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1.
Braz. j. biol ; 84: e255080, 2024. tab, graf
Artigo em Inglês | LILACS-Express | MEDLINE, LILACSEXPRESS, LILACS, VETINDEX | ID: biblio-1364503

RESUMO

Abstract In the current context of emerging drug-resistant fungal pathogens such as Candida albicans and Candida parapsilosis, discovery of new antifungal agents is an urgent matter. This research aimed to evaluate the antifungal potential of 2-chloro-N-phenylacetamide against fluconazole-resistant clinical strains of C. albicans and C. parapsilosis. The antifungal activity of 2-chloro-N-phenylacetamide was evaluated in vitro by the determination of the minimum inhibitory concentration (MIC), minimum fungicidal concentration (MFC), inhibition of biofilm formation and its rupture, sorbitol and ergosterol assays, and association between this molecule and common antifungal drugs, amphotericin B and fluconazole. The test product inhibited all strains of C. albicans and C. parapsilosis, with a MIC ranging from 128 to 256 µg.mL-1, and a MFC of 512-1,024 µg.mL-1. It also inhibited up to 92% of biofilm formation and rupture of up to 87% of preformed biofilm. 2-chloro-N-phenylacetamide did not promote antifungal activity through binding to cellular membrane ergosterol nor it damages the fungal cell wall. Antagonism was observed when combining this substance with amphotericin B and fluconazole. The substance exhibited significant antifungal activity by inhibiting both planktonic cells and biofilm of fluconazole-resistant strains. Its combination with other antifungals should be avoided and its mechanism of action remains to be established.


Resumo No atual contexto de patógenos fúngicos resistentes emergentes tais como Candida albicans e Candida parapsilosis, a descoberta de novos agentes antifúngicos é uma questão urgente. Esta pesquisa teve como objetivo avaliar o potencial antifúngico da 2-cloro-N-fenilacetamida contra cepas clínicas de C. albicans e C. parapsilosis resistentes a fluconazol. A atividade antifúngica da substância foi avaliada in vitro através da determinação da concentração inibitória mínima (CIM), concentração fungicida mínima (CFM), ruptura e inibição da formação de biofilme, ensaios de sorbitol e ergosterol, e associação entre esta molécula e antifúngicos comuns, anfotericina B e fluconazol. O produto teste inibiu todas as cepas de C. albicans e C. parapsilosis, com uma CIM variando de 128 a 256 µg.mL-1, e uma CFM de 512-1,024 µg.mL-1. Também inibiu até 92% da formação de biofilme e causou a ruptura de até 87% de biofilme pré-formado. A 2-cloro-N-fenilacetamida não promoveu atividade antifúngica pela ligação ao ergosterol da membrana celular fúngica, tampouco danificou a parede celular. Antagonismo foi observado ao combinar esta substância com anfotericina B e fluconazol. A substância exibiu atividade antifúngica significativa ao inibir tanto as células planctônicas quanto o biofilme das cepas resistentes ao fluconazol. Sua combinação com outros antifúngicos deve ser evitada e seu mecanismo de ação deve ser estabelecido.

2.
J Mycol Med ; 32(4): 101302, 2022 Jun 09.
Artigo em Inglês | MEDLINE | ID: mdl-35717682

RESUMO

INTRODUCTION: Vaginal infections are one of the most common reason for gynecological consultations. Many of them are the result of overgrowth of resident microorganisms. The clinical symptoms of vulvovaginal candidiasis are nonspecific and an accurate diagnosis is a problem that often leads to inadequate treatment or delays in treatment. The lack of an exact and practical diagnostic method is a common cause of misdiagnosis. AIM: To create a complex, quantitative method for the diagnosis of vulvovaginal candidiasis which to enables differentiation from vaginal fungal colonization. MATERIAL AND METHODS: A total of 2306 vaginal samples were examined. Clinical, microbiological, epidemiological methods and statistical models are used. RESULTS AND DISCUSSION: The proposed score system is a specific, sensitive and inexpensive method to routinely diagnose vulvovaginal candidiasis. Statistical processing of the obtained data shows the impact of the individual components on which the method is based: the presence of vaginal discharge, pruritus, direct microscopy and assessment of the fungal growth. The data analysis reveals good sensitivity (71%) and high specificity (98%) of the method. This allows accurate interpretation of the result of the clinical and microbiological examination of each patient. CONCLUSION: The system for diagnosing vulvovaginal candidiasis is complex and based on quantitative indicators. The method can be used to differentiate vulvovaginal candidiasis from vaginal fungal colonization (the cut-off value is 5.5 points) and to more accurately interpret a Candida positive result from quantitative real-time PCR in asymptomatic patients or in women with mixed vaginal infection.

