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 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 In Vitro and In Vivo Anti-infective Potential of Thymol Against Early Childhood Caries Causing Dual Species Candida albicans and Streptococcus mutans

2021 ◽  
Vol 12 ◽  
Author(s):  
Arumugam Priya ◽  
Anthonymuthu Selvaraj ◽  
Dass Divya ◽  
Ramalingam Karthik Raja ◽  
Shunmugiah Karutha Pandian
Keyword(s):  
Early Childhood ◽  
Candida Albicans ◽  
Streptococcus Mutans ◽  
Early Childhood Caries ◽  
Galleria Mellonella ◽  
Biological Activities ◽  
Infective Potential ◽  
Childhood Caries

Early childhood caries (ECC), a severe form of caries due to cross-kingdom interaction of Candida albicans and Streptococcus mutans, is a serious childhood dental disease that affects majority of the children with poor background. The present study investigated the anti-infective potential of thymol against C. albicans and S. mutans dual species for the management of ECC. Thymol, a plant derivative of the monoterpene group, has been well known for its numerous biological activities. Thymol at 300 μg/ml concentration completely arrested growth and proliferation of dual species of C. albicans and S. mutans. Rapid killing efficacy of pathogens, within a span of 2 min, was observed in the time kill assay. In addition, at sub-inhibitory concentrations, thymol effectively diminished the biofilm formation and virulence of both C. albicans and S. mutans such as yeast-to-hyphal transition, hyphal-to-yeast transition, filamentation, and acidogenicity and acidurity, respectively, in single and dual species state. qPCR analysis was consistent with virulence assays. Also, through the invertebrate model system Galleria mellonella, in vivo toxicity and efficacy of the phytocompound was assessed, and it was found that no significant toxic effect was observed. Moreover, thymol was found to be proficient in diminishing the infection under single and dual state in in vivo condition. Overall, the results from the present study illustrate the anti-infective potential of thymol against the ECC-causing dual species, C. albicans and S. mutans, and the applicability of thymol in medicated dentifrice formulation.

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 Combined With Mefloquine, Resurrect Colistin Active in Colistin-Resistant Pseudomonas aeruginosa in vitro and in vivo

2021 ◽  
Vol 12 ◽  
Author(s):  
Xiaodong Zhang ◽  
Yining Zhao ◽  
Luozhu Feng ◽  
Mengxin Xu ◽  
Yiru Ge ◽  
...  
Keyword(s):  
Pseudomonas Aeruginosa ◽  
Synergistic Effect ◽  
Biofilm Formation ◽  
Galleria Mellonella ◽  
Synergistic Effects ◽  
Alternative Therapy ◽  
Multidrug Resistant ◽  
Infection Model

Colistin is a polymyxin antibiotic that is widely used for the treatment of multidrug resistant (MDR) Pseudomonas aeruginosa infections, as the last resort. Over the past few years, unreasonable use of antibiotics has resulted in an increase in MDR strains, including colistin-resistant P. aeruginosa. The present study aimed to explore the synergistic effects of mefloquine in combination with colistin for the treatment of colistin-resistant P. aeruginosa in vivo and in vitro. The synergistic effect of the combination of mefloquine and colistin was investigated in vitro using checkerboard method, time-killing assay, biofilm formation inhibition test, and biofilm eradication test. The study also explored the synergistic effects of this combination of drugs in vivo, using a Galleria mellonella infection model. The results for checkerboard method and time killing curve indicated that mefloquine in combination with colistin showed a good antibacterial activity. Furthermore, the combination of these two drugs inhibited biofilm formation and eradicated pre-formed mature biofilms. This synergistic effect was visualized using scanning electron microscopy (SEM), wherein the results showed that the combination of mefloquine and colistin reduced biofilm formation significantly. Further, the application of this combination of drugs to in vivo infection model significantly increased the survival rate of G. mellonella larvae. Altogether, the combination of mefloquine and colistin showed a good synergistic effect in vitro and in vivo, and highlighted its potential to be used as an alternative therapy for the treatment of colistin-resistant P. aeruginosa infection.

scholarly journals Candida albicans SET3 Plays a Role in Early Biofilm Formation, Interaction With Pseudomonas aeruginosa and Virulence in Caenorhabditis elegans

