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1.
Med Mycol ; 62(7)2024 Jul 04.
Artigo em Inglês | MEDLINE | ID: mdl-38806253

RESUMO

Candida lusitaniae fungemia is a serious infection that is rarely reported in children. The aim of this study is to describe a case series of C. lusitaniae fungemia and review previous publications regarding this rare pathogen. This is a multicenter case series of children diagnosed with C. lusitaniae fungemia. A total of 18 cases that occurred over a 15-year period in five tertiary hospitals were included. Additionally, a review of the literature regarding C. lusitaniae fungemia in children was performed. A total of 18 cases were enrolled; 11/18 (61%) were males, with a mean age of 2.3 years. All patients had severe underlying diseases and risk factors for opportunistic infection, most commonly prematurity and malignancies. More than one-third of cases occurred during the last 2 years of the study period. All isolates were susceptible to all tested antifungals. The survival rate following the acute infection was 94%, whereas the survival rate of 14 previously published cases was 71%, with the most common underlying diseases being CGD and malignancies. Candida lusitaniae fungemia is not a common event in the pediatric population, occurring exclusively in children with severe underlying diseases and significant risk factors. This cohort revealed better clinical outcomes than previously reported. All tested isolates were susceptible to all antifungal agents; variability in susceptibility as previously reported was not found in this study. The allegedly higher rate of infection in recent years is in need of further investigation in larger prospective studies in order to conclude if a real trend is at play.


Candida lusitaniae fungemia is a serious infection rarely reported in children. This cohort revealed better clinical outcomes than previously reported. All tested isolates were susceptible to all antifungal agents. The higher rate of infection in recent years is in need of further investigation.


Assuntos
Antifúngicos , Candida , Pré-Escolar , Feminino , Humanos , Masculino , Antifúngicos/uso terapêutico , Antifúngicos/farmacologia , Candida/efeitos dos fármacos , Candida/genética , Candida/isolamento & purificação , Candida/patogenicidade , Candidemia/microbiologia , Candidemia/epidemiologia , Fungemia/microbiologia , Fungemia/mortalidade , Testes de Sensibilidade Microbiana , Estudos Retrospectivos , Fatores de Risco , Centros de Atenção Terciária/estatística & dados numéricos
3.
PLoS One ; 19(5): e0302629, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38781160

RESUMO

BACKGROUND: We investigated the spectrum of infection and risk factors for invasive fungal disease due to Candida auris (CA) in Qatar. METHODS: We performed structured chart reviews on individuals with any positive CA culture between May 2019 and December 2022 at three tertiary care hospitals in Qatar. Invasive CA disease (ICAD) was defined as a positive sterile site culture, or any positive culture for CA with appropriate antifungal prescription. Main outcomes included proportion of individuals who developed ICAD among those with positive cultures, and 30-day/in-hospital mortality. RESULTS: Among 331 eligible individuals, median age was 56 years, 83.1% were male, 70.7% were non-Qataris, and 37.5% had ≥ 3 comorbidities at baseline. Overall, 86.4% were deemed to have colonization and 13.6% developed ICAD. Those with ICAD were more likely to have invasive central venous or urinary catheterization and mechanical ventilation. Individuals with ICAD had longer prior ICU stay (16 vs 26 days, P = 0.002), and longer hospital length of stay (63 vs. 43 days; P = 0.003), and higher 30-day mortality (38% vs. 14%; P<0.001). In multivariable regression analysis, only mechanical ventilation was associated with a higher risk of ICAD (OR 3.33, 95% CI 1.09-10.17). CONCLUSION: Invasive Candida auris Disease is associated with longer hospital stay and higher mortality. Severely ill persons on mechanical ventilation should be especially monitored for development of ICAD.


