scholarly journals CandidaInfections, Causes, Targets, and Resistance Mechanisms: Traditional and Alternative Antifungal Agents

2013 ◽  
Vol 2013 ◽  
pp. 1-13 ◽  
Author(s):  
Claudia Spampinato ◽  
Darío Leonardi
Keyword(s):  
Antifungal Agents ◽  
Fungal Infections ◽  
Current Knowledge ◽  
Resistance Mechanisms ◽  
Antifungal Drugs ◽  
Diagnostic Methods ◽  
Opportunistic Pathogens ◽  
Yeast Infection ◽  
Life Threatening ◽  
Therapeutic Alternatives

The genusCandidaincludes about 200 different species, but only a few species are human opportunistic pathogens and cause infections when the host becomes debilitated or immunocompromised.Candidainfections can be superficial or invasive. Superficial infections often affect the skin or mucous membranes and can be treated successfully with topical antifungal drugs. However, invasive fungal infections are often life-threatening, probably due to inefficient diagnostic methods and inappropriate initial antifungal therapies. Here, we briefly review our current knowledge of pathogenic species of the genusCandidaand yeast infection causes and then focus on current antifungal drugs and resistance mechanisms. An overview of new therapeutic alternatives for the treatment ofCandidainfections is also provided.

scholarly journals Evolutionary Emergence of Drug Resistance in Candida Opportunistic Pathogens

Genes ◽  
2018 ◽  
Vol 9 (9) ◽  
pp. 461 ◽  
Author(s):  
Ewa Ksiezopolska ◽  
Toni Gabaldón
Keyword(s):  
Drug Resistance ◽  
Fungal Infections ◽  
Current Knowledge ◽  
Treatment Options ◽  
Treatment Strategies ◽  
Developed Countries ◽  
Antifungal Drugs ◽  
Opportunistic Pathogens ◽  
Evolutionary Mechanisms

Fungal infections, such as candidiasis caused by Candida, pose a problem of growing medical concern. In developed countries, the incidence of Candida infections is increasing due to the higher survival of susceptible populations, such as immunocompromised patients or the elderly. Existing treatment options are limited to few antifungal drug families with efficacies that vary depending on the infecting species. In this context, the emergence and spread of resistant Candida isolates are being increasingly reported. Understanding how resistance can evolve within naturally susceptible species is key to developing novel, more effective treatment strategies. However, in contrast to the situation of antibiotic resistance in bacteria, few studies have focused on the evolutionary mechanisms leading to drug resistance in fungal species. In this review, we will survey and discuss current knowledge on the genetic bases of resistance to antifungal drugs in Candida opportunistic pathogens. We will do so from an evolutionary genomics perspective, focusing on the possible evolutionary paths that may lead to the emergence and selection of the resistant phenotype. Finally, we will discuss the potential of future studies enabled by current developments in sequencing technologies, in vitro evolution approaches, and the analysis of serial clinical isolates.

scholarly journals An Overview on Conventional and Non-Conventional Therapeutic Approaches for the Treatment of Candidiasis and Underlying Resistance Mechanisms in Clinical Strains

2020 ◽  
Vol 6 (1) ◽  
pp. 23 ◽  
Author(s):  
Sara B. Salazar ◽  
Rita S. Simões ◽  
Nuno A. Pedro ◽  
Maria Joana Pinheiro ◽  
Maria Fernanda N. N. Carvalho ◽  
...  
Keyword(s):  
Candida Species ◽  
Fungal Infections ◽  
Resistance Mechanisms ◽  
Antifungal Drugs ◽  
Mortality And Morbidity ◽  
Synthetic Chemicals ◽  
Mucosal Surfaces ◽  
Life Threatening ◽  
Resistant Strains ◽  
Novel Approaches

Fungal infections and, in particular, those caused by species of the Candida genus, are growing at an alarming rate and have high associated rates of mortality and morbidity. These infections, generally referred as candidiasis, range from common superficial rushes caused by an overgrowth of the yeasts in mucosal surfaces to life-threatening disseminated mycoses. The success of currently used antifungal drugs to treat candidiasis is being endangered by the continuous emergence of resistant strains, specially among non-albicans Candida species. In this review article, the mechanisms of action of currently used antifungals, with emphasis on the mechanisms of resistance reported in clinical isolates, are reviewed. Novel approaches being taken to successfully inhibit growth of pathogenic Candida species, in particular those based on the exploration of natural or synthetic chemicals or on the activity of live probiotics, are also reviewed. It is expected that these novel approaches, either used alone or in combination with traditional antifungals, may contribute to foster the identification of novel anti-Candida therapies.

