Emergence of zoonotic sporotrichosis in Brazil: a genomic epidemiology study.

BACKGROUND: Zoonotic sporotrichosis is a neglected fungal disease, whereby outbreaks are primarily driven by Sporothrix brasiliensis and linked to cat-to-human transmission. To understand the emergence and spread of sporotrichosis in Brazil, the epicentre of the current epidemic in South America, we aimed to conduct whole-genome sequencing (WGS) to describe the genomic epidemiology. METHODS: In this genomic epidemiology study, we included Sporothrix spp isolates from sporotrichosis cases from Brazil, Colombia, and the USA. We conducted WGS using Illumina NovaSeq on isolates collected by three laboratories in Brazil from humans and cats with sporotrichosis between 2013 and 2022. All isolates that were confirmed to be Sporothrix genus by internal transcribed spacer or beta-tubulin PCR sequencing were included in this study. We downloaded eight Sporothrix genome sequences from the National Center for Biotechnology Information (six from Brazil, two from Colombia). Three Sporothrix spp genome sequences from the USA were generated by the US Centers for Disease Control and Prevention as part of this study. We did phylogenetic analyses and correlated geographical and temporal case distribution with genotypic features of Sporothrix spp isolates. FINDINGS: 72 Sporothrix spp isolates from 55 human and 17 animal sporotrichosis cases were included: 67 (93%) were from Brazil, two (3%) from Colombia, and three (4%) from the USA. Cases spanned from 1999 to 2022. Most (61 [85%]) isolates were S brasiliensis, and all were reported from Brazil. Ten (14%) were Sporothrix schenckii and were reported from Brazil, USA, and Colombia. For S schenckii isolates, two distinct clades were observed wherein isolates clustered by geography. For S brasiliensis isolates, five clades separated by more than 100 000 single-nucleotide polymorphisms were observed. Among the five S brasiliensis clades, clades A and C contained isolates from both human and cat cases, and clade A contained isolates from six different states in Brazil. Compared with S brasiliensis isolates, larger genetic diversity was observed among S schenckii isolates from animal and human cases within a clade. INTERPRETATION: Our results suggest that the ongoing epidemic driven by S brasiliensis in Brazil represents several, independent emergence events followed by animal-to-animal and animal-to human transmission within and between Brazilian states. These results describe how S brasiliensis can emerge and spread within a country. FUNDING: Coordenação de Aperfeiçoamento de Pessoal de Nível Superior, Brazil; the São Paulo Research Foundation; Productivity in Research fellowships by the National Council for Scientific and Technological Development, and Ministry of Science and Technology of Brazil.

Antifungal Resistance in Cryptococcal Infections.

Antifungal therapy, especially with the azoles, could promote the incidence of less susceptible isolates of Cryptococcus neoformans and C. gattii species complexes (SC), mostly in developing countries. Given that these species affect mostly the immunocompromised host, the infections are severe and difficult to treat. This review encompasses the following topics: 1. infecting species and their virulence, 2. treatment, 3. antifungal susceptibility methods and available categorical endpoints, 4. genetic mechanisms of resistance, 5. clinical resistance, 6. fluconazole minimal inhibitory concentrations (MICs), clinical outcome, 7. environmental influences, and 8. the relevance of host factors, including pharmacokinetic/pharmacodynamic (PK/PD) parameters, in predicting the clinical outcome to therapy. As of now, epidemiologic cutoff endpoints (ECVs/ECOFFs) are the most reliable antifungal resistance detectors for these species, as only one clinical breakpoint (amphotericin B and C. neoformans VNI) is available.

Bimodal distribution of azole susceptibility in Sporothrix brasiliensis isolates in Brazil.

