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Open AccessArticle

The Effect of Novel Heterocyclic Compounds on Cryptococcal Biofilm

by Maya Korem, Sarah Kagan and Itzhack Polacheck

J. Fungi 2017, 3(3), 42; https://doi.org/10.3390/jof3030042 - 20 Jul 2017

Cited by 7 | Viewed by 4124

Biofilm formation by microorganisms depends on their communication by quorum sensing, which is mediated by small diffusible signaling molecules that accumulate in the extracellular environment. During human infection, the pathogenic yeast Cryptococcus neoformans can form biofilm on medical devices, which protects the organism [...] Read more.

Biofilm formation by microorganisms depends on their communication by quorum sensing, which is mediated by small diffusible signaling molecules that accumulate in the extracellular environment. During human infection, the pathogenic yeast Cryptococcus neoformans can form biofilm on medical devices, which protects the organism and increases its resistance to antifungal agents. The aim of this study was to test two novel heterocyclic compounds, S-8 (thiazolidinedione derivative, TZD) and NA-8 (succinimide derivative, SI), for their anti-biofilm activity against strains of Cryptococcus neoformans and Cryptococcus gattii. Biofilms were formed in a defined medium in 96-well polystyrene plates and 8-well micro-slides. The effect of sub-inhibitory concentrations of S-8 and NA-8 on biofilm formation was measured after 48 h by a metabolic reduction assay and by confocal laser microscopy analysis using fluorescent staining. The formation and development of cryptococcal biofilms was inhibited significantly by these compounds in concentrations below the minimum inhibitory concentration (MIC) values. These compounds may have a potential role in preventing fungal biofilm development on indwelling medical devices or even as a therapeutic measure after the establishment of biofilm. Full article

(This article belongs to the Special Issue Fungal Biofilms)

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1069 KiB

Open AccessArticle

Activity of Amphotericin B and Anidulafungin Combined with Rifampicin, Clarithromycin, Ethylenediaminetetraacetic Acid, N-Acetylcysteine, and Farnesol against Candida tropicalis Biofilms

by Marcelo Ernesto Fernández-Rivero, José L. Del Pozo, Amparo Valentín, Araceli Molina De Diego, Javier Pemán and Emilia Cantón

J. Fungi 2017, 3(1), 16; https://doi.org/10.3390/jof3010016 - 22 Mar 2017

Cited by 18 | Viewed by 4639

Abstract

We evaluated the activity of (1) amphotericin-B (AMB), combined with rifampicin (RIF), clarithromycin (CLA), N-acetylcysteine (NAC), ethylenediaminetetraacetic acid (EDTA), and farnesol (FAR) (1000, 1000, 1000, 4000, and 30,000 mg/L, and 300 µM, respectively), against Candida tropicalis biofilms formed on polytetrafluoroethylene (PTFE) and [...] Read more.

We evaluated the activity of (1) amphotericin-B (AMB), combined with rifampicin (RIF), clarithromycin (CLA), N-acetylcysteine (NAC), ethylenediaminetetraacetic acid (EDTA), and farnesol (FAR) (1000, 1000, 1000, 4000, and 30,000 mg/L, and 300 µM, respectively), against Candida tropicalis biofilms formed on polytetrafluoroethylene (PTFE) and (2) anidulafungin (ANF) combined with the same compounds at 8, 10, 5, 40, and 30 mg/L, and 30 µM, respectively, against biofilms formed on titanium. Biofilm growth kinetics were performed in a CDC Biofilm Reactor (CBR). PTFE or titanium disks were removed from the CBR at 24, 48, 72, and 96 h to determine the Log₁₀CFU/cm². Killing kinetics were performed by adding the drugs to 24-h-mature biofilms (time 0). Disks were removed after 24, 48, and 72 h of drug exposure to determine Log₁₀CFU/cm². Viable cells in biofilms were 4.73 and 4.29 Log₁₀CFU/cm² on PTFE and titanium, respectively. Maximum Log₁₀ decreases in CFU/cm² depend on the combination and were: 3.53 (AMB + EDTA), 2.65 (AMB + RIF), 3.07 (AMB + NAC), 2.52 (AMB + CLA), 1.49 (AMB + FAR), 2.26 (ANF + EDTA), 2.45 (ANF + RIF), 2.47 (ANF + NAC), 1.52 (ANF + CLA), and 0.44 (ANF + FAR). In conclusion, EDTA, NAC, RIF, and CLA improve the activity of AMB and ANF against biofilms developed on both surfaces, which could be an effective strategy against C. tropicalis biofilm-related infections. Full article