scholarly journals Carrier-Mediated Drug Uptake in Fungal Pathogens

Genes ◽  
2020 ◽  
Vol 11 (11) ◽  
pp. 1324
Author(s):  
Mónica Galocha ◽  
Inês Vieira Costa ◽  
Miguel Cacho Teixeira
Keyword(s):  
Drug Resistance ◽  
Fungal Pathogens ◽  
Fungal Infections ◽  
Current Knowledge ◽  
Pathogenic Fungi ◽  
Resistance Mechanisms ◽  
Antifungal Drugs ◽  
Major Facilitator Superfamily ◽  
Drug Uptake ◽  
Human Pathogens

Candida, Aspergillus, and Cryptococcus species are the most frequent cause of severe human fungal infections. Clinically relevant antifungal drugs are scarce, and their effectiveness are hampered by the ability of fungal cells to develop drug resistance mechanisms. Drug effectiveness and drug resistance in human pathogens is very often affected by their “transportome”. Many studies have covered a panoply of drug resistance mechanisms that depend on drug efflux pumps belonging to the ATP-Binding Cassette and Major Facilitator Superfamily. However, the study of drug uptake mechanisms has been, to some extent, overlooked in pathogenic fungi. This review focuses on discussing current knowledge on drug uptake systems in fungal pathogens, highlighting the need for further studies on this topic of great importance. The following subjects are covered: (i) drugs imported by known transporter(s) in pathogenic fungi; and (ii) drugs imported by known transporter(s) in the model yeast Saccharomyces cerevisiae or in human parasites, aimed at the identification of their homologs in pathogenic fungi. Besides its contribution to increase the understanding of drug-pathogen interactions, the practical implications of identifying drug importers in human pathogens are discussed, particularly focusing on drug development strategies.

Potential of Nanoparticles in Combating Candida Infections

2019 ◽  
Vol 16 (5) ◽  
pp. 478-491 ◽  
Author(s):  
Faizan Abul Qais ◽  
Mohd Sajjad Ahmad Khan ◽  
Iqbal Ahmad ◽  
Abdullah Safar Althubiani
Keyword(s):  
Targeted Delivery ◽  
Recent Progress ◽  
Antifungal Agents ◽  
Fungal Infections ◽  
Fold Increase ◽  
Antifungal Drugs ◽  
Low Toxicity ◽  
Candida Infections ◽  
Made In

Aims: The aim of this review is to survey the recent progress made in developing the nanoparticles as antifungal agents especially the nano-based formulations being exploited for the management of Candida infections. Discussion: In the last few decades, there has been many-fold increase in fungal infections including candidiasis due to the increased number of immunocompromised patients worldwide. The efficacy of available antifungal drugs is limited due to its associated toxicity and drug resistance in clinical strains. The recent advancements in nanobiotechnology have opened a new hope for the development of novel formulations with enhanced therapeutic efficacy, improved drug delivery and low toxicity. Conclusion: Metal nanoparticles have shown to possess promising in vitro antifungal activities and could be effectively used for enhanced and targeted delivery of conventionally used drugs. The synergistic interaction between nanoparticles and various antifungal agents have also been reported with enhanced antifungal activity.

scholarly journals Reinforcing the Immunocompromised Host Defense against Fungi: Progress beyond the Current State of the Art

2021 ◽  
Vol 7 (6) ◽  
pp. 451
Author(s):  
Georgios Karavalakis ◽  
Evangelia Yannaki ◽  
Anastasia Papadopoulou
Keyword(s):  
Host Defense ◽  
Hematopoietic Cell Transplantation ◽  
State Of The Art ◽  
Fungal Infections ◽  
Solid Organ Transplantation ◽  
Immunocompromised Host ◽  
Antifungal Drugs ◽  
Solid Organ ◽  
Cell Immunotherapy ◽  
Life Threatening

Despite the availability of a variety of antifungal drugs, opportunistic fungal infections still remain life-threatening for immunocompromised patients, such as those undergoing allogeneic hematopoietic cell transplantation or solid organ transplantation. Suboptimal efficacy, toxicity, development of resistant variants and recurrent episodes are limitations associated with current antifungal drug therapy. Adjunctive immunotherapies reinforcing the host defense against fungi and aiding in clearance of opportunistic pathogens are continuously gaining ground in this battle. Here, we review alternative approaches for the management of fungal infections going beyond the state of the art and placing an emphasis on fungus-specific T cell immunotherapy. Harnessing the power of T cells in the form of adoptive immunotherapy represents the strenuous protagonist of the current immunotherapeutic approaches towards combating invasive fungal infections. The progress that has been made over the last years in this field and remaining challenges as well, will be discussed.

scholarly journals Do Mast Cells Contribute to the Antifungal Host Defense?