Sporothrix brasiliensis is an emerging zoonotic fungal pathogen that can be difficult to treat. Antifungal susceptibility testing was performed on the mold phase of a convenience sample of 61 Sporothrix spp. isolates from human and cat sporotrichosis cases in Brazil using the Clinical and Laboratory Standards Institute standard M38. A bimodal distribution of azole susceptibility was observed with 50% (28/56) of S. brasiliensis isolates showing elevated itraconazole minimum inhibitory concentrations ≥16 µg/mL. Phylogenetic analysis found the in vitro resistant isolates were not clonal and were distributed across three different S. brasiliensis clades. Single nucleotide polymorphism (SNP) analysis was performed to identify potential mechanisms of in vitro resistance. Two of the 28 resistant isolates (MIC ≥16 mg/L) had a polymorphism in the cytochrome P450 gene, cyp51, corresponding to the well-known G448S substitution inducing azole resistance in Aspergillus fumigatus. SNPs corresponding to other known mechanisms of azole resistance were not identified in the remaining 26 in vitro resistant isolates.

Non-pharmacological therapies for pain management in paediatric intensive care units: a protocol for a scoping review.

INTRODUCTION: In critically ill children, pain management is complex owing to cognitive development and the nature of hospitalisation in paediatric intensive therapy units. Although there are many protocols and guidelines for pain control via pharmacological interventions, non-pharmacological practices should also be explored and disseminated for their potential benefit. METHODS AND ANALYSIS: A systematic literature search will be performed using the following databases: Academic Search Premier, Cumulative Index to Nursing and Allied Health Literature, Cochrane Library, Excerpta Medica Database, Virtual Health Library, Medical Literature Analysis and Retrieval System Online, ScienceDirect, Scopus, Web of Science Core Collection, Theses from Coordenação de Aperfeiçoamento de Pessoal de Nível Superior, Dart Europe, Open Access Theses and Dissertations and grey literature from Google Scholar. The research will consider quantitative and qualitative studies, mixed-method studies, systematic reviews, text articles, opinion articles, letters to editors and editorials in any language and from any database. The following will be eligible for inclusion: (1) newborns, infants, children and adolescents; and (2) non-pharmacological therapies used for pain in paediatric intensive care. ETHICS AND DISSEMINATION: This study does not require ethical approval. The results of this research will be disseminated through social media channels and podcasts about pain in children. TRIAL REGISTRATION NUMBER: This protocol has been registered with the Open Science Framework (DOI 10.17605/OSF.IO/DZHKT).

Rapid response of a public health reference laboratory to the COVID-19 pandemic.

Introduction. Brazil was one of the most affected countries by the COVID-19 pandemic. Instituto Adolfo Lutz (IAL) is the reference laboratory for COVID-19 in São Paulo, the most populous state in Brazil. In April 2020, a secondary diagnostic pole named IAL-2 was created to enhance IAL's capacity for COVID-19 diagnosis.Hypothesis/Gap Statement. Public health laboratories must be prepared to rapidly respond to emerging epidemics or pandemics.Aim. To describe the design of IAL-2 and correlate the results of RT-qPCR tests for COVID-19 with secondary data on suspected cases of SARS-CoV-2 infection in the São Paulo state.Methodology. This is a retrospective study based on the analysis of secondary data from patients suspected of infection by SARS-CoV-2 whose clinical samples were submitted to real-time PCR after reverse transcription (RT-qPCR) at IAL-2, between 1 April 2020 and 8 March 2022. RT-qPCR Ct results of the different kits used were also analysed.Results. IAL-2 was implemented in April 2020, just over a month after the detection of the first COVID-19 case in Brazil. The laboratory performed 304,250 RT-qPCR tests during the study period, of which 98 319 (32.3 %) were positive, 205827 (67.7 %) negative, and 104 (0.03 %) inconclusive for SARS-CoV-2. RT-qPCR Ct values≤30 for E/N genes of SARS-CoV-2 were presented by 79.7 % of all the samples included in the study.Conclusion. IAL was able to rapidly implement a new laboratory structure to support the processing of an enormous number of samples for diagnosis of COVID-19, outlining strategies to carry out work with quality, using different RT-qPCR protocols.