(This article belongs to the Special Issue Fungal Biofilms)

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Open AccessArticle

Real-Time Approach to Flow Cell Imaging of Candida albicans Biofilm Development

by Andrew McCall and Mira Edgerton

J. Fungi 2017, 3(1), 13; https://doi.org/10.3390/jof3010013 - 06 Mar 2017

Cited by 14 | Viewed by 5331

Abstract

The ability of Candida albicans to form biofilms is a virulence factor that allows tissue attachment and subsequent infection of host tissues. Fungal biofilms have been particularly well studied, however the vast majority of these studies have been conducted under static conditions. Oral [...] Read more.

The ability of Candida albicans to form biofilms is a virulence factor that allows tissue attachment and subsequent infection of host tissues. Fungal biofilms have been particularly well studied, however the vast majority of these studies have been conducted under static conditions. Oral biofilms form in the presence of salivary flow, therefore we developed a novel flow system used for real-time imaging of fungal biofilm development. C. albicans wild-type (WT) cells readily attached to the substrate surface during the 2 h attachment phase, then formed heterogeneous biofilms after 18 h flow. Quantitative values for biomass, rates of attachment and detachment, and cell–cell adhesion events were obtained for C. albicans WT cells and for a hyperfilamentous mutant Δhog1. Attachment rates of C. albicans WT cells were nearly 2-fold higher than C. albicans Δhog1 cells, although Δhog1 cells formed 4-fold higher biomass. The reduced normalized detachment rate was the primary factor responsible for the increased biomass of Δhog1 biofilm, showing that cell detachment rates are an important predictor for ultimate biofilm mass under flow. Unlike static biofilms, C. albicans cells under constant laminar flow undergo continuous detachment and seeding that may be more representative of the development of in vivo biofilms. Full article

(This article belongs to the Special Issue Fungal Biofilms)

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Open AccessArticle

Comparative Efficacies of Antimicrobial Catheter Lock Solutions for Fungal Biofilm Eradication in an in Vitro Model of Catheter-Related Fungemia

by Joel Rosenblatt, Ruth A. Reitzel, Nylev Vargas-Cruz, Anne-Marie Chaftari, Ray Hachem and Issam I. Raad

J. Fungi 2017, 3(1), 7; https://doi.org/10.3390/jof3010007 - 10 Feb 2017

Cited by 10 | Viewed by 4668

Abstract

Fungal catheter-related bloodstream infections (CRBSIs)—primarily due to Candida species—account for over 12% of all CRBSIs, and have been progressively increasing in prevalence. They present significant health and economic burdens, and high mortality rates. Antimicrobial catheter lock solutions are an important prophylactic option for [...] Read more.

Fungal catheter-related bloodstream infections (CRBSIs)—primarily due to Candida species—account for over 12% of all CRBSIs, and have been progressively increasing in prevalence. They present significant health and economic burdens, and high mortality rates. Antimicrobial catheter lock solutions are an important prophylactic option for preventing fungal CRBSIs. In this study, we compared the effectiveness of two FDA-approved catheter lock solutions (heparin and saline) and three experimental antimicrobial catheter lock solutions—30% citrate, taurolidine-citrate-heparin (TCH), and nitroglycerin-citrate-ethanol (NiCE)—in an in vitro model of catheters colonized by fungi. The fungi tested were five different strains of Candida clinical isolates from cancer patients who contracted CRBSIs. Time-to-biofilm-eradication was assessed in the model with 15, 30, and 60 min exposures to the lock solutions. Only the NiCE lock solution was able to fully eradicate all fungal biofilms within 60 min. Neither 30% citrate nor TCH was able to fully eradicate any of the Candida biofilms in this time frame. The NiCE lock solution was significantly superior to TCH in eradicating biofilms of five different Candida species (p = 0.002 for all). Full article

(This article belongs to the Special Issue Fungal Biofilms)

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Review

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Open AccessReview

Metabolic Interactions between Bacteria and Fungi in Commensal Oral Biofilms

by Marloes Lof, Marleen M. Janus and Bastiaan P. Krom

J. Fungi 2017, 3(3), 40; https://doi.org/10.3390/jof3030040 - 14 Jul 2017

Cited by 30 | Viewed by 11207

Abstract

Oral health is more than just the absence of disease. The key to oral health is a diverse microbiome in an ecological balance. The oral microbiota is one of the most complex and diverse microbial communities in the human body. To maintain oral [...] Read more.