Cells ◽  
2021 ◽  
Vol 10 (10) ◽  
pp. 2510
Author(s):  
Paulina Żelechowska ◽  
Joanna Pastwińska ◽  
Ewa Brzezińska-Błaszczyk ◽  
Justyna Agier
Keyword(s):  
Mast Cells ◽  
Host Defense ◽  
Immune Cells ◽  
Defense Mechanisms ◽  
Fungal Infections ◽  
Current Knowledge ◽  
Extracellular Dna ◽  
Opportunistic Pathogens ◽  
Strategic Location ◽  
Fungal Kingdom

The fungal kingdom includes a group of microorganisms that are widely distributed in the environment, and therefore the exposure to them is almost constant. Furthermore, fungal components of the microbiome, i.e., mycobiome, could serve as a reservoir of potentially opportunistic pathogens. Despite close encounters with fungi, defense mechanisms that develop during fungal infections remain unexplored. The strategic location of mast cells (MCs) close to the external environment places them among the first cells to encounter pathogens along with the other innate immune cells. MCs are directly involved in the host defense through the ability to destroy pathogens or indirectly by activating other immune cells. Most available data present MCs’ involvement in antibacterial, antiviral, or antiparasitic defense mechanisms. However, less is known about their contribution in defense mechanisms against fungi. MCs may support immune responses to fungi or their specific molecules through initiated degranulation, synthesis and release of cytokines, chemokines, mediators, and generation of reactive oxygen species (ROS), as well as immune cells’ recruitment, phagocytosis, or provision of extracellular DNA traps. This review summarizes current knowledge on host defense mechanisms against fungi and MCs’ involvement in those processes. It also describes the effects of fungi or fungus-derived constituents on MCs’ activity.

scholarly journals Acylhydrazones as Antifungal Agents Targeting the Synthesis of Fungal Sphingolipids

2018 ◽  
Vol 62 (5) ◽  
Author(s):  
Cristina Lazzarini ◽  
Krupanandan Haranahalli ◽  
Robert Rieger ◽  
Hari Krishna Ananthula ◽  
Pankaj B. Desai ◽  
...  
Keyword(s):  
Mammalian Cells ◽  
Antifungal Agents ◽  
Fungal Infections ◽  
Antifungal Drugs ◽  
Fungal Resistance ◽  
Content Type ◽  
Highly Active ◽  
Pharmacokinetic Properties ◽  
Pass Through

ABSTRACTThe incidence of invasive fungal infections has risen dramatically in recent decades. Current antifungal drugs are either toxic, likely to interact with other drugs, have a narrow spectrum of activity, or induce fungal resistance. Hence, there is a great need for new antifungals, possibly with novel mechanisms of action. Previously our group reported an acylhydrazone called BHBM that targeted the sphingolipid pathway and showed strong antifungal activity against several fungi. In this study, we screened 19 derivatives of BHBM. Three out of 19 derivatives were highly active againstCryptococcus neoformansin vitroand had low toxicity in mammalian cells. In particular, one of them, called D13, had a high selectivity index and showed better activity in an animal model of cryptococcosis, candidiasis, and pulmonary aspergillosis. D13 also displayed suitable pharmacokinetic properties and was able to pass through the blood-brain barrier. These results suggest that acylhydrazones are promising molecules for the research and development of new antifungal agents.

scholarly journals The importance of rapid diagnosis for multidrug-resistant Candida: an interview with Maurizio Sanguinetti

2019 ◽  
Vol 14 (12) ◽  
pp. 1011-1012
Author(s):  
Maurizio Sanguinetti
Keyword(s):  
Infectious Diseases ◽  
Fungal Pathogens ◽  
Fungal Infections ◽  
Resistance Mechanisms ◽  
Rapid Diagnosis ◽  
Antifungal Drugs ◽  
Full Professor ◽  
Research Activity ◽  
Diagnostic Strategies ◽  
Personalized Care

In this exclusive interview, Maurizio Sanguinetti discusses current issues with Candida fungal infection diagnoses, in light of its rising resistance to antifungal drugs. This interview was conducted by Ellen Colvin, Editor of Future Microbiology. Maurizio Sanguinetti, MD, is full Professor of Microbiology at the Università Cattolica del Sacro Cuore of Rome, Italy, and Director of the Institute of Microbiology and Chief of the Department of Laboratory Sciences and Infectious Diseases Sciences at the Fondazione Policlinico Agostino Gemelli IRCCS of Rome, Italy. For several years, the research activity of Maurizio Sanguinetti has mainly focused on the development of molecular methods for the rapid diagnosis of bacterial, mycobacterial and fungal infections; the elucidation of virulence and antimicrobial resistance mechanisms in clinically relevant bacterial and fungal pathogens; the characterization of the human microbiota in relationship to infectious and noninfectious diseases and implementation of new diagnostic strategies for the personalized care of patients with infectious diseases.

scholarly journals Antifungal Resistance Regarding Malassezia pachydermatis: Where Are We Now?