Detection of herpesviruses in neotropical primates from São Paulo, Brazil.

Transmission of herpesvirus between humans and non-human primates represents a serious potential threat to human health and endangered species conservation. This study aimed to identify herpesvirus genomes in samples of neotropical primates (NTPs) in the state of São Paulo, Brazil. A total of 242 NTPs, including Callithrix sp., Alouatta sp., Sapajus sp., and Callicebus sp., were evaluated by pan-herpesvirus polymerase chain reaction (PCR) and sequencing. Sixty-two (25.6%) samples containing genome segments representative of members of the family Herpesviridae, including 16.1% for Callitrichine gammaherpesvirus 3, 6.1% for Human alphaherpesvirus 1, 2.1% for Alouatta macconnelli cytomegalovirus, and 0.83% for Cebus albifrons lymphocryptovirus 1. No co-infections were detected. The detection of herpesvirus genomes was significantly higher among adult animals (p = 0.033) and those kept under human care (p = 0.008671). These findings confirm the importance of monitoring the occurrence of herpesviruses in NTP populations in epizootic events.

Organizational factors and safe food handling by food service workers: a scoping review protocol.

OBJECTIVE: The objective of this scoping review is to explore and map the scientific evidence on organizational factors related to safe food handling by food service workers to prevent foodborne disease. INTRODUCTION: According to the World Health Organization, more than 600 million people become ill each year due to foodborne diseases. Improper food handling is one of the main causes of such diseases. Despite the growing literature on safe food handling, many studies focus on assessing and discussing cognitive variables, such as food safety knowledge. This indicates a need to study this topic from a new perspective, for example, through its organizational factors. INCLUSION CRITERIA: The review will include quantitative and qualitative studies on food handlers (ie, individuals who have direct or indirect contact with food during their professional duties) working in food services (ie, institutional or commercial establishments). Food handlers involved in industrial processing, planting, harvesting, or working on the street (street food) or in the home will be excluded. Eligible studies will explore the organizational factors of safe food handling that influence employee behavior regarding food production. METHODS: This review will use the JBI methodology for scoping reviews to identify published and unpublished studies in all languages, with no date limit. The following databases will be searched: Scopus, CINAHL, Embase, Web of Science, MEDLINE, PsycINFO, and Food Science and Technology Abstracts. A structured search for gray literature will also be conducted. Titles, abstracts, and full texts of articles will be screened by 2 independent reviewers for inclusion, with discrepancies resolved by a third reviewer. Data will be extracted using a standardized form. The results will be summarized in tabular or graphical format, accompanied by a narrative summary. KEY DETAILS OF THIS REVIEW PROJECT ARE AVAILABLE IN OPEN SCIENCE FRAMEWORK: https://osf.io/hxfe4.

Species and antifungal susceptibility profile of agents causing vulvovaginal candidiasis in a military population: a cross-sectional study.

Military women on active duty are exposed to constant physical and mental demands, which may predispose them to some infection risks, including vulvovaginal candidiasis (VVC), a pathology considered a global public health problem. To monitor the prevalent and emerging pathogens in VVC, this study aimed to evaluate the distribution of yeast species and their in vitro antifungal susceptibility profile. We studied 104 vaginal yeast specimens obtained during routine clinical examinations. The population was attended at the Medical Center of the Military Police, São Paulo, Brazil, and was divided into two groups: infected patients (VVC) and colonised patients. Species were identified by phenotypic and proteomic methods (MALDI-TOF MS) and susceptibility to eight antifungal drugs, including azoles, polyenes, and echinocandins, was determined using microdilution broth. Candida albicans stricto sensu was found to be the most frequently isolated species (55%), but we observed a considerable rate of other Candida species isolates (30%), including Candida orthopsilosis stricto sensu only in the infected group. There were also other rare genera such as Rhodotorula, Yarrowia, and Trichosporon (15%), of which Rhodotorula mucilaginosa was the most prevalent in both groups. Fluconazole and voriconazole had the highest activity against all species in both groups. Candida parapsilosis was the most susceptible species, except for amphotericin-B in the infected group. Of note, we observed unusual resistance in C. albicans. Our results have allowed us to compile an epidemiological database on the etiology of VVC to support the empirical treatment and improve the health care of military women.

