in the photodynamic inactivation ofC. albicans. The efficacy of PDT was related to the ratio of PS concentration to fungal cell density. PDTin vivoinitiated either at 30 min or at 24 h postinfection significantly reducedC. albicansburden in the infected mouse skin abrasion wounds. These data suggest that PDT is a viable approach for prophylaxis and treatment of cutaneousC. albicansinfections.

scholarly journals The Novel Arylamidine T-2307 MaintainsIn VitroandIn VivoActivity against Echinocandin-Resistant Candida albicans

2014 ◽  
Vol 59 (2) ◽  
pp. 1341-1343 ◽  
Author(s):  
Nathan P. Wiederhold ◽  
Laura K. Najvar ◽  
Annette W. Fothergill ◽  
Rosie Bocanegra ◽  
Marcos Olivo ◽  
...  
Keyword(s):  
Body Weight ◽  
Candida Albicans ◽  
Invasive Candidiasis ◽  
Placebo Control ◽  
The Novel ◽  
Content Type ◽  
Fungal Burden ◽  
Potential Use

ABSTRACTWe evaluated thein vitroandin vivoactivities of the investigational arylamidine T-2307 against echinocandin-resistantCandida albicans. T-2307 demonstrated potentin vitroactivity, and daily subcutaneous doses between 0.75 and 6 mg/kg of body weight significantly improved survival and reduced fungal burden compared to placebo control and caspofungin (10 mg/kg/day) in mice with invasive candidiasis caused by an echinocandin-resistant strain. Thus, T-2307 may have potential use in the treatment of echinocandin-resistantC. albicansinfections.

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 A Conserved PapB Family Member, TosR, Regulates Expression of the Uropathogenic Escherichia coli RTX Nonfimbrial Adhesin TosA while Conserved LuxR Family Members TosE and TosF Suppress Motility

2014 ◽  
Vol 82 (9) ◽  
pp. 3644-3656 ◽  
Author(s):  
Michael D. Engstrom ◽  
Christopher J. Alteri ◽  
Harry L. T. Mobley
Keyword(s):  
Escherichia Coli ◽  
Urinary Tract ◽  
Virulence Factors ◽  
Upper Urinary Tract ◽  
Host Cells ◽  
Promoter Regions ◽  
Content Type ◽  
Tract Infections

ABSTRACTA heterogeneous subset of extraintestinal pathogenicEscherichia coli(ExPEC) strains, referred to as uropathogenicE. coli(UPEC), causes most uncomplicated urinary tract infections. However, no core set of virulence factors exists among UPEC strains. Instead, the focus of the analysis of urovirulence has shifted to studying broad classes of virulence factors and the interactions between them. For example, the RTX nonfimbrial adhesin TosA mediates adherence to host cells derived from the upper urinary tract. The associatedtosoperon is well expressedin vivobut poorly expressedin vitroand encodes TosCBD, a predicted type 1 secretion system. TosR and TosEF are PapB and LuxR family transcription factors, respectively; however, no role has been assigned to these potential regulators. Thus, the focus of this study was to determine how TosR and TosEF regulatetosAand affect the reciprocal expression of adhesins and flagella. Among a collection of sequenced UPEC strains, 32% (101/317) were found to encode TosA, and nearly all strains (91% [92/101]) simultaneously carried the putative regulatory genes. Deletion oftosRalleviatestosArepression. Thetospromoter was localized upstream oftosRusing transcriptional fusions of putative promoter regions withlacZ. TosR binds to this region, affecting a gel shift. A 100-bp fragment 220 to 319 bp upstream oftosRinhibits binding, suggesting localization of the TosR binding site. TosEF, on the other hand, downmodulate motility when overexpressed by preventing the expression offliC, encoding flagellin. Deletion oftosEFincreased motility. Thus, we present an additional example of the reciprocal control of adherence and motility.

scholarly journals Symbiotic Relationship between Streptococcus mutans and Candida albicans Synergizes Virulence of Plaque BiofilmsIn Vivo

