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1.
J Clin Microbiol ; 62(5): e0039424, 2024 May 08.
Artigo em Inglês | MEDLINE | ID: mdl-38602412

RESUMO

Aspergillus species and Mucorales agents are the primary etiologies of invasive fungal disease (IFD). Biomarkers that predict outcomes are needed to improve care. Patients diagnosed with invasive aspergillosis and mucormycosis using plasma cell-free DNA (cfDNA) PCR were retested weekly for 4 weeks. The primary outcome included all-cause mortality at 6 weeks and 6 months based on baseline cycle threshold (CT) values and results of follow-up cfDNA PCR testing. Forty-five patients with Aspergillus and 30 with invasive Mucorales infection were retested weekly for a total of 197 tests. Using the European Organization for Research and Treatment of Cancer and the Mycoses Study Group Education and Research Consortium (EORTC/MSG) criteria, 30.7% (23/75), 25.3% (19/75), and 38.7% (29/75) had proven, probable, and possible IFD, respectively. In addition, 97.3% (73/75) were immunocompromised. Baseline CT increased significantly starting at week 1 for Mucorales and week 2 for Aspergillus. Aspergillosis and mucormycosis patients with higher baseline CT (CT >40 and >35, respectively) had a nonsignificantly higher survival rate at 6 weeks, compared with patients with lower baseline CT. Mucormycosis patients with higher baseline CT had a significantly higher survival rate at 6 months. Mucormycosis, but not aspergillosis patients, with repeat positive cfDNA PCR results had a nonsignificantly lower survival rate at 6 weeks and 6 months compared with patients who reverted to negative. Aspergillosis patients with baseline serum Aspergillus galactomannan index <0.5 and <1.0 had significantly higher survival rates at 6 weeks when compared with those with index ≥0.5 and ≥1.0, respectively. Baseline plasma cfDNA PCR CT can potentially be used to prognosticate survival in patients with invasive Aspergillus and Mucorales infections. IMPORTANCE: We show that Aspergillus and Mucorales plasma cell-free DNA PCR can be used not only to noninvasively diagnose patients with invasive fungal disease but also to correlate the baseline cycle threshold with survival outcomes, thus potentially allowing the identification of patients at risk for poor outcomes, who may benefit from more targeted therapies.


Assuntos
Ácidos Nucleicos Livres , DNA Fúngico , Infecções Fúngicas Invasivas , Mucormicose , Reação em Cadeia da Polimerase , Humanos , Mucormicose/diagnóstico , Mucormicose/mortalidade , Mucormicose/sangue , Mucormicose/microbiologia , Masculino , Feminino , Pessoa de Meia-Idade , Prognóstico , Idoso , Ácidos Nucleicos Livres/sangue , Reação em Cadeia da Polimerase/métodos , Adulto , DNA Fúngico/genética , DNA Fúngico/sangue , Infecções Fúngicas Invasivas/diagnóstico , Infecções Fúngicas Invasivas/mortalidade , Infecções Fúngicas Invasivas/microbiologia , Aspergillus/genética , Aspergillus/isolamento & purificação , Aspergilose/diagnóstico , Aspergilose/mortalidade , Aspergilose/microbiologia , Mucorales/genética , Mucorales/isolamento & purificação , Biomarcadores/sangue , Idoso de 80 Anos ou mais , Estudos Prospectivos
2.
Artigo em Inglês | MEDLINE | ID: mdl-38639759

RESUMO

During investigations of invertebrate-associated fungi in Yunnan Province of China, a new species, Sporodiniella sinensis sp. nov., was collected. Morphologically, S. sinensis is similar to Sporodiniella umbellata; however, it is distinguished from S. umbellata by its greater number of sporangiophore branches, longer sporangiophores, larger sporangiospores, and columellae. The novel species exhibits similarities of 91.62 % for internal transcribed spacer (ITS), 98.66-99.10 % for ribosomal small subunit (nrSSU), and 96.36-98.22 % for ribosomal large subunit (nrLSU) sequences, respectively, compared to S. umbellata. Furthermore, phylogenetic analyses based on combined sequences of ITS, nrLSU and nrSSU show that it forms a separate clade in Sporodiniella, and clusters closely with S. umbellata with high statistical support. The phylogenetic and morphological evidence support S. sinensis as a distinct species. Here, it is formally described and illustrated, and compared with other relatives.