Assuntos
Mortalidade Hospitalar , Humanos , Masculino , Catar/epidemiologia , Feminino , Pessoa de Meia-Idade , Fatores de Risco , Idoso , Candidíase/epidemiologia , Candidíase/microbiologia , Candidíase/mortalidade , Candidíase/tratamento farmacológico , Adulto , Candida auris , Candidíase Invasiva/epidemiologia , Candidíase Invasiva/mortalidade , Candidíase Invasiva/microbiologia , Candidíase Invasiva/tratamento farmacológico , Antifúngicos/uso terapêutico , Tempo de Internação , Estudos Retrospectivos , Candida/isolamento & purificação , Candida/patogenicidade
4.
World J Gastroenterol ; 30(16): 2281-2284, 2024 Apr 28.
Artigo em Inglês | MEDLINE | ID: mdl-38690016

RESUMO

The following are our views regarding the "letter to the editor" (Helicobacter is preserved in yeast vacuoles! Does Koch's postulates confirm it?) by Alipour and Gaeini, and the response "letter to the editor" (Candida accommodates non-culturable Helicobacter pylori in its vacuole-Koch's postulates aren't applicable) by Siavoshi and Saniee. Alipour and Gaeini rejected the methods, results, discussion, and conclusions summarized in a review article by Siavoshi and Saniee. The present article reviews and discusses evidence on the evolutionary adaptation of Helicobacter pylori (H. pylori) to thrive in Candida cell vacuoles and concludes that Candida could act as a Trojan horse, transporting potentially infectious H. pylori into the stomach of humans.


Assuntos
Infecções por Helicobacter , Helicobacter pylori , Helicobacter pylori/patogenicidade , Humanos , Infecções por Helicobacter/microbiologia , Candida/fisiologia , Candida/crescimento & desenvolvimento , Candida/patogenicidade , Vacúolos/microbiologia , Vacúolos/metabolismo , Estômago/microbiologia , Mucosa Gástrica/microbiologia
5.
Sci Rep ; 14(1): 11597, 2024 05 21.
Artigo em Inglês | MEDLINE | ID: mdl-38773138

RESUMO

Candida is the most prevalent fungal bloodstream infection (BSI) with a high mortality rate among hospitalized patients. Another concern facing physicians is rising global incidence of drug-resistant Candida. This study aimed to characterize the prevalence, antifungal susceptibility, biofilm formation, and virulence genes (HWP1, ALS1, SAP2) of different Candida spp. isolated from patients with candidemia. 52 isolates of Candida spp. were identified from blood cultures by chromogenic Candida agar and confirmed by the VITEK 2 system. Isolates were tested for antifungal susceptibility by disk diffusion and VITEK 2 system. Biofilm formation and investigated genes were detected by the Congo red method and conventional PCR, respectively. Candida spp. caused 2.3% of detected BSIs, of which 32.7% were caused by Candida albicans (C. albicans) and 67.3% by non-albicans Candida (NAC), with the predominance of C. tropicalis (25%), followed by C. parapsilosis (17.3%), and C. krusei (13.5%). The susceptibility rates to fluconazole, voriconazole, caspofungin, micafungin, amphotericin B, and flucytosine were 64.7%, 76.5%, 100.0%, 100%, 100.0%, and 100.0% in C. albicans, while 53.6%, 71.4%, 91.4%, 91.4%, 94.3%, and 94.3% in NAC, respectively. Biofilm production, HWP1, ALS1, and SAP2 were detected in 70.6%, 82.4%, 76.5%, and 52.9% of C. albicans and 74.3%, 85.7%, 80.0%, and 48.6% of NAC, respectively. There is remarkable shift to NAC BSIs and high azole resistance. Antifungal stewardship and analysis of risk factors associated with this shift are needed.


Assuntos
Antifúngicos , Biofilmes , Candida , Candidemia , Farmacorresistência Fúngica , Testes de Sensibilidade Microbiana , Humanos , Candidemia/microbiologia , Candidemia/tratamento farmacológico , Candidemia/epidemiologia , Antifúngicos/farmacologia , Biofilmes/efeitos dos fármacos , Biofilmes/crescimento & desenvolvimento , Candida/efeitos dos fármacos , Candida/isolamento & purificação , Candida/patogenicidade , Candida/genética , Fatores de Virulência/genética , Virulência , Feminino , Masculino , Pessoa de Meia-Idade , Adulto
6.
Life Sci Alliance ; 7(7)2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38719750