3.
Future Microbiol ; 2022 Jun 24.
Artigo em Inglês | MEDLINE | ID: mdl-35748170

RESUMO

Candida nivariensis caused refractory esophagitis in a 36-year-old Brazilian man coinfected with HIV and Leishmania. A literature review on this rare fungal pathogen is also presented. The diagnosis was made, and pathogen identification was performed using matrix-assisted laser desorption ionization-time of flight mass spectrometry and sequencing of the LSU/26S region. An antifungigram was performed using broth microdilution. A literature search of PubMed was performed. The causative agent, C. nivariensis, was resistant to fluconazole and voriconazole. The patient's condition worsened considerably, and he passed away. This is the second report of this Candida species in Brazil and the first case reported worldwide of refractory esophagitis in a patient coinfected with HIV and Leishmania. The case illustrates the importance of precise identification and antifungal susceptibility testing when isolating this emerging pathogen.

4.
Front Cell Infect Microbiol ; 12: 895068, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35646731

RESUMO

Candida albicans Als1 is a large cell-surface glycoprotein most often discussed for its role in mediating ligand-binding and aggregative interactions. Relative to a wild-type control, deletion of ALS1 produced a strain that showed delayed germ-tube formation and delayed disease progression in a murine model of disseminated candidiasis. Populations of Δals1/Δals1 cultured cells had a higher proportion of smaller cells compared to wild-type or ALS1 reintegrant control cultures. The goal of this work was to investigate whether this difference in cell-size distributions was responsible for delayed germ-tube formation and delayed disease progression. Flow cytometry was used to select populations of wild-type and Δals1/Δals1 cells with varied cell-size distributions. Delayed germ-tube formation was demonstrated for small cells sorted from a wild-type (ALS1/ALS1) culture population. Large cells sorted from a Δals1/Δals1 culture formed germ tubes as quickly as the wild-type control demonstrating clearly that the Δals1/Δals1 germ-tube formation delays were attributable to cell size. In vivo, smaller-sized cells of the wild-type control showed fewer colony-forming units (cfu) per gram of kidney tissue and less-severe histopathology lesions compared to larger cells of the same strain. The Δals1/Δals1 strain showed reduced cfu/g of kidney tissue and less-severe lesions compared to the wild-type control. However, isolation and testing of the larger cells from the Δals1/Δals1 population increased cfu/g of tissue and showed increased lesion severity compared to the overall mutant cell population. In vivo hypha lengths from the large, sorted Δals1/Δals1 cells were comparable to those for the wild-type control strain. These results demonstrated that a large share of the Δals1/Δals1 in-vivo phenotype was attributable to cell size. Collectively, the data suggest a role for Als1 in C. albicans cell size homeostasis, a novel hypothesis for further exploration.


Assuntos
Candida albicans , Candidíase , Esclerose Amiotrófica Lateral , Animais , Candida albicans/genética , Progressão da Doença , Proteínas Fúngicas/genética , Hifas , Camundongos
5.
Fungal Biol ; 126(6-7): 407-420, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35667828

RESUMO

Flavonoids are a diverse group of compounds originating from several natural plant sources. Various biological effects of flavonoids have been reported, including antimicrobial and antifungal activities. In this study, we showed the possibility of using commercial flavonoids, i.e. baicalein and quercetin, based on natural equivalents as compounds with antifungal properties against Candida albicans species. The effects of baicalein and/or quercetin were investigated using reference C. albicans strain and 50 clinical strains isolated from vulvovaginal candidiasis (VVC) patients. Baicalein and quercetin MIC values against C. albicans strains ranged between 0.5 and 256 µg/ml. We observed predominantly indifferent, synergistic, or partially synergistic interactions between both flavonoids and between the flavonoids and fluconazole in the treatment of planktonic cells of the C. albicans strains. Treatment with the flavonoid complex inhibited adhesion and aggregation of cells, cell surface hydrophobicity (CSH), flocculation, biofilm formation and reduced hyphal growth. Real-time RT-PCR revealed that baicalein and quercetin in combination down-regulated the expression of biofilm-specific genes. Finally, we observed increase in the cell membrane permeability of C. albicans and its physical destruction as a result of the synergistic activity of baicalein and quercetin. Our research evidences the effectiveness of baicalein and quercetin applied in combination as potential anti-Candida agents.