Assuntos
Ácidos Graxos , Mucorales , Animais , Filogenia , China , Análise de Sequência de DNA , Composição de Bases , RNA Ribossômico 16S/genética , DNA Bacteriano/genética , Técnicas de Tipagem Bacteriana , Ácidos Graxos/química , Invertebrados
4.
Microbiol Mol Biol Rev ; 88(1): e0018822, 2024 Mar 27.
Artigo em Inglês | MEDLINE | ID: mdl-38445820

RESUMO

SUMMARYThe World Health Organization has established a fungal priority pathogens list that includes species critical or highly important to human health. Among them is the order Mucorales, a fungal group comprising at least 39 species responsible for the life-threatening infection known as mucormycosis. Despite the continuous rise in cases and the poor prognosis due to innate resistance to most antifungal drugs used in the clinic, Mucorales has received limited attention, partly because of the difficulties in performing genetic manipulations. The COVID-19 pandemic has further escalated cases, with some patients experiencing the COVID-19-associated mucormycosis, highlighting the urgent need to increase knowledge about these fungi. This review addresses significant challenges in treating the disease, including delayed and poor diagnosis, the lack of accurate global incidence estimation, and the limited treatment options. Furthermore, it focuses on the most recent discoveries regarding the mechanisms and genes involved in the development of the disease, antifungal resistance, and the host defense response. Substantial advancements have been made in identifying key fungal genes responsible for invasion and tissue damage, host receptors exploited by the fungus to invade tissues, and mechanisms of antifungal resistance. This knowledge is expected to pave the way for the development of new antifungals to combat mucormycosis. In addition, we anticipate significant progress in characterizing Mucorales biology, particularly the mechanisms involved in pathogenesis and antifungal resistance, with the possibilities offered by CRISPR-Cas9 technology for genetic manipulation of the previously intractable Mucorales species.


Assuntos
Mucorales , Mucormicose , Humanos , Mucorales/genética , Mucormicose/diagnóstico , Mucormicose/tratamento farmacológico , Mucormicose/microbiologia , Antifúngicos/uso terapêutico , Pandemias
5.
Med Mycol ; 62(4)2024 Mar 28.
Artigo em Inglês | MEDLINE | ID: mdl-38533663

RESUMO

Our objective was to determine whether the twice-weekly screening of high-risk hematology patients by Mucorales qPCR on serum affects the prognosis of mucormycosis. Results from all serum Mucorales qPCR tests performed on patients from the hematology unit from January 2017 to December 2022 were analyzed. Patients with positive results were classified as having proven, probable or 'PCR-only' mucormycosis. One-month mortality for the local cohort was compared with that of a national cohort of cases of mucormycosis collected by the French surveillance network for invasive fungal disease ('Réseau de surveillances des infections fongiques invasives en France' (RESSIF)) from 2012 to 2018. From 2017 to 2022, 7825 serum Mucorales qPCR tests were performed for patients from the hematology unit; 107 patients with at least one positive Mucorales qPCR (164 positive samples) were identified. Sixty patients (70 positive samples, median Cq = 40) had no radiological criteria for mucormycosis and were considered not to have invasive fungal disease (70/7825, 0.9% false positives). It was not possible to classify disease status for six patients (12 positive samples, median Cq = 38). Forty-one patients (82 positive samples, median Cq = 35) had a final diagnosis of mucormycosis. In comparison with the RESSIF cohort, the local cohort was independently associated with a 48% lower one-month all-cause mortality rate (age-, sex-, and primary disease-adjusted hazard ratio = 0.52; 95% confidence interval: 0.29-0.94; P 0.03). Proactive screening for invasive mold diseases in high-risk hematology patients, including twice-weekly Mucorales qPCR on serum, was associated with mucormycosis higher survival.