Vulvovaginal candidiasis (VVC) is an infection caused by fungi, mainly Candida albicans. Our results show that fungi other than C. albicans can cause VVC. So, our findings may help to choose the most appropriate treatment, as some may be resistant, to improve the quality of life of military women.

Disseminated Mucor indicus infection in a marmoset (Callithrix sp.).

Mucormycosis is rarely described in Platyrrhines. Herein, we describe the pathologic and molecular features of a gastric and hepatic infection by Mucor indicus in a marmoset (Callithrix sp.).

Infections by entomopathogenic fungi in common green iguanas (Iguana iguana) in captivity in Brazil.

Entomopathogenic fungi, widely available biological agents used to control agricultural pests, are sporadically reported to cause focal or disseminated infection in reptiles and mammals, including humans. This study summarizes the clinical presentation, histopathological and molecular findings by panfungal polymerase chain reaction and sequencing of four cases of hypocrealean fungal infections in captive common green iguanas (Iguana, iguana). One case of granulomatous pneumonia, hepatitis and serositis was related to Metarhizium flavoviride complex infection. Two disseminated fungal infection cases, with scarce inflammatory cell infiltration, were caused by Beauveria bassiana while there was one case of multifocal granulomatous and necrotizing pneumonia by Purpureocillium spp. To the best of our knowledge, this is the first report of fatal mycosis infection due to entomopathogenic fungi in captive common green iguanas.

Comparing the phenotypic, genotypic, and proteomic identification of Trichosporon species: A globally emerging yeast of medical importance.

Trichosporon spp. are widely distributed in the nature, comprising species that inhabit different ecological niches and can be found in the water, soil, and body surface of animals and humans. Such microorganisms have been classically associated with superficial infections; however, in the last decades, they have also been related to disseminated infections in immunocompromised patients, behaving as opportunistic agents, which demands rapid and accurate species identification for efficient therapy. Concordance level between the traditional phenotypic method and the molecular technique (gold standard) in the identification of all 59 Trichosporon samples was 59.3%. Identification concordance between MALDI-TOF spectrometry and the molecular technique was 71.2%. No isolate of environmental origin was identifiable by MALDI-TOF mass spectrometry (MS), and 100% of such environmental isolates were discordant for IGS region sequencing and phenotypic characterization. Both comparisons evidenced greatest concordance in the identification of T. asahii. The species T. debeurmannianum, T. dermatis, T. venhuisii and T. insectorum were not properly identified by both MALDI-TOF MS and the phenotypic technique. MALDI-TOF MS, in particular, seems to be appropriate to investigate yeasts of the genus Trichosporon; however, database updates are still necessary, especially for species that are not common in the clinical routine. With the aim of helping understand the aspects involved in early and accurate diagnosis of infections caused by this opportunistic agent, the present study compared the phenotypic, molecular (IGS region) and mass-spectrometry (MALDI-TOF) identification of 59 yeasts of the genus Trichosporon which had clinical and environmental origin and were kept in a mycology collection.

The present study compared the phenotypic, genotypic, and mass-spectrometry (MALDI-TOF) identification of 59 yeasts of the genus Trichosporon. MALDI-TOF MS, in particular, seems to be appropriate to investigate this yeasts when compared to a molecular technique (gold standard).

Effect of post-storage filters vs. pre-storage filters for leukoreduction of blood components on clinical outcomes: a systematic review protocol.