Assuntos
Antifúngicos , Candida albicans , Antifúngicos/farmacologia , Biofilmes , Candida , Feminino , Flavanonas , Flavonoides/farmacologia , Genitália Feminina , Humanos , Testes de Sensibilidade Microbiana , Quercetina/farmacologia
6.
Int J Antimicrob Agents ; : 106614, 2022 Jun 09.
Artigo em Inglês | MEDLINE | ID: mdl-35691603

RESUMO

AIM: Invasive candidiasis is the main fungal infection in patients attending health services and is associated with high mortality rates and prolonged hospital stay. We aimed to comparatively evaluate the efficacy and safety of antifungal agents for treating candidemia. METHODS: A systematic review with network meta-analysis (NMA), surface under the cumulative ranking analysis (SUCRA) and stochastic multicriteria acceptability analyses (SMAA) were performed (PROSPERO-CRD42020149264). Searches were conducted in PubMed and Scopus (Nov-2021). Randomised controlled trials evaluating the effect of oral antifungals (any dose or regimen) on mycological cure, discontinuation rates and adverse events were included. RESULTS: Overall, 13 trials (n=3,632) were analysed. No significant differences among therapies were found for the efficacy outcomes; however, caspofungin (50-150 mg), rezafungin (200-400mg) and micafungin (100-150 mg) were considered the most promising therapies, leading to higher rates of both clinical and mycological responses (SUCRA overall response over 60%). Fluconazole (400 mg) was rated as the last option for overall response (17%). Rezafungin (200-400mg) and micafungin (100 mg) were associated with lower discontinuation rates (<40%); conventional amphotericin B (0.6-0.7mg/kg) was more likely to be discontinued (OR 0.08 [95% CrI 0.00-0.95] vs. caspofungin 150 mg) and may impair liver function (87%). CONCLUSION: Echinocandins should be listed as first-line treatments for invasive candidiasis following a priority order of caspofungin and micafungin. Rezafungin, an under development echinocandin, represents a potential option that should be further investigated. Azoles and liposomal amphotericin B can be used as second-line treatments in cases of fungal resistance or hypersensitivity.

7.
Front Microbiol ; 13: 787119, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35694318

RESUMO

"Unity in strength" is a notion that can be exploited to characterize biofilms as they bestow microbes with protection to live freely, escalate their virulence, confer high resistance to therapeutic agents, and provide active grounds for the production of biofilms after dispersal. Naturally, fungal biofilms are inherently resistant to many conventional antifungals, possibly owing to virulence factors as their ammunitions that persistently express amid planktonic transition to matured biofilm state. These ammunitions include the ability to form polymicrobial biofilms, emergence of persister cells post-antifungal treatment and acquisition of resistance genes. One of the major disorders affecting vaginal health is vulvovaginal candidiasis (VVC) and its reoccurrence is termed recurrent VVC (RVVC). It is caused by the Candida species which include Candida albicans and Candida glabrata. The aforementioned Candida species, notably C. albicans is a biofilm producing pathogen and habitually forms part of the vaginal microbiota of healthy women. Latest research has implicated the role of fungal biofilms in VVC, particularly in the setting of treatment failure and RVVC. Consequently, a plethora of studies have advocated the utilization of probiotics in addressing these infections. Specifically, the excreted or released compounds of probiotics which are also known as postbiotics are being actively researched with vast potential to be used as therapeutic options for the treatment and prevention of VVC and RVVC. These potential sources of postbiotics are harnessed due to their proven antifungal and antibiofilm. Hence, this review discusses the role of Candida biofilm formation in VVC and RVVC. In addition, we discuss the application of pro-, pre-, post-, and synbiotics either individually or in combined regimen to counteract the abovementioned problems. A clear understanding of the role of biofilms in VVC and RVVC will provide proper footing for further research in devising novel remedies for prevention and treatment of vaginal fungal infections.