Assuntos
Hematologia , Infecções Fúngicas Invasivas , Mucorales , Mucormicose , Humanos , Mucorales/genética , Mucormicose/diagnóstico , Mucormicose/microbiologia , Mucormicose/veterinária , Infecções Fúngicas Invasivas/diagnóstico , Infecções Fúngicas Invasivas/veterinária , DNA Fúngico
6.
Food Chem ; 447: 139053, 2024 Jul 30.
Artigo em Inglês | MEDLINE | ID: mdl-38518616

RESUMO

The influence of four carbon and nitrogen substrates on the quality and flavor of a novel surimi-based product fermented with Actinomucor elegans (A. elegans) was investigated, with a focus on carbon and nitrogen catabolite repression. The results showed that the substrate significantly affected mycelial growth, enzyme activities, and the metabolites of A. elegans. Although glucose significantly promoted A. elegans growth by 116.69%, it decreased enzyme secretion by 69.79% for α-amylase and 59.80% for protease, most likely by triggering the carbon catabolite repression pathway. Starch, soy protein, and wheat gluten substantially affected the textural properties of the fermented surimi. Furthermore, wheat gluten significantly promoted the protease activity (102.70%) and increased protein degradation during surimi fermentation. The fishy odor of surimi was alleviated through fermentation, and a correlation between the volatile compounds and A. elegans metabolism was observed. These results explore fermentation substrates in filamentous fungi metabolism from a catabolite repression perspective.


Assuntos
Carbono , Mucorales , Endopeptidases , Fermentação , Glutens
7.
RNA ; 30(4): 354-366, 2024 Mar 18.
Artigo em Inglês | MEDLINE | ID: mdl-38307611

RESUMO

Some eukaryotic pre-tRNAs contain an intron that is removed by a dedicated set of enzymes. Intron-containing pre-tRNAs are cleaved by tRNA splicing endonuclease, followed by ligation of the two exons and release of the intron. Fungi use a "heal and seal" pathway that requires three distinct catalytic domains of the tRNA ligase enzyme, Trl1. In contrast, humans use a "direct ligation" pathway carried out by RTCB, an enzyme completely unrelated to Trl1. Because of these mechanistic differences, Trl1 has been proposed as a promising drug target for fungal infections. To validate Trl1 as a broad-spectrum drug target, we show that fungi from three different phyla contain Trl1 orthologs with all three domains. This includes the major invasive human fungal pathogens, and these proteins can each functionally replace yeast Trl1. In contrast, species from the order Mucorales, including the pathogens Rhizopus arrhizus and Mucor circinelloides, have an atypical Trl1 that contains the sealing domain but lacks both healing domains. Although these species contain fewer tRNA introns than other pathogenic fungi, they still require splicing to decode three of the 61 sense codons. These sealing-only Trl1 orthologs can functionally complement defects in the corresponding domain of yeast Trl1 and use a conserved catalytic lysine residue. We conclude that Mucorales use a sealing-only enzyme together with unidentified nonorthologous healing enzymes for their heal and seal pathway. This implies that drugs that target the sealing activity are more likely to be broader-spectrum antifungals than drugs that target the healing domains.


Assuntos
Mucorales , Proteínas de Saccharomyces cerevisiae , Humanos , RNA Ligase (ATP)/genética , RNA Ligase (ATP)/metabolismo , Saccharomyces cerevisiae/genética , RNA de Transferência/química , Proteínas de Saccharomyces cerevisiae/genética , Precursores de RNA/metabolismo , Splicing de RNA , Mucorales/genética , Mucorales/metabolismo
8.
Med Mycol ; 62(2)2024 Jan 27.
Artigo em Inglês | MEDLINE | ID: mdl-38327232

RESUMO

Mucormycosis is a rare disease with scarce diagnostic methods for early intervention. Available strategies employing direct microscopy using calcofluor white-KOH, culture, radiologic, and histopathologic testing often are time-intensive and demand intricate protocols. Nucleic Acid Amplification Test holds promise due to its high sensitivity combined with rapid detection. Loop-mediated isothermal amplification (LAMP) based detection offers an ultrasensitive technique that does not require complicated thermocyclers like in polymerase chain reaction, offering a straightforward means for improving diagnoses as a near-point-of-care test. The study introduces a novel magnetic nanoparticle-based LAMP assay for carryover contaminant capture to reduce false positives. Solving the main drawback of LAMP-based diagnosis techniques. The assay targets the cotH gene, which is invariably specific to Mucorales. The assay was tested with various species of Mucorales, and the limit of detections for Rhizopus microsporus, Lichtheimia corymbifera, Rhizopus arrhizus, Rhizopus homothallicus, and Cunninghamella bertholletiae were 1 fg, 1 fg, 0.1 pg, 0.1 pg, and 0.01 ng, respectively. This was followed by a clinical blindfolded study using whole blood and urine samples from 30 patients diagnosed with Mucormycosis. The assay has a high degree of repeatability and had an overall sensitivity of > 83%. Early Mucormycosis detection is crucial, as current lab tests from blood and urine lack sensitivity and take days for confirmation despite rapid progression and severe complications. Our developed technique enables the confirmation of Mucormycosis infection in < 45 min, focusing specifically on the RT-LAMP process. Consequently, this research offers a viable technique for quickly identifying Mucormycosis from isolated DNA of blood and urine samples instead of invasive tissue samples.