OBJECTIVE: This review will synthesize the best available evidence on the effectiveness of leukocyte reduction by comparing post-storage and pre-storage filters. The review will consider the following clinical outcomes: transfusion reactions, bacterial infection, length of stay, and mortality. INTRODUCTION: Transfusion is a relevant therapy, but it is not risk-free. Leukocyte reduction can be performed either by apheresis or by pre- or post-storage filters in order to reduce the risk of transfusion reactions, transmission of some diseases, alloimmunization, and platelet refractoriness. It can also reduce the length of hospital stay and the use of antibiotics. INCLUSION CRITERIA: Studies comparing the transfusion of leukocyte reduction through post-storage filters with pre-storage filters in patients of any age who received a transfusion and the clinical outcomes resulting from the transfusion will be considered for inclusion. Studies in Portuguese, English, and Spanish will be considered, with no publication time limit. METHODS: The research sources will include MEDLINE (PubMed), CINAHL (EBSCO), PsycINFO, Scopus, The Cochrane Library, Web of Science Core Collection, Embase, LILACS, and gray literature sources. The selection of titles and abstracts will be carried out by two independent reviewers, and the critical evaluation of the studies will be based on JBI tools. The data of interest for the review question will be extracted using JBI SUMARI. A narrative synthesis will be performed as will a meta-analysis and risk assessment of publication bias, if possible. SYSTEMATIC REVIEW REGISTRATION: PROSPERO: CRD42020192202.

Concurrent yellow fever and pulmonary aspergillosis due to Aspergillus fumigatus in a free-ranging howler monkey (Alouatta sp).

Herein, we describe a unique case of concomitant angioinvasive pulmonary aspergillosis due to Aspergillus fumigatus and yellow fever in a free-ranging howler monkey (Alouatta sp). Lung samples were negative for influenza viruses A and B.

One-step Multiplex Real-time RT-PCR for Molecular Detection and Typing of Dengue Virus Infection From Paraffin-embedded Tissues During the Brazilian 2019 Outbreak.

Formalin-fixed paraffin-embedded (FFPE) tissues are an important source for investigation of dengue virus (DENV) infection, particularly when blood or fresh frozen (FF) samples are unavailable. Histopathologic features and immunohistochemistry may have poor sensitivity and serotype determination is not always possible. Viral RNA genome detection tests are faster and considered the most sensitive technique for this kind of analysis, however, the use of molecular methods applied to FFPE tissues is still limited. The authors applied a single-step multiplex reverse transcription-quantitative polymerase chain reaction (RT-qPCR) for the investigation of DENV infection and typing to FFPE samples of 32 fatal cases received during the 2019 outbreak that occurred in São Paulo state, Brazil. The authors compared the results with those obtained using FF tissues. Of the 24 cases with both FF and FFPE samples, 22 (91.67%) of the FF and 19 (76.20%) of the FFPE specimens were positive. Two cases (8.33%) tested negative in both types of samples. All 8 cases with only FFPE samples available were positive. The accuracy (87.5%) of the RT-qPCR for DENV in FFPE samples were satisfactory. Although the cycle quantification (Cq) values were significantly higher in these materials (P<0.0001, Wilcoxon signed-rank test) when compared with FF tissues, Spearman's rank coefficient indicated a good correlation between the Cq values from both sample types (P=0.0063; rho=0.576). RT-qPCR applied to FFPE samples improved detection of DENV in fatal cases and represents a useful tool for diagnosis and epidemiologic studies.

Culture Cell Block Controls as a Tool to the Biomolecular Diagnosis of Infectious Diseases.

The cell block (CB) technique has allowed easy obtainment of samples such as cellular and culture suspensions, to perform specific molecular tests such as immunohistochemistry and in situ hybridization. It has been improved along time, accuracy, and quality of the diagnoses, however, the cost of a commercial gel matrix for the preparation of CB is high and not suitable depending on the situation. The objective of this study is to test agarose as an alternative to the commercial gel matrix in the preparation of Aspergillus fumigatus' CB.

Antifungal Susceptibility of Candida Species Isolated from Horticulturists with Onychomycosis in Piauí, Brazil.