RESUMO

Celiac disease (CD) is an autoimmune enteropathy resulting from an interaction between diet, genome, and immunity. Although many patients respond to a gluten-free diet, in a substantive number of individuals, the intestinal injury persists. Thus, other factors might amplify the ongoing inflammation. Candida albicans is a commensal fungus that is well adapted to the intestinal life. However, specific conditions increase Candida pathogenicity. The hypothesis that Candida may be a trigger in CD has been proposed after the observation of similarity between a fungal wall component and two CD-related gliadin T-cell epitopes. However, despite being implicated in intestinal disorders, Candida may also protect against immune pathologies highlighting a more intriguing role in the gut. Herein, we postulated that a state of chronic inflammation associated with microbial dysbiosis and leaky gut are favorable conditions that promote C. albicans pathogenicity eventually contributing to CD pathology via a mast cells (MC)-IL-9 axis. However, the restoration of immune and microbial homeostasis promotes a beneficial C. albicans-MC cross-talk favoring the attenuation of CD pathology to alleviate CD pathology and symptoms.


Assuntos
Candida albicans , Doença Celíaca , Homeostase , Mastócitos , Doença Celíaca/imunologia , Doença Celíaca/microbiologia , Doença Celíaca/metabolismo , Humanos , Candida albicans/patogenicidade , Candida albicans/imunologia , Mastócitos/imunologia , Mastócitos/metabolismo , Microbioma Gastrointestinal/imunologia , Disbiose/imunologia , Candidíase/imunologia , Candidíase/microbiologia , Animais , Candida/patogenicidade , Candida/imunologia , Mucosa Intestinal/microbiologia , Mucosa Intestinal/imunologia , Mucosa Intestinal/metabolismo
7.
Int J Mol Sci ; 25(9)2024 Apr 27.
Artigo em Inglês | MEDLINE | ID: mdl-38731993

RESUMO

Extracellular proteases are key factors contributing to the virulence of pathogenic fungi from the genus Candida. Their proteolytic activities are crucial for extracting nutrients from the external environment, degrading host defenses, and destabilizing the internal balance of the human organism. Currently, the enzymes most frequently described in this context are secreted aspartic proteases (Saps). This review comprehensively explores the multifaceted roles of Saps, highlighting their importance in biofilm formation, tissue invasion through the degradation of extracellular matrix proteins and components of the coagulation cascade, modulation of host immune responses via impairment of neutrophil and monocyte/macrophage functions, and their contribution to antifungal resistance. Additionally, the diagnostic challenges associated with Candida infections and the potential of Saps as biomarkers were discussed. Furthermore, we examined the prospects of developing vaccines based on Saps and the use of protease inhibitors as adjunctive therapies for candidiasis. Given the complex biology of Saps and their central role in Candida pathogenicity, a multidisciplinary approach may pave the way for innovative diagnostic strategies and open new opportunities for innovative clinical interventions against candidiasis.


Assuntos
Ácido Aspártico Proteases , Candidíase , Interações Hospedeiro-Patógeno , Humanos , Ácido Aspártico Proteases/metabolismo , Candidíase/microbiologia , Candida/patogenicidade , Candida/enzimologia , Biofilmes/crescimento & desenvolvimento , Animais , Proteínas Fúngicas/metabolismo
8.
J Mycol Med ; 34(2): 101482, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38763122

RESUMO

Fungal infections in neonatal intensive care units (NICU) are mainly related to Candida species, with high mortality rates. They are predominantly of endogenous origin, however, cross-infection transmitted by healthcare professionals' hands has occurred. The aim of this study was to identify Candida species isolated from the hands of healthcare professionals in a NICU before and after hygiene with 70% ethanol-based gel and evaluate virulence factors DNase, phospholipase, proteinase, hemolysin, biofilm biomass production, and metabolic activity. In vitro antifungal susceptibility testing and similarity by random amplified polymorphic DNA (RAPD) were also performed. C. parapsilosis complex was the most frequent species (57.1%); all isolates presented at least one virulence factor; three isolates (Candida parapsilosis complex) were resistant to amphotericin B, two (Candida famata [currently Debaryomyces hansenii] and Candida guilliermondii [currently Meyerozyma guilliermondii]) was resistant to micafungin, and six (Candida parapsilosis complex, Candida guilliermondii [=Meyerozyma guilliermondii], Candida viswanathi, Candida catenulata [currently Diutina catenulata] and Candida lusitaniae [currently Clavispora lusitaniae]) were resistant to fluconazole. Molecular analysis by RAPD revealed two clusters of identical strains that were in the hands of distinct professionals. Candida spp. were isolated even after hygiene with 70% ethanol-based gel, highlighting the importance of stricter basic measures for hospital infection control to prevent nosocomial transmission.