Mucormycosis is a challenging disease to diagnose early. This study introduces a sensitive and rapid diagnostic approach using Loop-mediated isothermal amplification technology. Testing blood and urine samples from 30 patients revealed promising sensitivity and repeatability, indicating its potential for non-invasive diagnosis.


Assuntos
Nanopartículas de Magnetita , Mucorales , Mucormicose , Humanos , Mucormicose/diagnóstico , Mucormicose/veterinária , Sensibilidade e Especificidade , Técnicas de Amplificação de Ácido Nucleico/métodos , Técnicas de Amplificação de Ácido Nucleico/veterinária , Técnicas de Diagnóstico Molecular/métodos , Técnicas de Diagnóstico Molecular/veterinária , Mucorales/genética
9.
Curr Pharm Des ; 30(1): 1-9, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38178658

RESUMO

BACKGROUND: Regardless of the most recent inclusion of mold-active agents (isavuconazole and posaconazole) to antifungal agents against mucormycosis, in conjunction with amphotericin B (AMB) items, numerous uncertainties still exist regarding the treatment of this rare infection. The order Mucorales contains a variety of fungi that cause the serious but uncommon fungal illness known as mucormycosis. The moulds are prevalent in nature and typically do not pose significant risks to people. Immunocompromised people are affected by it. OBJECTIVE: This article's primary goal is to highlight the integral role that AMB plays in this condition. METHODS: Like sinusitis (including pansinusitis, rhino-orbital, or rhino-cerebral sinusitis) is one of the many signs and symptoms of mucormycosis. The National Center for Biotechnology Information (NCBI) produces a variety of online information resources for review articles on the topic-based mucormycosis, AMB, diagnosis of mucormycosis and the PubMed® database of citations and abstracts published in life science journals. These resources can be accessed through the NCBI home page at https://www.ncbi.nlm.nih.gov. RESULTS: The article provides a summary of the pharmacological attributes of the various AMB compositions accessible for systemic use. CONCLUSION: The article demonstrates the traits of the drug associated with its chemical, pharmacokinetics, stability, and other features, and illustrates their most useful characteristics for clinical application.


Assuntos
Mucorales , Mucormicose , Sinusite , Humanos , Anfotericina B/uso terapêutico , Mucormicose/tratamento farmacológico , Mucormicose/diagnóstico , Mucormicose/microbiologia , Antifúngicos/uso terapêutico , Sinusite/tratamento farmacológico
10.
RNA ; 30(4): 367-380, 2024 Mar 18.
Artigo em Inglês | MEDLINE | ID: mdl-38238085

RESUMO

Fungal Trl1 is an essential trifunctional tRNA splicing enzyme that heals and seals tRNA exons with 2',3'-cyclic-PO4 and 5'-OH ends. Trl1 is composed of C-terminal cyclic phosphodiesterase and central polynucleotide kinase end-healing domains that generate the 3'-OH,2'-PO4 and 5'-PO4 termini required for sealing by an N-terminal ATP-dependent ligase domain. Trl1 enzymes are present in many human fungal pathogens and are promising targets for antifungal drug discovery because their domain structures and biochemical mechanisms are unique compared to the mammalian RtcB-type tRNA splicing enzyme. Here we report that Mucorales species (deemed high-priority human pathogens by WHO) elaborate a noncanonical tRNA splicing apparatus in which a monofunctional RNA ligase enzyme is encoded separately from any end-healing enzymes. We show that Mucor circinelloides RNA ligase (MciRNL) is active in tRNA splicing in vivo in budding yeast in lieu of the Trl1 ligase domain. Biochemical and kinetic characterization of recombinant MciRNL underscores its requirement for a 2'-PO4 terminus in the end-joining reaction, whereby the 2'-PO4 enhances the rates of RNA 5'-adenylylation (step 2) and phosphodiester synthesis (step 3) by ∼125-fold and ∼6200-fold, respectively. In the canonical fungal tRNA splicing pathway, the splice junction 2'-PO4 installed by RNA ligase is removed by a dedicated NAD+-dependent RNA 2'-phosphotransferase Tpt1. Here we identify and affirm by genetic complementation in yeast the biological activity of Tpt1 orthologs from three Mucorales species. Recombinant M. circinelloides Tpt1 has vigorous NAD+-dependent RNA 2'-phosphotransferase activity in vitro.