9.
Front Cell Infect Microbiol ; 12: 879237, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35734578

RESUMO

Currently, non-albicans Candida species, including C. tropicalis, C. glabrata, and C. parapsilosis, are becoming an increasing epidemiological threat, predominantly due to the distinct collection of virulence mechanisms, as well as emerging resistance to antifungal drugs typically used in the treatment of candidiasis. They can produce biofilms that release extracellular vesicles (EVs), which are nanometric spherical structures surrounded by a lipid bilayer, transporting diversified biologically active cargo, that may be involved in intercellular communication, biofilm matrix production, and interaction with the host. In this work, we characterize the size and protein composition of these structures for three species of non-albicans Candida fungi forming biofilm, indicating considerable heterogeneity of the investigated population of fungal EVs. Examination of the influence of EVs on cytokine production by the human monocytic cell line THP-1 differentiated into macrophage-like cells revealed that the tested vesicles have a stimulating effect on the secretion of tumor necrosis factor α and interleukin 8, while they reduce the production of interleukin 10. This may indicate the proinflammatory nature of the effect of EVs produced by these species on the host immune cells. Moreover, it has been indicated that vesicles may be involved in C. tropicalis biofilm resistance to fluconazole and caspofungin. This reveals the important role of EVs not only in the physiology of C. tropicalis, C. glabrata, and C. parapsilosis fungi but also in the pathogenesis of infections associated with the production of fungal biofilm.


Assuntos
Candida glabrata , Vesículas Extracelulares , Antifúngicos/farmacologia , Biofilmes , Candida , Candida parapsilosis , Candida tropicalis , Humanos , Testes de Sensibilidade Microbiana
10.
J Pharm Pract ; : 8971900221108716, 2022 Jun 15.
Artigo em Inglês | MEDLINE | ID: mdl-35705106

RESUMO

The high morbidity and mortality rates associated with invasive fungal infections have led to the overutilization of empiric antifungal therapies. With increasing antibiotic resistance, the careful consideration of prophylactic or empiric antifungal use is critical. The purpose of this review is to evaluate the available literature regarding the current practice of utilizing antifungal agents for intra-abdominal infections based on specific surgical procedures and patient risk factors. Relevant articles were identified through a comprehensive literature search of several databases using the keywords antifungal agents, postoperative period, preoperative care, surgical procedures, and intra-abdominal infections. Only articles that evaluated the use of empiric antifungals for suspected or confirmed intra-abdominal infections and surgical procedures were included in this review. Based on the available literature, antifungal prophylaxis is appropriate in patients who meet the criteria for high-risk invasive candidiasis, kidney or liver transplant recipients, severely-immunocompromised patients with perforated peptic ulcer, peritonitis, and patients on peritoneal dialysis who are failing on a therapeutic antibiotic regimen. We acknowledge that the evidence for using antifungal therapy empirically for all surgical procedures is lacking, and the following review is based on available literature and current guidelines.

11.
Antimicrob Agents Chemother ; : e0030822, 2022 Jun 14.
Artigo em Inglês | MEDLINE | ID: mdl-35699443

RESUMO

Candida albicans causes debilitating, often azole-resistant, infections in patients with chronic mucocutaneous candidiasis (CMC). Amphotericin B (AMB) resistance is rare, but AMB use is limited by parenteral administration and nephrotoxicity. In this study, we evaluated cochleated AMB (CAMB), a new oral AMB formulation, in mouse models of oropharyngeal candidiasis (OPC) and vulvovaginal candidiasis (VVC) and in patients with azole-resistant CMC. OPC and VVC were modeled in Act1-/- mice, and mucosal tissue fungal burden was assessed after once-daily treatment with CAMB, vehicle, or AMB-deoxycholate (AMB-d). Four patients with azole-resistant CMC enrolled in a phase 2 CAMB dose-escalation study. The primary endpoint was clinical improvement at 2 weeks followed by optional extension for long-term CMC suppression to assess safety and efficacy. CAMB-treated mice had significantly reduced tongue and vaginal fungal burdens compared to vehicle-treated mice and exhibited comparable fungal burden reduction relative to AMB-d-treated mice. All CAMB-treated patients reached clinical efficacy by 2 weeks, three at 400 mg twice daily and one at 200 mg twice-daily dosing. All patients continued to the extension phase, with three having sustained clinical improvement of OPC and esophageal candidiasis (EC) for up to 60 months. One patient had a relapse of esophageal symptoms at week 24 and was withdrawn from further study. Clinical responses were not seen for onychomycosis or VVC. CAMB was safe and well-tolerated, without any evidence of nephrotoxicity. In summary, oral CAMB reduced tongue and vaginal fungal burdens during murine candidiasis. A proof-of-concept clinical trial in human CMC showed efficacy with good tolerability and safety. This study has been registered at ClinicalTrials.gov under identifier NCT02629419.