Assuntos
Antifúngicos , Candida , Infecção Hospitalar , Etanol , Mãos , Testes de Sensibilidade Microbiana , Fatores de Virulência , Humanos , Mãos/microbiologia , Antifúngicos/farmacologia , Fatores de Virulência/genética , Candida/efeitos dos fármacos , Candida/isolamento & purificação , Candida/genética , Candida/patogenicidade , Etanol/farmacologia , Infecção Hospitalar/microbiologia , Infecção Hospitalar/prevenção & controle , Candidíase/microbiologia , Pessoal de Saúde , Técnica de Amplificação ao Acaso de DNA Polimórfico , Biofilmes/efeitos dos fármacos , Biofilmes/crescimento & desenvolvimento , Unidades de Terapia Intensiva Neonatal , Farmacorresistência Fúngica , Géis , Desinfecção das Mãos
9.
Microbiol Spectr ; 12(5): e0425522, 2024 May 02.
Artigo em Inglês | MEDLINE | ID: mdl-38587411

RESUMO

tRNA modifications play important roles in maintaining translation accuracy in all domains of life. Disruptions in the tRNA modification machinery, especially of the anticodon stem loop, can be lethal for many bacteria and lead to a broad range of phenotypes in baker's yeast. Very little is known about the function of tRNA modifications in host-pathogen interactions, where rapidly changing environments and stresses require fast adaptations. We found that two closely related fungal pathogens of humans, the highly pathogenic Candida albicans and its much less pathogenic sister species, Candida dubliniensis, differ in the function of a tRNA-modifying enzyme. This enzyme, Hma1, exhibits species-specific effects on the ability of the two fungi to grow in the hypha morphology, which is central to their virulence potential. We show that Hma1 has tRNA-threonylcarbamoyladenosine dehydratase activity, and its deletion alters ribosome occupancy, especially at 37°C-the body temperature of the human host. A C. albicans HMA1 deletion mutant also shows defects in adhesion to and invasion into human epithelial cells and shows reduced virulence in a fungal infection model. This links tRNA modifications to host-induced filamentation and virulence of one of the most important fungal pathogens of humans.IMPORTANCEFungal infections are on the rise worldwide, and their global burden on human life and health is frequently underestimated. Among them, the human commensal and opportunistic pathogen, Candida albicans, is one of the major causative agents of severe infections. Its virulence is closely linked to its ability to change morphologies from yeasts to hyphae. Here, this ability is linked-to our knowledge for the first time-to modifications of tRNA and translational efficiency. One tRNA-modifying enzyme, Hma1, plays a specific role in C. albicans and its ability to invade the host. This adds a so-far unknown layer of regulation to the fungal virulence program and offers new potential therapeutic targets to fight fungal infections.


Assuntos
Candida albicans , Candidíase , Proteínas Fúngicas , Hifas , RNA de Transferência , Candida albicans/genética , Candida albicans/patogenicidade , Candida albicans/metabolismo , RNA de Transferência/genética , RNA de Transferência/metabolismo , Virulência/genética , Humanos , Proteínas Fúngicas/genética , Proteínas Fúngicas/metabolismo , Candidíase/microbiologia , Hifas/crescimento & desenvolvimento , Hifas/genética , Hifas/metabolismo , Animais , Candida/patogenicidade , Candida/genética , Candida/metabolismo , Interações Hospedeiro-Patógeno , Camundongos , Células Epiteliais/microbiologia
10.
J Proteome Res ; 23(5): 1634-1648, 2024 May 03.
Artigo em Inglês | MEDLINE | ID: mdl-38572994