Assuntos
Mucorales , Animais , Humanos , Mucorales/genética , Mucorales/metabolismo , NAD/metabolismo , RNA/genética , RNA de Transferência/genética , RNA de Transferência/metabolismo , RNA Ligase (ATP)/genética , RNA Ligase (ATP)/metabolismo , Saccharomyces cerevisiae/metabolismo , Ligases , Polinucleotídeo 5'-Hidroxiquinase/química , Splicing de RNA , Mamíferos/genética
11.
Med Mycol ; 62(2)2024 Jan 27.
Artigo em Inglês | MEDLINE | ID: mdl-38289831

RESUMO

To estimate the diagnostic performance of Mucorales polymerase chain reaction (PCR) in Bronchoalveolar lavage fluid (BALF) in routine practice. This was a single-center retrospective study including all consecutive patients >18 years who underwent Mucorales PCR assay in BALF between January 2021 and May 2022. Index testing was prospectively performed using the MycoGENIE Aspergillus spp.-Mucorales spp. PCR. The reference was the diagnosis of pulmonary mucormycosis by the Adjudication Committee. Mucorales PCR in BALF was performed for 938 patients and was positive for 21 of 938 (2.2%). Eleven pulmonary mucormycosis (including one disseminated) were diagnosed. Among them, one (9.1%) was classified as proven mucormycosis, three (27.3%) as probable, and seven (63.6%) as possible according to the EORTC/MSGERC 2019 criteria. The main host factor was hematological malignancy (10 of 11, 90.9%). Mucorales PCR was positive in serum for eight patients (72.7%). Three patients had positive PCR in BALF, but negative in serum. The mean cycle threshold value was significantly lower in mucormycosis than false-positive cases. Sensitivity was 72.7% (95% confidence interval [CI], 43.4-90.3%), and specificity was 98.6% (95% CI, 97.6-99.2%). The positive and negative predictive values were 38.1% (95% CI, 20.8-59.1%) and 99.7% (95% CI, 99.1-99.9%), respectively. Mucorales PCR in BALF showed good diagnostic performance for mucormycosis, particularly in combination with serum PCR. A positive result should be interpreted with caution, given the possibility of carriage in the airway. However, its high negative predictive value and specificity suggest the utility of Mucorales PCR in BALF in the diagnosis of pulmonary mucormycosis.


Assuntos
Mucorales , Mucormicose , Humanos , Mucorales/genética , Mucormicose/diagnóstico , Mucormicose/veterinária , Líquido da Lavagem Broncoalveolar , Estudos Retrospectivos , Reação em Cadeia da Polimerase/veterinária , DNA Fúngico , Sensibilidade e Especificidade
12.
FEMS Microbiol Lett ; 3712024 01 09.
Artigo em Inglês | MEDLINE | ID: mdl-38200712

RESUMO

CrgA has been shown to be a negative regulator of carotenogenesis in some filamentous fungi, while light irradiation is an inducible environmental factor for carotenoid biosynthesis. To clarify the relationship between CrgA and light-inducible carotenogenesis in Blakeslea trispora, the cis-acting elements of the btcrgA promoter region were investigated, followed by the analyses of correlation between the expression of btcrgA and carotenoid structural genes under different irradiation conditions. A variety of cis-acting elements associated with light response was observed in the promoter region of btcrgA, and transcription of btcrgA and carotenoid structural genes under different irradiation conditions was induced by white light with a clear correlation. Then, RNA interference and overexpression of btcrgA were performed to investigate their effects on carotenogenesis at different levels under irradiation and darkness. The analyses of transcription and enzyme activities of carotenoid structural gene, and accumulation of carotenoids among btcrgA-interfered, btcrgA-overexpressed, and wild-type strains under irradiation and darkness indicate that btcrgA negatively regulates the synthesis of carotenoid in darkness, while promotes the carotenogenesis under irradiation regardless of reduced or overexpression of btcrgA .