Oral health is more than just the absence of disease. The key to oral health is a diverse microbiome in an ecological balance. The oral microbiota is one of the most complex and diverse microbial communities in the human body. To maintain oral health, balance between the human host and the intrinsic microorganisms is essential. The healthy oral cavity is represented by a great microbial diversity, including both bacteria and fungi. The bacterial microbiome is very well studied. In contrast, fungi inhabiting the oral cavity are often overlooked. All microbial species in the oral cavity form communities which establish a variety of micro-niches and inter- and intra-species interactions. These interactions can be classified into three main groups: physical, chemical and metabolic interactions. Different metabolic interactions are reviewed in this report, among which are the metabolism of sugars, carbon, lactate and oxygen. This review set out with the aim of assessing the importance of metabolic interactions between fungi and bacteria in the healthy oral cavity. Full article

(This article belongs to the Special Issue Fungal Biofilms)

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Open AccessReview

Fungal Biofilms and Polymicrobial Diseases

by Caroline B. Costa-Orlandi, Janaina C. O. Sardi, Nayla S. Pitangui, Haroldo C. De Oliveira, Liliana Scorzoni, Mariana C. Galeane, Kaila P. Medina-Alarcón, Wanessa C. M. A. Melo, Mônica Y. Marcelino, Jaqueline D. Braz, Ana Marisa Fusco-Almeida and Maria José S. Mendes-Giannini

J. Fungi 2017, 3(2), 22; https://doi.org/10.3390/jof3020022 - 10 May 2017

Cited by 144 | Viewed by 11183

Abstract

Biofilm formation is an important virulence factor for pathogenic fungi. Both yeasts and filamentous fungi can adhere to biotic and abiotic surfaces, developing into highly organized communities that are resistant to antimicrobials and environmental conditions. In recent years, new genera of fungi have [...] Read more.

Biofilm formation is an important virulence factor for pathogenic fungi. Both yeasts and filamentous fungi can adhere to biotic and abiotic surfaces, developing into highly organized communities that are resistant to antimicrobials and environmental conditions. In recent years, new genera of fungi have been correlated with biofilm formation. However, Candida biofilms remain the most widely studied from the morphological and molecular perspectives. Biofilms formed by yeast and filamentous fungi present differences, and studies of polymicrobial communities have become increasingly important. A key feature of resistance is the extracellular matrix, which covers and protects biofilm cells from the surrounding environment. Furthermore, to achieve cell–cell communication, microorganisms secrete quorum-sensing molecules that control their biological activities and behaviors and play a role in fungal resistance and pathogenicity. Several in vitro techniques have been developed to study fungal biofilms, from colorimetric methods to omics approaches that aim to identify new therapeutic strategies by developing new compounds to combat these microbial communities as well as new diagnostic tools to identify these complex formations in vivo. In this review, recent advances related to pathogenic fungal biofilms are addressed. Full article

(This article belongs to the Special Issue Fungal Biofilms)

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901 KiB

Open AccessReview

The Candida albicans Biofilm Matrix: Composition, Structure and Function

by Christopher G. Pierce, Taissa Vila, Jesus A. Romo, Daniel Montelongo-Jauregui, Gina Wall, Anand Ramasubramanian and Jose L. Lopez-Ribot

J. Fungi 2017, 3(1), 14; https://doi.org/10.3390/jof3010014 - 08 Mar 2017

Cited by 107 | Viewed by 10476

Abstract

A majority of infections caused by Candida albicans—the most frequent fungal pathogen—are associated with biofilm formation. A salient feature of C. albicans biofilms is the presence of the biofilm matrix. This matrix is composed of exopolymeric materials secreted by sessile cells within [...] Read more.

A majority of infections caused by Candida albicans—the most frequent fungal pathogen—are associated with biofilm formation. A salient feature of C. albicans biofilms is the presence of the biofilm matrix. This matrix is composed of exopolymeric materials secreted by sessile cells within the biofilm, in which all classes of macromolecules are represented, and provides protection against environmental challenges. In this review, we summarize the knowledge accumulated during the last two decades on the composition, structure, and function of the C. albicans biofilm matrix. Knowledge of the matrix components, its structure, and function will help pave the way to novel strategies to combat C. albicans biofilm infections. Full article

(This article belongs to the Special Issue Fungal Biofilms)

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Open AccessReview

Candida glabrata Biofilms: How Far Have We Come?

by Célia F. Rodrigues, Maria Elisa Rodrigues, Sónia Silva and Mariana Henriques

J. Fungi 2017, 3(1), 11; https://doi.org/10.3390/jof3010011 - 01 Mar 2017

Cited by 77 | Viewed by 11947

Abstract

Infections caused by Candida species have been increasing in the last decades and can result in local or systemic infections, with high morbidity and mortality. After Candida albicans, Candida glabrata is one of the most prevalent pathogenic fungi in humans. In addition [...] Read more.