2014 ◽  
Vol 82 (5) ◽  
pp. 1968-1981 ◽  
Author(s):  
Megan L. Falsetta ◽  
Marlise I. Klein ◽  
Punsiri M. Colonne ◽  
Kathleen Scott-Anne ◽  
Stacy Gregoire ◽  
...  
Keyword(s):  
Candida Albicans ◽  
Dental Caries ◽  
Streptococcus Mutans ◽  
Bacterial Pathogen ◽  
Single Species ◽  
Content Type ◽  
3 Dimensional ◽  
Biofilm Development

ABSTRACTStreptococcus mutansis often cited as the main bacterial pathogen in dental caries, particularly in early-childhood caries (ECC).S. mutansmay not act alone;Candida albicanscells are frequently detected along with heavy infection byS. mutansin plaque biofilms from ECC-affected children. It remains to be elucidated whether this association is involved in the enhancement of biofilm virulence. We showed that the ability of these organisms together to form biofilms is enhancedin vitroandin vivo. The presence ofC. albicansaugments the production of exopolysaccharides (EPS), such that cospecies biofilms accrue more biomass and harbor more viableS. mutanscells than single-species biofilms. The resulting 3-dimensional biofilm architecture displays sizeableS. mutansmicrocolonies surrounded by fungal cells, which are enmeshed in a dense EPS-rich matrix. Using a rodent model, we explored the implications of this cross-kingdom interaction for the pathogenesis of dental caries. Coinfected animals displayed higher levels of infection and microbial carriage within plaque biofilms than animals infected with either species alone. Furthermore, coinfection synergistically enhanced biofilm virulence, leading to aggressive onset of the disease with rampant carious lesions. Ourin vitrodata also revealed that glucosyltransferase-derived EPS is a key mediator of cospecies biofilm development and that coexistence withC. albicansinduces the expression of virulence genes inS. mutans(e.g.,gtfB,fabM). We also found thatCandida-derived β1,3-glucans contribute to the EPS matrix structure, while fungal mannan and β-glucan provide sites for GtfB binding and activity. Altogether, we demonstrate a novel mutualistic bacterium-fungus relationship that occurs at a clinically relevant site to amplify the severity of a ubiquitous infectious disease.

scholarly journals The HtrA-Like Protease CD3284 Modulates Virulence of Clostridium difficile

2014 ◽  
Vol 82 (10) ◽  
pp. 4222-4232 ◽  
Author(s):  
Dennis Bakker ◽  
Anthony M. Buckley ◽  
Anne de Jong ◽  
Vincent J. C. van Winden ◽  
Joost P. A. Verhoeks ◽  
...  
Keyword(s):  
Clostridium Difficile ◽  
Virulence Factors ◽  
Pathogenic Bacteria ◽  
Microarray Data Analysis ◽  
Toxin A ◽  
Hamster Model ◽  
Golden Syrian Hamster ◽  
Content Type

ABSTRACTIn the past decade,Clostridium difficilehas emerged as an important gut pathogen. Symptoms ofC. difficileinfection range from mild diarrhea to pseudomembranous colitis. Besides the two main virulence factors toxin A and toxin B, other virulence factors are likely to play a role in the pathogenesis of the disease. In other Gram-positive and Gram-negative pathogenic bacteria, conserved high-temperature requirement A (HtrA)-like proteases have been shown to have a role in protein homeostasis and quality control. This affects the functionality of virulence factors and the resistance of bacteria to (host-induced) environmental stresses. We found that theC. difficile630 genome encodes a single HtrA-like protease (CD3284; HtrA) and have analyzed its rolein vivoandin vitrothrough the creation of an isogenic ClosTron-basedhtrAmutant ofC. difficilestrain 630Δerm(wild type). In contrast to the attenuated phenotype seen withhtrAdeletion in other pathogens, this mutant showed enhanced virulence in the Golden Syrian hamster model of acuteC. difficileinfection. Microarray data analysis showed a pleiotropic effect ofhtrAon the transcriptome ofC. difficile, including upregulation of the toxin A gene. In addition,the htrAmutant showed reduced spore formation and adherence to colonic cells. Together, our data show thathtrAcan modulate virulence inC. difficile.