Assuntos
Proteínas Fúngicas , Mucorales , Proteínas Fúngicas/genética , Proteínas Fúngicas/metabolismo , Mucorales/genética , Mucorales/metabolismo , Carotenoides/metabolismo , Luz
13.
Microb Pathog ; 188: 106544, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38246313

RESUMO

Fungi are opportunistic eukaryotic entities often taking advantage of susceptibilities offered by a host due to its immunocompromised status, changed microbiome, or ruptured physical barriers and eventually cause infections. They either invade the skin superficially or are deep-seated. Superficial mycosis affects the skin, hair, and nails inhabiting the outermost layer, stratum corneum. In the present study, we report a case of superficial mycosis (onychomycosis in particular) in a 45-year-old immunocompetent man who was an ex-defense personnel and presently serving as a security guard at the University of Jammu, District Jammu, Jammu and Kashmir, India. The infection evolved 17 years ago and negatively affected the quality of life of the patient. For the identification of the causal agent, direct microscopy, cultural, micro-morphological, molecular characterization (ITS sequencing), and phylogenetic analysis were taken into account. A mucoralean fungal species, Thamnostylum piriforme, was isolated from the fingernails (left hand) of the investigated patient, which represents a new global report as the causal agent of superficial mycosis. In vitro antifungal susceptibility testing showed T. piriforme sensitivity to itraconazole, amphotericin B and ketoconazole while resistance to fluconazole. Careful selection of optimal therapy for fungal infection based primarily on correct identification and antifungal susceptibility testing could provide effective results during treatment against these opportunistic human fungal pathogens.


Assuntos
Antifúngicos , Dermatomicoses , Mucorales , Masculino , Humanos , Pessoa de Meia-Idade , Antifúngicos/farmacologia , Antifúngicos/uso terapêutico , Filogenia , Qualidade de Vida , Testes de Sensibilidade Microbiana , Itraconazol/farmacologia , Itraconazol/uso terapêutico , Dermatomicoses/tratamento farmacológico
14.
mBio ; 15(1): e0284823, 2024 Jan 16.
Artigo em Inglês | MEDLINE | ID: mdl-38095437

RESUMO

IMPORTANCE: In October 2022, Mucorales fungi were listed in the "High Priority Group" on the first-ever list of fungal priority pathogens by the World Health Organization. As the causative agent of mucormycosis, Mucorales have become of great clinical and public health importance with growing mucormycosis numbers, notably with the exponential rise of COVID-19-associated mucormycosis cases. Despite the dire need, there are limited therapeutic options to treat mucormycosis. Our research fills in critical gaps of knowledge about how Mucorales fungi evade the host immune system. Specifically, we offer evidence that Mucorales block nitric oxide production, which is a key mediator and signaling molecule of the mammalian innate immune response to microbial pathogens. Our work offers new insight into immune evasion mechanisms by Mucorales fungi.


Assuntos
Mucorales , Mucormicose , Animais , Humanos , Mucormicose/microbiologia , Óxido Nítrico , Macrófagos , Imunidade Inata , Mamíferos
15.
Infect Dis (Lond) ; 56(3): 255-258, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38015560

RESUMO

Mucorales are a large order of ubiquitous saprophytic zygomycete fungi and act as opportunistic pathogens in humans. In pediatric patients, little is known about the role of Mucorales in airway colonization and infection or their role as contaminants of respiratory samples. Currently, polymerase chain reaction (PCR) is the most sensitive mode of detection Mucorales in clinical specimen. In this study, we aimed to determine the prevalence of Mucorales in bronchoalveolar lavage samples (BAL) from a large, diverse group of pediatric patients. We performed commercial Mucorales PCR (MucorGenius®, Pathonostics, Maastricht, NL, USA) on 102 thawed BAL samples of 100 patients. Mucorales PCR was negative in all samples. Our data suggest that Mucorales spp. have a low prevalence in paediatric airways and do not frequently contaminate pediatric BAL samples.