RESUMO

The delay in making a correct diagnosis of Candida auris causes concern in the healthcare system setting, and immunoproteomics studies are important to identify immunoreactive proteins for new diagnostic strategies. In this study, immunocompetent murine systemic infections caused by non-aggregative and aggregative phenotypes of C. auris and by Candida albicans and Candida haemulonii were carried out, and the obtained sera were used to study their immunoreactivity against C. auris proteins. The results showed higher virulence, in terms of infection signs, weight loss, and histopathological damage, of the non-aggregative isolate. Moreover, C. auris was less virulent than C. albicans but more than C. haemulonii. Regarding the immunoproteomics study, 13 spots recognized by sera from mice infected with both C. auris phenotypes and analyzed by mass spectrometry corresponded to enolase, phosphoglycerate kinase, glyceraldehyde-3-phosphate dehydrogenase, and phosphoglycerate mutase. These four proteins were also recognized by sera obtained from human patients with disseminated C. auris infection but not by sera obtained from mice infected with C. albicans or Aspergillus fumigatus. Spot identification data are available via ProteomeXchange with the identifier PXD049077. In conclusion, this study showed that the identified proteins could be potential candidates to be studied as new diagnostic or even therapeutic targets for C. auris.


Assuntos
Candida , Candidíase , Imunoglobulina G , Animais , Camundongos , Candida/imunologia , Candida/patogenicidade , Humanos , Candidíase/imunologia , Candidíase/microbiologia , Candidíase/sangue , Imunoglobulina G/sangue , Antígenos de Fungos/imunologia , Antígenos de Fungos/sangue , Proteômica/métodos , Candida albicans/imunologia , Candida albicans/patogenicidade , Proteínas Fúngicas/imunologia , Fosfoglicerato Mutase/imunologia , Fosfoglicerato Quinase/imunologia , Gliceraldeído-3-Fosfato Desidrogenases/imunologia , Gliceraldeído-3-Fosfato Desidrogenases/metabolismo , Anticorpos Antifúngicos/sangue , Anticorpos Antifúngicos/imunologia , Feminino , Virulência
11.
Braz. J. Vet. Res. Anim. Sci. (Online) ; 60: e203984, 2023. ilus, tab
Artigo em Inglês | LILACS, VETINDEX | ID: biblio-1518164

RESUMO

Wild animals can be natural reservoirs of different microorganisms, essential for monitoring these pathogens for the generation of knowledge and creation of tools aimed at programs for the prevention and control of infectious diseases, including zoonoses. The objective was to report the fungal diversity in the skin of pacas in captivity in Acre, Western Amazon, Brazil. Twenty-six animals were evaluated, from which skin samples were collected by superficial scraping, hair avulsion, and sterile plastic brush. The samples were seeded on Mycosel agar, and the phenotypic characteristics of the colonies were analyzed. In 80.8% of the samples, different fungi were isolated, from the genera Candida, Microsporum,and Trichophyton, among others. This is the first description of the identification of fungi in the skin of pacas and suggests that these animals can be considered essential reservoirs of saprophytic or pathogenic microorganisms with zoonotic potential in the Western Amazon.(AU)


Animais silvestres podem ser reservatórios naturais de diferentes microrganismos, sendo fundamental o monitoramento destes patógenos para a geração de conhecimento e criação de ferramentas direcionadas a programas de prevenção e controle de enfermidades infecciosas, incluindo as zoonoses. Assim, objetivou-se relatar a diversidade fúngica da pele de pacas criadas em cativeiro no Acre, Amazônia Ocidental, Brasil. Foram avaliados 26 animais, dos quais amostras cutâneas foram colhidas por raspagem superficial, avulsão pilosa e escova plástica estéril. As amostras foram semeadas em ágar Mycosel e as características fenotípicas das colônias foram analisadas. Em 80,8% das amostras houve isolamento de diferentes fungos, dos gêneros Candida, Microsporum e Trichophyton, dentre outros. Esta é a primeira descrição da identificação de fungos na pele de pacas e sugere que estes animais podem ser considerados importantes reservatórios de microrganismos saprófitas ou patogênicos, de potencial zoonótico, na Amazônia Ocidental.(AU)