BACKGROUND: We aimed to assess susceptibility pattern of Candida species isolated from horticulturists with onychomycosis to four antifungal drugs and to compare the effectiveness of conventional identification methods with matrix-assisted laser desorption/ionization mass spectrometry (MALDI-TOF MS). METHODS: This study was conducted in a community garden located in Teresina, State of Piauí, Brazil, in the year 2014. The samples were identified through phenotypic methods and per MALDI-TOF MS, being used PCR as definitive identification test. The susceptibility pattern to four antifungal drugs was determined according to Clinical and Laboratory Standards Institute (CLSI). RESULTS: Fourteen clinical isolates from seven different species were identified by the phenotypic method and by MALDI-TOF MS, with an observed concordance of 71.4% between the two methods. C. albicans (28.6%), C. parapsilosis (21.4%), C. guilliermondii and C. metapsilosis (both with 14.3%) were the most frequent species. With the exception of C. krusei, all species were sensitive to the tested antifungal. CONCLUSION: This is the first study of antifungal susceptibility of Candida in Piauí, Brazil. With the exception of C. krusei, no species showed resistance to the antifungal drugs used. This study suggests constants updates from the public databases used in MALDI-TOF MS to provide a rapid and accurate mycological diagnosis.

Effectiveness of rifampicin chemoprophylaxis in preventing leprosy in patient contacts: a systematic review of quantitative and qualitative evidence.

BACKGROUND: Individuals in contact with patients who have leprosy have an increased risk of disease exposure, which reinforces the need for chemoprophylactic measures, such as the use of rifampicin. OBJECTIVES: The objective of the review was to synthesize the best available evidence regarding the effectiveness of rifampicin chemoprophylaxis for contacts with patients with leprosy, and to synthesize the best available evidence on the experience and acceptability of rifampicin chemoprophylaxis as reported by the contacts and health professionals involved in the treatment of leprosy or Hansen's disease. INCLUSION CRITERIA TYPES OF PARTICIPANTS: In the quantitative component, individuals in contact with leprosy patients were included. In the qualitative component, in addition to contacts, health professionals who were in the practice of treating leprosy were included. TYPES OF INTERVENTION(S)/PHENOMENA OF INTEREST: The quantitative component considered as an intervention rifampicin at any dose, frequency and mode of administration, and rifampicin combination regimens.The qualitative component considered as phenomena of interest the experience and acceptability of rifampicin chemoprophylaxis. TYPES OF STUDIES: The quantitative component considered experimental and observational studies whereas the qualitative component considered studies that focused on qualitative data, including but not limited to, designs such as phenomenology, grounded theory, ethnography and action-research. OUTCOMES: The quantitative component considered studies that reported on outcomes such as the development of clinical leprosy in the contacts of patients who had leprosy, incidence rates, adverse effects and safety/harmful effects of the intervention. SEARCH STRATEGY: A three-step strategy for published and unpublished literature was used. The search for published studies included: PubMed, Cumulative Index to Nursing and Allied Health Literature, Cochrane Library, Scopus, Web of Science, National Institute for Health and Clinical Excellence, Latin American and Caribbean Health Sciences Literature; and Google Scholar and EVIPnet for unpublished studies. Studies published from the time of the respective database inception to January 2016 in English, Spanish, Portuguese, Japanese and Chinese were considered. METHODOLOGICAL QUALITY: Two reviewers independently assessed the studies for methodological quality using standardized critical appraisal instruments from the Joanna Briggs Institute. DATA EXTRACTION: Standardized data extraction tools developed by the Joanna Briggs Institute were used to extract quantitative and qualitative data from papers included in the review. DATA SYNTHESIS: Due to clinical and methodological heterogeneity in the interventions of the included studies, no statistical meta-analysis was possible. Quantitative and qualitative research findings are presented in narrative form. RESULTS: Following critical appraisal, eight studies were included in this review, seven quantitative and one qualitative. The reduction in incidence of leprosy, using one dose of rifampicin in the first two years, was 56.5%; in the follow up period of one to four years, the reduction was 34.9%. The combination of rifampicin and the Bacillus Calmette-Guérin vaccine showed a preventative effect of 80% against the disease. The only controlled clinical trial using two doses of rifampicin was community-based and did not indicate effectiveness of the intervention. The qualitative findings showed social acceptability of rifampicin. CONCLUSIONS: Chemoprophylaxis with one dose of rifampicin is found to be effective in preventing contacts of leprosy patients from contracting the disease. Also, there is indication that this strategy is socially accepted.