Assuntos
Mucorales , Humanos , Criança , Mucorales/genética , Prevalência , Líquido da Lavagem Broncoalveolar/microbiologia , Lavagem Broncoalveolar , Reação em Cadeia da Polimerase
16.
Infect Disord Drug Targets ; 24(1): e220823220209, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-37608614

RESUMO

Mucormycosis is a serious and invasive fungal infection caused by Mucorales fungi. This review article provides a concise overview of the pathogenesis, epidemiology, microbiology, and diagnosis of mucormycosis. The introduction section highlights the key microbiological properties of the pathogen and delves into the underlying mechanisms of mucormycosis pathogenesis, including the invasion and proliferation of the fungus within the host. The description of the disease section focuses on the epidemiology of mucormycosis, including its incidence, risk factors, and geographical distribution. It also explores the specific context of mucormycosis infection about COVID-19 and diabetes mellitus, highlighting the increased susceptibility observed in individuals with these conditions. A case study illustrates the clinical manifestations and challenges associated with mucormycosis, emphasizing the importance of early detection. Additionally, the review discusses the diagnosis of mucormycosis, emphasizing the significance of clinical assessment, radiological imaging, and microbiological tests for accurate and timely detection of the infection. Regarding treatment, the article covers the various therapeutic approaches, including antifungal therapy, surgical interventions, and management of underlying predisposing conditions. The limitations and challenges associated with treatment options are also addressed. This review aims to provide a comprehensive understanding of mucormycosis, equipping healthcare professionals with valuable insights into its pathogenesis, epidemiology, microbiology, and diagnostic strategies. By enhancing knowledge and awareness of this fungal infection, this review can improve patient outcomes through early diagnosis and appropriate management.


Assuntos
Diabetes Mellitus , Mucorales , Mucormicose , Humanos , Mucormicose/diagnóstico , Mucormicose/epidemiologia , Mucormicose/terapia , Antifúngicos/uso terapêutico , Fatores de Risco
17.
Expert Rev Mol Diagn ; 24(3): 161-167, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-37405409

RESUMO

INTRODUCTION: Mucormycosis is a highly aggressive angio-invasive disease of humans caused by Mucorales fungi. Prior to the COVID-19 pandemic, mucormycosis was a rare mycosis typically seen in immunocompromised patients with hematological malignancies or in transplant recipients. During the second wave of the pandemic, there was a dramatic increase in the disease, especially in India where a unique set of circumstances led to large numbers of life-threatening and disfiguring rhino-orbital-cerebral mucormycosis (ROCM) infections. AREAS COVERED: The review examines mucormycosis as a super-infection of COVID-19 patients, and the risk factors for COVID-19-associated mucormycosis (CAM) that drove the ROCM epidemic in India. The limitations of current diagnostic procedures are identified, and the measures needed to improve the speed and accuracy of detection discussed. EXPERT OPINION: Despite increased awareness, global healthcare systems remain unprepared for further outbreaks of ROCM. Current diagnosis of the disease is slow and inaccurate, negatively impacting on patient survival. This is most evident in low- to middle-income countries which lack suitably equipped diagnostic facilities for rapid identification of the infecting pathogens. Rapid antigen testing using point-of-care lateral-flow assays could potentially have aided in the quick and accurate diagnosis of the disease, allowing earlier intervention with surgery and Mucorales-active antifungal drugs.


Assuntos
COVID-19 , Mucorales , Mucormicose , Humanos , Mucormicose/diagnóstico , Pandemias , COVID-19/diagnóstico , Antifúngicos
18.
Sci Rep ; 13(1): 22134, 2023 12 13.
Artigo em Inglês | MEDLINE | ID: mdl-38092785

RESUMO

Mucormycosis is a severe complication in critically ill COVID-19 patients. Throughout the pandemic, a notable prevalence of mucormycosis has been observed in the Indian population, whereas lower occurrences have been reported in Europe. However, limited data exist regarding its prevalence in Europe, which is potentially underestimated due to the low sensitivity of bronchoalveolar lavage (BAL) cultures. We aimed to evaluate the prevalence of mucormycosis in a high-risk critically ill COVID-19 population in the Netherlands, and to evaluate the potential benefit of adding Mucor PCR to BAL as part of routine follow-up. In this study, we included 1035 critically ill COVID-19 patients admitted to either one of the two ICUs at AmsterdamUMC between March 2020 and May 2022; of these, 374 had undergone at least one bronchoscopy. Following the AmsterdamUMC protocols, bronchoscopies were conducted weekly until clinical improvement was achieved. We cultured BAL fluid for fungi and used PCR and galactomannan testing to detect Aspergillus spp. Additionally, we retrospectively performed qPCR targeting Mucorales DNA in the BAL of 89 deceased patients. All cultures were negative for Mucorales, whereas 42 (11%) cultures were positive for Aspergillus. Furthermore, qPCR targeting Mucorales was negative in all 89 deceased patients. This study showed that pulmonary mucormycosis was not present in critically ill COVID-19 patients in two tertiary care ICUs. These results indicate routine Mucorales qPCR screening is not clinically necessary in a high-standard-of-care tertiary ICU in a low-endemic area.