Assuntos
Animais , Roedores/microbiologia , Infecções Bacterianas e Micoses/diagnóstico , Animais Selvagens/microbiologia , Trichophyton/patogenicidade , Brasil , Candida/patogenicidade , Microsporum/patogenicidade
13.
mBio ; 12(6): e0331721, 2021 12 21.
Artigo em Inglês | MEDLINE | ID: mdl-34903044

RESUMO

Candida species are a leading cause of opportunistic, hospital-associated bloodstream infections with high mortality rates, typically in immunocompromised patients. Several species, including Candida albicans, the most prevalent cause of infection, belong to the monophyletic CUG clade of yeasts. Innate immune cells such as macrophages are crucial for controlling infection, and C. albicans responds to phagocytosis by a coordinated induction of pathways involved in catabolism of nonglucose carbon sources, termed alternative carbon metabolism, which together are essential for virulence. However, the interactions of other CUG clade species with macrophages have not been characterized. Here, we analyzed transcriptional responses to macrophage phagocytosis by six Candida species across a range of virulence and clinical importance. We define a core induced response common to pathogenic and nonpathogenic species alike, heavily weighted to alternative carbon metabolism. One prominent pathogen, Candida parapsilosis, showed species-specific expansion of phagocytosis-responsive genes, particularly metabolite transporters. C. albicans and Candida tropicalis, the other prominent pathogens, also had species-specific responses, but these were largely comprised of functionally uncharacterized genes. Transcriptional analysis of macrophages also demonstrated highly correlated proinflammatory transcriptional responses to different Candida species that were largely independent of fungal viability, suggesting that this response is driven by recognition of conserved cell wall components. This study significantly broadens our understanding of host interactions in CUG clade species, demonstrating that although metabolic plasticity is crucial for virulence in Candida, it alone is not sufficient to confer pathogenicity. Instead, we identify sets of mostly uncharacterized genes that may explain the evolution of pathogenicity. IMPORTANCE Candidiasis is a major fungal infection by Candida species, causing life-threatening invasive disease in immunocompromised patients. C. albicans, which is adapted to commensalism of human mucosae, is the most common cause. While several other species cause infection, most are less prevalent or less virulent. As innate immune cells are the primary defense against Candida infection, we compared the transcriptional responses of C. albicans and related species to phagocytosis by macrophages, to understand the basis of variation in pathogenesis. This response, including the metabolic remodeling required for virulence in C. albicans, was strikingly conserved across the virulence spectrum. Macrophage responses to different species were also highly similar. This study indicates that important elements of host-pathogen interactions in C. albicans are not driven by adaptation to the mammalian host and improves our understanding of pathogenicity in opportunistic fungal species that are understudied but collectively impose a significant threat of their own.


Assuntos
Candida/genética , Candidíase/genética , Candidíase/microbiologia , Interações Hospedeiro-Patógeno , Macrófagos/microbiologia , Candida/classificação , Candida/patogenicidade , Candida/fisiologia , Candidíase/imunologia , Proteínas Fúngicas/genética , Proteínas Fúngicas/metabolismo , Humanos , Macrófagos/imunologia , Viabilidade Microbiana , Fagocitose , Filogenia , Transcriptoma , Virulência
14.
Microb Pathog ; 161(Pt A): 105280, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-34742893

RESUMO

Some studies have demonstrated a high prevalence of Candida species in patients with tuberculosis (TB). This is most likely due to long-term antimicrobial therapy. To date, no longitudinal studies addressed the effects of anti-TB treatment on the fungal burden and virulence of Candida spp. This study investigated the prevalence and virulence of Candida spp. in the oral cavity of 30 TB patients at different stages of treatment through a cohort study. These results were compared with those of 60 systemically healthy individuals in a cross-sectional study. Oral rinse samples from TB patients were collected before 45 and after 120 days of treatment. In the control group, the biological samples were collected only once. Candida spp. were identified by restriction fragment length polymorphism (RFLP) assays, and the following virulence factors were studied: phospholipase C and proteinase production, as well as Candida spp. biofilm and hyphae formation. The clinical diagnosis of TB and its treatment time were associated with the greater fungal burden (p < 0.0001), presence of non-albicans Candida (NAC) species (p = 0.0003), and increased virulence factors when compared with the Candida spp. isolated from systemically healthy individuals. The results showed that anti-TB treatment time was responsible for the increased fungal burden and isolation of NAC in TB patients (p = 0.0233). The increased prevalence, quantification, and virulence of Candida spp. isolated from the oral cavity of TB patients highlight the greater risk of oral lesions and cases of systemic dissemination in these patients.