Infections caused by Candida species have been increasing in the last decades and can result in local or systemic infections, with high morbidity and mortality. After Candida albicans, Candida glabrata is one of the most prevalent pathogenic fungi in humans. In addition to the high antifungal drugs resistance and inability to form hyphae or secret hydrolases, C. glabrata retain many virulence factors that contribute to its extreme aggressiveness and result in a low therapeutic response and serious recurrent candidiasis, particularly biofilm formation ability. For their extraordinary organization, especially regarding the complex structure of the matrix, biofilms are very resistant to antifungal treatments. Thus, new approaches to the treatment of C. glabrata’s biofilms are emerging. In this article, the knowledge available on C. glabrata’s resistance will be highlighted, with a special focus on biofilms, as well as new therapeutic alternatives to control them. Full article

(This article belongs to the Special Issue Fungal Biofilms)

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Open AccessReview

The Crucial Role of Biofilms in Cryptococcus neoformans Survival within Macrophages and Colonization of the Central Nervous System

by Lilit Aslanyan, David A. Sanchez, Silvana Valdebenito, Eliseo A. Eugenin, Raddy L. Ramos and Luis R. Martinez

J. Fungi 2017, 3(1), 10; https://doi.org/10.3390/jof3010010 - 24 Feb 2017

Cited by 30 | Viewed by 7302

Abstract

Cryptococcus neoformans is an encapsulated yeast-like fungus capable of causing life threatening meningoencephalitis in patients with impaired immunity. This microbe primarily infects the host via inhalation but has the ability to disseminate to the central nervous system (CNS) either as a single cell [...] Read more.

Cryptococcus neoformans is an encapsulated yeast-like fungus capable of causing life threatening meningoencephalitis in patients with impaired immunity. This microbe primarily infects the host via inhalation but has the ability to disseminate to the central nervous system (CNS) either as a single cell or inside of macrophages. Upon traversing the blood brain barrier, C. neoformans has the capacity to form biofilm-like structures known as cryptococcomas. Hence, we will discuss the C. neoformans elements contributing to biofilm formation including the fungus’ ability to survive in the acidic environment of a macrophage phagosome and inside of the CNS. The purpose of this mini-review is to instill fresh interest in understanding the importance of biofilms on fungal pathogenesis. Full article

(This article belongs to the Special Issue Fungal Biofilms)

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Open AccessReview

Candida Species Biofilms’ Antifungal Resistance

by Sónia Silva, Célia F. Rodrigues, Daniela Araújo, Maria Elisa Rodrigues and Mariana Henriques

J. Fungi 2017, 3(1), 8; https://doi.org/10.3390/jof3010008 - 21 Feb 2017

Cited by 176 | Viewed by 12204

Abstract

Candida infections (candidiasis) are the most prevalent opportunistic fungal infection on humans and, as such, a major public health problem. In recent decades, candidiasis has been associated to Candida species other than Candida albicans. Moreover, biofilms have been considered the most prevalent [...] Read more.

Candida infections (candidiasis) are the most prevalent opportunistic fungal infection on humans and, as such, a major public health problem. In recent decades, candidiasis has been associated to Candida species other than Candida albicans. Moreover, biofilms have been considered the most prevalent growth form of Candida cells and a strong causative agent of the intensification of antifungal resistance. As yet, no specific resistance factor has been identified as the sole responsible for the increased recalcitrance to antifungal agents exhibited by biofilms. Instead, biofilm antifungal resistance is a complex multifactorial phenomenon, which still remains to be fully elucidated and understood. The different mechanisms, which may be responsible for the intrinsic resistance of Candida species biofilms, include the high density of cells within the biofilm, the growth and nutrient limitation, the effects of the biofilm matrix, the presence of persister cells, the antifungal resistance gene expression and the increase of sterols on the membrane of biofilm cells. Thus, this review intends to provide information on the recent advances about Candida species biofilm antifungal resistance and its implication on intensification of the candidiasis. Full article

(This article belongs to the Special Issue Fungal Biofilms)

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