2021 ◽  
Vol 11 ◽  
Author(s):  
Ruan Fourie ◽  
Jacobus Albertyn ◽  
Olihile Sebolai ◽  
Onele Gcilitshana ◽  
Carolina H. Pohl
Keyword(s):  
Pseudomonas Aeruginosa ◽  
Candida Albicans ◽  
Caenorhabditis Elegans ◽  
Biofilm Formation ◽  
Transcriptional Analysis ◽  
Infection Model ◽  
Environmental Cues ◽  
Interspecies Interaction

The yeast Candida albicans exhibits multiple morphologies dependent on environmental cues. Candida albicans biofilms are frequently polymicrobial, enabling interspecies interaction through proximity and contact. The interaction between C. albicans and the bacterium, Pseudomonas aeruginosa, is antagonistic in vitro, with P. aeruginosa repressing the yeast-to-hyphal switch in C. albicans. Previous transcriptional analysis of C. albicans in polymicrobial biofilms with P. aeruginosa revealed upregulation of genes involved in regulation of morphology and biofilm formation, including SET3, a component of the Set3/Hos2 histone deacetylase complex (Set3C). This prompted the question regarding the involvement of SET3 in the interaction between C. albicans and P. aeruginosa, both in vitro and in vivo. We found that SET3 may influence early biofilm formation by C. albicans and the interaction between C. albicans and P. aeruginosa. In addition, although deletion of SET3 did not alter the morphology of C. albicans in the presence of P. aeruginosa, it did cause a reduction in virulence in a Caenorhabditis elegans infection model, even in the presence of P. aeruginosa.

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 Designing P. aeruginosa synthetic phages with reduced genomes

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Diana P. Pires ◽  
Rodrigo Monteiro ◽  
Dalila Mil-Homens ◽  
Arsénio Fialho ◽  
Timothy K. Lu ◽  
...  
Keyword(s):  
Galleria Mellonella ◽  
Antibacterial Properties ◽  
Genetically Engineered ◽  
In Vivo Studies ◽  
Infection Model ◽  
Promising Therapeutic Approach ◽  
Genes Encoding ◽  
First Time

AbstractIn the era where antibiotic resistance is considered one of the major worldwide concerns, bacteriophages have emerged as a promising therapeutic approach to deal with this problem. Genetically engineered bacteriophages can enable enhanced anti-bacterial functionalities, but require cloning additional genes into the phage genomes, which might be challenging due to the DNA encapsulation capacity of a phage. To tackle this issue, we designed and assembled for the first time synthetic phages with smaller genomes by knocking out up to 48% of the genes encoding hypothetical proteins from the genome of the newly isolated Pseudomonas aeruginosa phage vB_PaeP_PE3. The antibacterial efficacy of the wild-type and the synthetic phages was assessed in vitro as well as in vivo using a Galleria mellonella infection model. Overall, both in vitro and in vivo studies revealed that the knock-outs made in phage genome do not impair the antibacterial properties of the synthetic phages, indicating that this could be a good strategy to clear space from phage genomes in order to enable the introduction of other genes of interest that can potentiate the future treatment of P. aeruginosa infections.

Emergence of ceftazidime/avibactam resistance in KPC-3-producing Klebsiella pneumoniae in vivo

2019 ◽  
Vol 74 (11) ◽  
pp. 3211-3216 ◽  
Author(s):  
Stephan Göttig ◽  
Denia Frank ◽  
Eleonora Mungo ◽  
Anika Nolte ◽  
Michael Hogardt ◽  
...  
Keyword(s):  
Combination Therapy ◽  
Klebsiella Pneumoniae ◽  
Selection Pressure ◽  
Galleria Mellonella ◽  
Phenotypic Characterization ◽  
Infection Model ◽  
Development Of Resistance ◽  
Time Kill