12.
Indian J Crit Care Med ; 26(5): 560-563, 2022 May.
Artigo em Inglês | MEDLINE | ID: mdl-35719436

RESUMO

Introduction: Invasive candidiasis is a serious infection seen in hospitalized or immunocompromised patients. Mortality rates for candidemia can be as high as 30-60%. Candida auris is an emerging species of Candida and is increasingly becoming a global public health problem. Methods: This was a retrospective observational study, in which we analyzed 79 episodes of candidemia. Blood cultures were done using the Bactec™ FX blood culturing instrument (Becton, Dickinson and Company Sparks, Maryland, USA). Species identification was done using VITEK® 2 YST panels (bioMérieux Inc., Durham, North Carolina, USA). Antifungal susceptibility testing was performed using VITEK® 2 AST-YSO8 panels (bioMérieux Inc., Durham, North Carolina, USA). Results: Among the 79 episodes, the most common species was found to be C. auris (43.03% of all the episodes). Candida tropicalis was found to be the second most common species in patients admitted to our hospital with candidemia. All the isolates of C. auris were resistant to fluconazole, while 32.35 % of the isolates were also resistant to amphotericin B. Crude mortality in patients with C. auris candidemia was higher than the crude mortality for the other species. Conclusion: This is the first study from India where C. auris was seen as the most predominant species among patients admitted with candidemia. This is a serious issue given the high rates of fluconazole resistance, mortality, and cost of therapy associated with C. auris bloodstream infections. Urgent attention needs to be diverted to infection control practices and antimicrobial stewardship programs. How to cite this article: Prayag PS, Patwardhan S, Panchakshari S, Rajhans PA, Prayag A. The Dominance of Candida auris: A Single-center Experience of 79 Episodes of Candidemia from Western India. Indian J Crit Care Med 2022;26(5):560-563.

13.
Adv Biomed Res ; 11(1): 29, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35722454

RESUMO

Background: Oral candidiasis (OC) has been noticed as a common mucous membrane infection in immunocompromised patients such as that diabetes. This study, focused on the genotyping of Candida albicans and enzymatic activities of Candida species recovered from oral mucosa among diabetes patients and healthy individuals. Materials and Methods: Specimens were obtained from oral mucosa of One-hundred and sixty patients with type 2 diabetic and 108 healthy individuals. All isolates were definitely identified by ribosomal DNA (rDNA) gene sequencinghHydrophobicity, hemolytic activities of Candida species and genotypes of C. albicans were determined through polymerase chain reaction (CA-INT). Results: , Eighty eight (55%) samples out of 160, were positive for Candida species in diabetic patients. Moreover, 79.5% (70/88) and 20.5% (18/88) isolates belonged to the C. albicans and non-albicans Candida species respectively. Three genotypes of C. albicans have recovered in diabetic patients: genotype A (71.42%), B (21.42%), and C (7.14%). In healthy individuals, 42.6% (46/102) Candida species recovered from oral cavity, with the highest prevalence of genotype A (76.6% of C. albicans). Additionally, hydrophobicity and hemolytic activities from Candida species were significantly greater in diabetes patients than healthy nondiabetic subjects. Conclusion: Collectively, C. albicans was the most causative agent isolated from diabetes patients and non-diabetes healthy individuals. Genotype A, as the most remarkable genotype, should be mentioned in both groups. Higher potential hydrophobicity and hemolytic activities of Candida species in diabetic patients compared to healthy cases suggest these features triggering pathogenicity of OC in diabetes patients.