2020 ◽  
Vol 6 (2) ◽  
pp. 93
Author(s):  
Andrea Peano ◽  
Elizabeth Johnson ◽  
Elisa Chiavassa ◽  
Paolo Tizzani ◽  
Jacques Guillot ◽  
...  
Keyword(s):  
Treatment Failure ◽  
Antifungal Agents ◽  
Standard Procedure ◽  
Resistance Mechanisms ◽  
Antifungal Resistance ◽  
Antifungal Drugs ◽  
Malassezia Pachydermatis ◽  
Development Of Resistance ◽  
Ear Canals

Malassezia pachydermatis is a yeast inhabiting the skin and ear canals in healthy dogs. In the presence of various predisposing conditions it can cause otitis and dermatitis, which are treated with multiple antifungal agents, mainly azole derivatives. This manuscript aims to review the available evidence regarding the occurrence of resistance phenomena in this organism. Various findings support the capacity of M. pachydermatis for developing resistance. These include some reports of treatment failure in dogs, the reduced antifungal activity found against yeast isolates sampled from dogs with exposure to antifungal drugs and strains exposed to antifungal agents in vitro, and the description of resistance mechanisms. At the same time, the data reviewed may suggest that the development of resistance is a rare eventuality in canine practice. For example, only three publications describe confirmed cases of treatment failure due to antifungal resistance, and most claims of resistance made by past studies are based on interpretive breakpoints that lack sound support from the clinical perspective. However, it is possible that resistant cases are underreported in literature, perhaps due to the difficulty of obtaining a laboratory confirmation given that a standard procedure for susceptibility testing of M. pachydermatis is still unavailable. These considerations highlight the need for maintaining surveillance for the possible emergence of clinically relevant resistance, hopefully through a shared strategy put in place by the scientific community.

Antibiofilm activity of antifungal drugs, including the novel drug olorofim, against Lomentospora prolificans

2020 ◽  
Author(s):  
Lisa Kirchhoff ◽  
Silke Dittmer ◽  
Ann-Kathrin Weisner ◽  
Jan Buer ◽  
Peter-Michael Rath ◽  
...  
Keyword(s):  
Amphotericin B ◽  
Biofilm Formation ◽  
Laser Scanning ◽  
Antifungal Agents ◽  
Fungal Infections ◽  
Pathogenic Fungus ◽  
Antifungal Drugs ◽  
Laser Scanning Microscopy ◽  
Confocal Laser ◽  
Antibiofilm Activity

Abstract Objectives Patients with immunodeficiency or cystic fibrosis frequently suffer from respiratory fungal infections. In particular, biofilm-associated fungi cause refractory infection manifestations, linked to increased resistance to anti-infective agents. One emerging filamentous fungus is Lomentospora prolificans. Here, the biofilm-formation capabilities of L. prolificans isolates were investigated and the susceptibility of biofilms to various antifungal agents was analysed. Methods Biofilm formation of L. prolificans (n = 11) was estimated by crystal violet stain and antibiofilm activity was additionally determined via detection of metabolically active biofilm using an XTT assay. Amphotericin B, micafungin, voriconazole and olorofim were compared with regard to their antibiofilm effects when added prior to adhesion, after adhesion and on mature and preformed fungal biofilms. Imaging via confocal laser scanning microscopy was carried out to demonstrate the effect of drug treatment on the fungal biofilm. Results Antibiofilm activities of the tested antifungal agents were shown to be most effective on adherent cells whilst mature biofilm was the most resistant. The most promising antibiofilm effects were detected with voriconazole and olorofim. Olorofim showed an average minimum biofilm eradication concentration (MBEC) of 0.06 mg/L, when added prior to and after adhesion. The MBECs of voriconazole were ≤4 mg/L. On mature biofilm the MBECs of olorofim and voriconazole were higher than the previously determined MICs against planktonic cultures. In contrast, amphotericin B and especially micafungin did not exhibit sufficient antibiofilm activity against L. prolificans. Conclusions To our knowledge, this is the first study demonstrating the antibiofilm potential of olorofim against the human pathogenic fungus L. prolificans.

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