Assuntos
Antituberculosos , Biofilmes , Candida , Antituberculosos/uso terapêutico , Candida/classificação , Candida/patogenicidade , Estudos de Coortes , Estudos Transversais , Humanos , Boca/microbiologia , Virulência
15.
Gut Microbes ; 13(1): 1993598, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34793277

RESUMO

Antibiotics are commonly used in the Intensive Care Unit (ICU); however, several studies showed that the impact of antibiotics to prevent infection, multi-organ failure, and death in the ICU is less clear than their benefit on course of infection in the absence of organ dysfunction. We characterized here the compositional and metabolic changes of the gut microbiome induced by critical illness and antibiotics in a cohort of 75 individuals in conjunction with 2,180 gut microbiome samples representing 16 different diseases. We revealed an "infection-vulnerable" gut microbiome environment present only in critically ill treated with antibiotics (ICU+). Feeding of Caenorhabditis elegans with Bifidobacterium animalis and Lactobacillus crispatus, species that expanded in ICU+ patients, revealed a significant negative impact of these microbes on host viability and developmental homeostasis. These results suggest that antibiotic administration can dramatically impact essential functional activities in the gut related to immune responses more than critical illness itself, which might explain in part untoward effects of antibiotics in the critically ill.


Assuntos
Antibacterianos/efeitos adversos , Estado Terminal , Microbioma Gastrointestinal/efeitos dos fármacos , Metaboloma/efeitos dos fármacos , Animais , Bactérias/classificação , Bactérias/efeitos dos fármacos , Bactérias/metabolismo , Bactérias/patogenicidade , Ácidos e Sais Biliares/metabolismo , Candida/classificação , Candida/efeitos dos fármacos , Candida/metabolismo , Candida/patogenicidade , Farmacorresistência Fúngica/efeitos dos fármacos , Ácidos Graxos Voláteis/metabolismo , Humanos , Infecções/microbiologia , Unidades de Terapia Intensiva , Mariposas
16.
mBio ; 12(5): e0254821, 2021 10 26.
Artigo em Inglês | MEDLINE | ID: mdl-34663098

RESUMO

We recently discovered a novel form of trained innate immunity (TII) induced by low-virulence Candida species (i.e., Candida dubliniensis) that protects against lethal fungal/bacterial infection. Mice vaccinated by intraperitoneal (i.p.) inoculation are protected against lethal sepsis following Candida albicans/Staphylococcus aureus (Ca/Sa) intra-abdominal infection (IAI) or Ca bloodstream infection (BSI). The protection against IAI is mediated by long-lived Gr-1+ leukocytes as putative myeloid-derived suppressor cells (MDSCs) and not by prototypical trained macrophages. This study aimed to determine if a similar TII mechanism (Gr-1+ cell-mediated suppression of sepsis) is protective against BSI and whether this TII can also be induced following intravenous (i.v.) vaccination. For this, mice were vaccinated with low-virulence Candida strains (i.p. or i.v.), followed by lethal challenge (Ca/Sa i.p. or Ca i.v.) 14 days later, and observed for sepsis (hypothermia, sepsis scoring, and serum cytokines), organ fungal burden, and mortality. Similar parameters were monitored following depletion of macrophages or Gr-1+ leukocytes during lethal challenge. The results showed that mice vaccinated i.p. or i.v. were protected against lethal Ca/Sa IAI or Ca BSI. In all cases, protection was mediated by Ly6G+ Gr-1+ putative granulocytic MDSCs (G-MDSCs), with no role for macrophages, and correlated with reduced sepsis parameters. Protection also correlated with reduced fungal burden in spleen and brain but not liver or kidney. These results suggest that Ly6G+ G-MDSC-mediated TII is induced by either the i.p. and i.v. route of inoculation and protects against IAI or BSI forms of systemic candidiasis, with survival correlating with amelioration of sepsis and reduced organ-specific fungal burden. IMPORTANCE Trained innate immunity (TII) is induced following immunization with live attenuated microbes and represents a clinically important strategy to enhance innate defenses. TII was initially demonstrated following intravenous inoculation with low-virulence Candida albicans, with protection against a subsequent lethal C. albicans intravenous bloodstream infection (BSI) mediated by monocytes with enhanced cytokine responses. We expanded this by describing a novel form of TII induced by intraperitoneal inoculation with low-virulence Candida that protects against lethal sepsis induced by polymicrobial intra-abdominal infection (IAI) via Gr-1+ leukocytes as putative myeloid-derived suppressor cells (MDSCs). In this study, we addressed these two scenarios and confirmed an exclusive role for Ly6G+ Gr-1+ leukocytes in mediating TII against either IAI or BSI via either route of inoculation, with protection associated with suppression of sepsis. These studies highlight the previously unrecognized importance of Ly6G+ MDSCs as central mediators of a novel form of TII termed trained tolerogenic immunity.