14.
Microorganisms ; 10(6)2022 Jun 13.
Artigo em Inglês | MEDLINE | ID: mdl-35744725

RESUMO

Invasive candidiasis (IC) is a systemic life-threatening infection of immunocompromised humans, but remains a relatively neglected disease among public health authorities. Ongoing assessments of disease epidemiology are needed to identify and map trends of importance that may necessitate improvements in disease management and patient care. Well-established incidence increases, largely due to expanding populations of patients with pre-disposing risk factors, has led to increased clinical use and pressures on antifungal drugs. This has been exacerbated by a lack of fast, accurate diagnostics that have led treatment guidelines to often recommend preventative strategies in the absence of proven infection, resulting in unnecessary antifungal use in many instances. The consequences of this are multifactorial, but a contribution to emerging drug resistance is of primary concern, with high levels of antifungal use heavily implicated in global shifts to more resistant Candida strains. Preserving and expanding the utility and number of antifungals should therefore be of the highest priority. This may be achievable through the development and use of biomarker tests, bringing about a new era in improved antifungal stewardship, as well as novel antifungals that offer favorable profiles by targeting Candida pathogenesis mechanisms over cell viability.

15.
Pathogens ; 11(6)2022 May 25.
Artigo em Inglês | MEDLINE | ID: mdl-35745472

RESUMO

Vulvovaginal candidiasis (VVC) is a prevalent gynaecological disease characterised by vaginal wall inflammation that is caused by Candida species. VVC impacts almost three-quarters of all women throughout their reproductive years. As the vaginal mucosa is the first point of contact with microbes, vaginal epithelial cells are the first line of defence against opportunistic Candida infection by providing a physical barrier and mounting immunological responses. The mechanisms of defence against this infection are displayed through the rapid shedding of epithelial cells, the presence of pattern recognition receptors, and the release of inflammatory cytokines. The bacterial microbiota within the mucosal layer presents another form of defence mechanism within the vagina through acidic pH regulation, the release of antifungal peptides and physiological control against dysbiosis. The significant role of the microbiota in maintaining vaginal health promotes its application as one of the potential treatment modalities against VVC with the hope of alleviating the burden of VVC, especially the recurrent disease. This review discusses and summarises current progress in understanding the role of vaginal mucosa and host immunity upon infection, together with the function of vaginal microbiota in VVC.

16.
Pediatr Dermatol ; 2022 Jun 06.
Artigo em Inglês | MEDLINE | ID: mdl-35668547

RESUMO

Candidal balanitis typically affects sexually active adult males and may present as eroded papules, pustules, whitish discharge or erythema with dry glazed appearance. We report an unusual presentation of this common infection in an uncommon demographic, candidal balanitis presenting as coalescent vesicles and erosions arranged in an arcuate pattern in a pre-school child.

17.
Methods Mol Biol ; 2517: 269-285, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35674962

RESUMO

Candida auris infections present a critical problem to the healthcare system in many parts of the world. This yeast clinically manifests as a disseminated candidiasis which can be life-threating for susceptible individuals, as well as cutaneous and wound infections. Moreover, C. auris can colonize the skin and act as a nidus of infection. Importantly, this emerging yeast unlike other Candida spp. has demonstrated multidrug resistance; thus its eradication can be challenging. Animal models are important to gain insight into the pathogenesis of this infection, as well as play a significant role in drug development. In this chapter, we describe two C. auris animal models: a cutaneous infection guinea pig model and a skin decolonization mouse model.


Assuntos
Candidíase , Animais , Antifúngicos/farmacologia , Antifúngicos/uso terapêutico , Candida , Candidíase/tratamento farmacológico , Modelos Animais de Doenças , Cobaias , Camundongos , Saccharomyces cerevisiae
18.
Methods Mol Biol ; 2517: 317-328, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35674965

RESUMO

With the recent emergence of multidrug-resistant Candida auris, there is an urgent need for new antifungal compounds with novel pharmacodynamic and pharmacokinetic properties that can treat systemic fungal infections caused by this emerging yeast. Historically, testing the efficacy of treatment for disseminated candidiasis was accomplished using a diverse array of in vivo animal models, including mice which offer an advantage both in their similarities to humans and their lower cost of maintenance. However, in order to create effective in vivo models for testing new antifungal compounds designed to treat systemic infections, it is important that these models also mimic several of the relevant predisposing conditions that can lead to disseminated candidiasis. Here, we describe an immunocompromised mouse model of hematogenously disseminated C. auris infection, which may have utility to test the efficacy of candidate antifungal compounds.