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 Deletion of the ATP2 Gene in Candida albicans Blocks Its Escape From Macrophage Clearance

2021 ◽  
Vol 11 ◽  
Author(s):  
Yishan Zhang ◽  
Chuanyan Tang ◽  
Zhanpeng Zhang ◽  
Shuixiu Li ◽  
Yajing Zhao ◽  
...  
Keyword(s):  
Candida Albicans ◽  
Drug Target ◽  
Fungal Infections ◽  
Carbon Sources ◽  
Systemic Infection ◽  
Invasive Infection ◽  
First Line ◽  
Dramatic Decrease

Macrophages provide the first-line defense against invasive fungal infections and, therefore, escape from macrophage becomes the basis for the establishment of Candida albicans invasive infection. Here, we found that deletion of ATP2 (atp2Δ/Δ) in C. albicans resulted in a dramatic decrease from 69.2% (WT) to 1.2% in the escape rate in vitro. The effect of ATP2 on macrophage clearance stands out among the genes currently known to affect clearance. In the normal mice, the atp2Δ/Δ cells were undetectable in major organs 72 h after systemic infection, while WT cells persisted in vivo. However, in the macrophage-depleted mice, atp2Δ/Δ could persist for 72 h at an amount comparable to that at 24 h. Regarding the mechanism, WT cells sustained growth and switched to hyphal form, which was more conducive to escape from macrophages, in media that mimic the glucose-deficient environment in macrophages. In contrast, atp2Δ/Δ cells can remained viable but were unable to complete morphogenesis in these media, resulting in them being trapped within macrophages in the yeast form. Meanwhile, atp2Δ/Δ cells were killed by oxidative stress in alternative carbon sources by 2- to 3-fold more than WT cells. Taken together, ATP2 deletion prevents C. albicans from escaping macrophage clearance, and therefore ATP2 has a functional basis as a drug target that interferes with macrophage clearance.

scholarly journals Application of Hydro-ethanol Extract of Tithonia diversifolia (Hemsl) in the Treatment of Experimental Murine Oral Candidiasis

2019 ◽  
pp. 1-10
Author(s):  
Oluwole Moses David ◽  
Margaret Olutayo Alese ◽  
Tobi Oyewole ◽  
Oluwole Ojo Alese ◽  
Adekunle Adegbuyi ◽  
...  
Keyword(s):  
Candida Albicans ◽  
Virulence Factors ◽  
Oral Candidiasis ◽  
Ethanolic Extract ◽  
Alcoholic Extract ◽  
Tithonia Diversifolia ◽  
Candida Spp ◽  
Oral Infections

Background: Oral infection caused by Candida spp. is a major healthcare problem in dental and oral care. Treatment failure has been reported in cases of oral candidiasis as a result of resistance to common antifungals. Aim and Objective: In this study, the in vitro and in vivo activities of extract of Tithonia diversifolia against virulence factor-borne and antifungal resistant-Candida albicans were investigated. Candida albicans was isolated from the saliva of patients attending a tertiary hospital in Ekiti State. Methodology: Standard methods were used to determine the presence of virulence factors in the isolates. In vitro and in vivo anti-candidal activities of the hydro-ethanolic extract of T. diversifolia were also tested on the test fungus. Results: The virulence factors have varying percentage of occurrence in all the isolates with catalase having the highest. Itraconazole and nystatin were not effective against the isolates. Out of the six isolates selected (based on antifungal resistance) only three produced strong biofilm. The reduction in the population of the test organisms by the extract was time and concentration dependent. At the end of candidal challenge and treatment assays, extract of T. diversifolia has lower anti-candidal property compared to nystatin. Conclusion: This study has shown that C. albicans associated with the mouth carries virulence factors and are resistant to common antifungals. In this work, we noticed antifungal effects of hydro-alcoholic extract of T. diversifolia on C. albicans associated with oral infections.

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