Abstract Objectives The β-lactam/β-lactamase inhibitor combination ceftazidime/avibactam is active against KPC-producing Enterobacterales. Herein, we present molecular and phenotypic characterization of ceftazidime/avibactam resistance in KPC-3-producing Klebsiella pneumoniae that emerged in vivo and in vitro. Methods Sequence analysis of blaKPC-3 was performed from clinical and in vitro-generated ceftazidime/avibactam-resistant K. pneumoniae isolates. Time–kill kinetics and the Galleria mellonella infection model were applied to evaluate the activity of ceftazidime/avibactam and imipenem alone and in combination. Results The ceftazidime/avibactam-resistant clinical K. pneumoniae isolate revealed the amino acid change D179Y in KPC-3. Sixteen novel mutational changes in KPC-3 among in vitro-selected ceftazidime/avibactam-resistant isolates were described. Time–kill kinetics showed the emergence of a resistant subpopulation under selection pressure with either imipenem or ceftazidime/avibactam. However, combined selection pressure with imipenem plus ceftazidime/avibactam prevented the development of resistance and resulted in bactericidal activity. Concordantly, the G. mellonella infection model revealed that monotherapy with ceftazidime/avibactam is prone to select for resistance in vivo and that combination therapy with imipenem results in significantly better survival. Conclusions Ceftazidime/avibactam is a valuable antibiotic against MDR and carbapenem-resistant Enterobacterales. Based on time–kill kinetics as well as an in vivo infection model we postulate a combination therapy of ceftazidime/avibactam and imipenem as a strategy to prevent the development of ceftazidime/avibactam resistance in KPC-producing Enterobacterales in vivo.

scholarly journals Impact of the Order of Initiation of Fluconazole and Amphotericin B in Sequential or Combination Therapy on Killing of Candida albicans In Vitro and in a Rabbit Model of Endocarditis and Pyelonephritis

2001 ◽  
Vol 45 (2) ◽  
pp. 485-494 ◽  
Author(s):  
Arnold Louie ◽  
Pamela Kaw ◽  
Partha Banerjee ◽  
Weiguo Liu ◽  
George Chen ◽  
...  
Keyword(s):  
Candida Albicans ◽  
Amphotericin B ◽  
Induced Resistance ◽  
Rabbit Model ◽  
In Vivo Studies ◽  
Infection Model ◽  
Simultaneous Exposure ◽  
The Impact

ABSTRACT In vitro time-kill studies and a rabbit model of endocarditis and pyelonephritis were used to define the impact that the order of exposure of Candida albicans to fluconazole (FLC) and amphotericin B (AMB), as sequential and combination therapies, had on the susceptibility of C. albicans to AMB and on the outcome. The contribution of FLC-induced resistance to AMB for C. albicans also was assessed. In vitro, AMB monotherapy rapidly killed each of four C. albicans strains; FLC alone was fungistatic. Preincubation of these fungi with FLC for 18 h prior to exposure to AMB decreased their susceptibilities to AMB for 8 to >40 h. Induced resistance to AMB was transient, but the duration of resistance increased with the length of FLC preincubation. Yeast sequentially incubated with FLC followed by AMB plus FLC (FLC→AMB+FLC) showed fungistatic growth kinetics similar to that of fungi that were exposed to FLC alone. This antagonistic effect persisted for at least 24 h. Simultaneous exposure of C. albicans to AMB and FLC [AMB+FLC(simult)] demonstrated activity similar to that with AMB alone for AMB concentrations of ≥1 μg/ml; antagonism was seen using an AMB concentration of 0.5 μg/ml. The in vitro findings accurately predicted outcomes in our rabbit infection model. In vivo, AMB monotherapy and treatment with AMB for 24 h followed by AMB plus FLC (AMB→AMB+FLC) rapidly sterilized kidneys and cardiac vegetations. AMB+FLC(simult) and FLC→AMB treatments were slower in clearing fungi from infected tissues. FLC monotherapy and FLC→AMB+FLC were both fungistatic and were the least active regimens. No adverse interaction was observed between AMB and FLC for the AMB→FLC regimen. However, FLC→AMB treatment was slower than AMB alone in clearing fungi from tissues. Thus, our in vitro and in vivo studies both demonstrate that preexposure of C. albicans to FLC reduces fungal susceptibility to AMB. The length of FLC preexposure and whether AMB is subsequently used alone or in combination with FLC determine the duration of induced resistance to AMB.

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.

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