Assuntos
COVID-19 , Mucorales , Mucormicose , Humanos , Mucormicose/epidemiologia , Países Baixos/epidemiologia , Estado Terminal , Estudos Retrospectivos , COVID-19/epidemiologia , Mucorales/genética , Aspergillus/genética , Unidades de Terapia Intensiva
19.
Int J Mol Sci ; 24(24)2023 Dec 15.
Artigo em Inglês | MEDLINE | ID: mdl-38139348

RESUMO

Invasive fungal (IF) diseases are a leading global cause of mortality, particularly among immunocompromised individuals. The SARS-CoV-2 pandemic further exacerbated this scenario, intensifying comorbid IF infections such as mucormycoses of the nasopharynx. In the work reported here, it is shown that zygomycetes, significant contributors to mycoses, are sensitive to the natural product allicin. Inhibition of Mucorales fungi by allicin in solution and by allicin vapor was demonstrated. Mathematical modeling showed that the efficacy of allicin vapor is comparable to direct contact with the commercially available antifungal agent amphotericin B (ampB). Furthermore, the study revealed a synergistic interaction between allicin and the non-volatile ampB. The toxicity of allicin solution to human cell lines was evaluated and it was found that the half maximal effective concentration (EC50) of allicin was 25-72 times higher in the cell lines as compared to the fungal spores. Fungal allicin sensitivity depends on the spore concentration, as demonstrated in a drop test. This study shows the potential of allicin, a sulfur-containing defense compound from garlic, to combat zygomycete fungi. The findings underscore allicin's promise for applications in infections of the nasopharynx via inhalation, suggesting a novel therapeutic avenue against challenging fungal infections.


Assuntos
Infecções Fúngicas Invasivas , Mucorales , Micoses , Humanos , Antifúngicos/farmacologia , Antifúngicos/uso terapêutico , Mucorales/metabolismo , Anfotericina B/farmacologia , Ácidos Sulfínicos/farmacologia , Ácidos Sulfínicos/uso terapêutico , Dissulfetos/farmacologia , Micoses/tratamento farmacológico , Infecções Fúngicas Invasivas/tratamento farmacológico
20.
Front Cell Infect Microbiol ; 13: 1305662, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-38145040

RESUMO

Mucoromycosis is a highly aggressive angio-invasive disease of humans caused by fungi in the zygomycete order, Mucorales. While Rhizopus arrhizus is the principal agent of mucoromycosis, other Mucorales fungi including Apophysomyces, Cunninghamella, Lichtheimia, Mucor, Rhizomucor and Syncephalastrum are able to cause life-threatening rhino-orbital-cerebral, pulmonary, gastro-intestinal and necrotising cutaneous infections in humans. Diagnosis of the disease currently relies on non-specific CT, lengthy and insensitive culture from invasive biopsy, and time-consuming histopathology of tissue samples. At present, there are no rapid antigen tests that detect Mucorales-specific biomarkers of infection, and which allow point-of-care diagnosis of mucoromycosis. Here, we report the development of an IgG2b monoclonal antibody (mAb), TG11, which binds to extracellular polysaccharide (EPS) antigens of between 20 kDa and 250 kDa secreted during hyphal growth of Mucorales fungi. The mAb is Mucorales-specific and does not cross-react with other yeasts and molds of clinical importance including Aspergillus, Candida, Cryptococcus, Fusarium, Lomentospora and Scedosporium species. Using the mAb, we have developed a Competitive lateral-flow device that allows rapid (30 min) detection of the EPS biomarker in human serum and bronchoalveolar lavage (BAL), with a limit of detection (LOD) in human serum of ~100 ng/mL serum (~224.7 pmol/L serum). The LFD therefore provides a potential novel opportunity for detection of mucoromycosis caused by different Mucorales species.


Assuntos
Fusarium , Mucorales , Humanos , Anticorpos Monoclonais , Aspergillus , Biomarcadores
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