Assuntos
Candida , Candidíase Invasiva , Animais , Antifúngicos/farmacologia , Antifúngicos/uso terapêutico , Candidíase , Candidíase Invasiva/tratamento farmacológico , Modelos Animais de Doenças , Camundongos , Testes de Sensibilidade Microbiana
19.
Med Mycol ; 2022 Jun 09.
Artigo em Inglês | MEDLINE | ID: mdl-35679084

RESUMO

Incidence of vulvovaginal candidiasis are strikingly high and treatment options are limited with nearly 50% Candida glabrata cases left untreated or experience treatment failures. The vaginal microenvironment is rich in lactic acid, and the adaptation of C. glabrata to lactic acid (LA) is the main reason for clinical treatment failure. In the present study, C. glabrata and its vaginal clinical isolates were comprehensively investigated for their growth response, metabolic adaptation and altered cellular pathway to LA using different biochemical techniques, metabolic profiling and transcriptional studies. C. glabrata shown considerable variations in its topological and biochemical features without compromising growth in LA media. Chemical profiling data highlighted involvement of cell wall/membrane, ergosterol and oxidative stress related pathways in mediating adaptative response of C. glabrata towards LA. Further, one dimensional proton (1H) NMR spectroscopy based metabolic profiling revealed significant modulation in 19 metabolites of C. glabrata cells upon growth in LA. Interestingly myo-inositol, xylose, putrescine and betaine which are key metabolites for cell growth and viability were found to be differentially expressed by clinical isolates. These observations were supported by the transcriptional expression study of selected genes evidencing cell wall/membrane re-organisation, altered oxidative stress, and reprogramming of carbon metabolic pathways. Collectively, the study advances our understanding on adaptative response of C. glabrata in vaginal microenvironment to lactic acid for survival and virulence.


In vaginal tract, lactic acid present as a natural carbon source is a potentiating factor for vulvovaginal candidiasis caused by C. glabrata is highest. The present article delineates the lactic acid adaptation in vaginal clinical isolates of C. glabrata using a comprehensive approach of biochemical, metabolic and transcriptional studies.

20.
Mycoses ; 2022 Jun 17.
Artigo em Inglês | MEDLINE | ID: mdl-35713604

RESUMO

BACKGROUND: Candida tropicalis is a human pathogenic yeast frequently isolated in Latin America and Asian-Pacific regions, although recent studies showed that it is also becoming increasingly widespread throughout several African and south-European countries. Nevertheless, relatively little is known about its global patterns of genetic variation as most of existing multilocus sequence typing (MLST) data come from Asia and there are no genotyped African isolates. OBJECTIVES: We report detailed genotyping data from a large set of C. tropicalis isolates recovered from different clinical sources in Italy, Egypt and Cameroon in order to expand the allele/genotype library of MLST-database (https://pubmlst.org/ctropicalis), and to explore the genetic diversity in this species. METHODS: A total of 103 C. tropicalis isolates were genotyped using the MLST-scheme developed for this species. All isolates were also tested for in-vitro susceptibility to various antifungals to assess whether certain genotypes were associated with drug-resistance. RESULTS AND CONCLUSIONS: A total of 104 different alleles were detected across the MLST-loci investigated. The allelic diversity found at these loci resulted in 51 unique MLST-genotypes of which 36 (70.6%) were novel. Global optimal eBURST analysis identified 18 clonal complexes (CCs) and confirm the existence of a specific Italian-cluster (CC36). Three CCs were also statistically associated with fluconazole-resistance, which was elevated in Cameroon and Egypt. Our data show high genetic diversity in our isolates suggesting that the global population structure of C. tropicalis is still poorly understood. Moreover, its clinical impact in Italy, Egypt and Cameroon appears to be relevant and should be carefully considered.

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