Amino Acid Permeases and Virulence in Cryptococcus neoformans.

Fungal opportunistic pathogens colonize various environments, from plants and wood to human and animal tissue. Regarding human pathogens, one great challenge during contrasting niche occupation is the adaptation to different conditions, such as temperature, osmolarity, salinity, pressure, oxidative stress and nutritional availability, which may constitute sources of stress that need to be tolerated and overcome. As an opportunistic pathogen, C. neoformans faces exactly these situations during the transition from the environment to the human host, encountering nutritional constraints. Our previous and current research on amino acid biosynthetic pathways indicates that amino acid permeases are regulated by the presence of the amino acids, nitrogen and temperature. Saccharomyces cerevisiae and Candida albicans have twenty-four and twenty-seven genes encoding amino acid permeases, respectively; conversely, they are scarce in number in Basidiomycetes (C. neoformans, Coprinopsis cinerea and Ustilago maydis), where nine to ten permease genes can be found depending on the species. In this study, we have demonstrated that two amino acid permeases are essential for virulence in C. neoformans. Our data showed that C. neoformans uses two global and redundant amino acid permeases, Aap4 and Aap5 to respond correctly to thermal and oxidative stress. Double deletion of these permeases causes growth arrest in C. neoformans at 37°C and in the presence of hydrogen peroxide. The inability to uptake amino acid at a higher temperature and under oxidative stress also led to virulence attenuation in vivo. Our data showed that thermosensitivity caused by the lack of permeases Aap4 and Aap5 can be remedied by alkaline conditions (higher pH) and salinity. Permeases Aap4 and Aap5 are also required during fluconazole stress and they are the target of the plant secondary metabolite eugenol, a potent antifungal inhibitor that targets amino acid permeases. In summary, our work unravels (i) interesting physiological property of C. neoformans regarding its amino acid uptake system; (ii) an important aspect of virulence, which is the need for amino acid permeases during thermal and oxidative stress resistance and, hence, host invasion and colonization; and (iii) provides a convenient prototype for antifungal development, which are the amino acid permeases Aap4/Aap5 and their inhibitor.

Caracterização molecular e perfil de suscetibilidade de Cryptococcus e outras leveduras melanizadas de ambiente contaminado com fungicidas azólicos

Cepas fúngicas ambientais estão sujeitas, continuamente, à grande diversidade de ações antrópicas, como a exposição a f u n g i c i d a, o que poderia induzir à resistência adquirida a fármacos antifúngicos com estrutura química e mecanismo de ação semelhante. A resistência adquirida a fármacos azólicos(fluconazol, itraconazol, v o r i c o n a z o l, etc.) tem importante implicação clínica.O objetivo deste estudo foi isolar e caracterizar leveduras melanizadas de origem ambiental, do gênero Cryptococcus e do grupo Black Yeast Fungi (BYF),e determinar seu perfil de sensibilidade a fármacos e fungicidas azólicos...

Environmental fungal strains are subject continuously to the wide range of humanactivities, such as exposure to fungicide, which could lead to acquired resistance to antifungal drugs with similar chemical structure and mechanism of action. Theacquired resistance to azole drugs (fluconazole, itraconazole, voriconazole, etc.)has important clinical implications. The aim of this study was to isolate and characterize melanized yeast environmental origin, gender Cryptococcus and Black Yeast Fungi group (BYF), and determine its susceptibility profile to drugs and azole fungicides...