Assuntos
Antígenos Ly/imunologia , Candida/imunologia , Candidíase/imunologia , Candidíase/prevenção & controle , Imunidade Inata , Leucócitos/imunologia , Receptores de Quimiocinas/imunologia , Vacinação/métodos , Animais , Candida/patogenicidade , Modelos Animais de Doenças , Feminino , Camundongos , Infecções Estafilocócicas/imunologia , Infecções Estafilocócicas/prevenção & controle , Virulência
17.
PLoS One ; 16(10): e0258108, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34614005

RESUMO

Candida is an opportunistic pathogen and a common cause of fungal infections worldwide. Anti-fungal use against Candida infections has resulted in the appearance of resistant strains. The limited choice of anti-fungal therapy means alternative strategies are needed to control fungal infectious diseases. The aim of this study was to evaluate the inhibition of Candida biofilm formation by Hedera rhombea (Korean name: songak) extract. Biofilm formation was assessed using the crystal violet assay which showed a dose dependent reduction in the presence of extract with the biofilm formation inhibitory concentration of C. albicans (IC50 = 12.5µg/ml), C. tropicalis var. tropicalis (IC50 = 25µg/ml), C. parapsilosis var. parapsilosis (IC50 = 6.25µg/ml), C. glabrata (IC50 = 6.25µg/ml), C. tropicalis (IC50 = 12.5µg/ml), and C. parapsilosis (IC50 = 12.5µg/ml) without directly reducing Candida growth. Treatment with 6.25µg/mL of extract increased the antifungal susceptibility to miconazole from 32% decreasing of fungal growth to 98.8% of that based on the fungal growth assay. Treatment of extract dose-dependently reduced the dimorphic transition of Candida based on the dimorphic transition assay and treatment of 3.125µg/mL of extract completely blocked the adherence of Candida to the HaCaT cells. To know the molecular mechanisms of biofilm formation inhibition by extract, qRT-PCR analysis was done, and the extract was found to dose dependently reduce the expression of hyphal-associated genes (ALS3, ECE1, HWP1, PGA50, and PBR1), extracellular matrix genes (GSC1, ZAP1, ADH5, and CSH1), Ras1-cAMP-PKA pathway genes (CYR1, EFG1, and RAS1), Cph2-Tec1 pathway gene (TEC1) and MAP kinases pathway gene (HST7). In this study, Hedera rhombea extract showed inhibition of fungal biofilm formation, activation of antifungal susceptibility, and reduction of infection. These results suggest that fungal biofilm formation is good screen for developing the antifungal adjuvant and Hedera rhombea extract should be a good candidate against biofilm-related fungal infection.


Assuntos
Antifúngicos/farmacologia , Candida/efeitos dos fármacos , Candidíase/tratamento farmacológico , Hedera/química , Antifúngicos/química , Biofilmes/efeitos dos fármacos , Candida/genética , Candida/patogenicidade , Candidíase/genética , Candidíase/microbiologia , Farmacorresistência Fúngica/efeitos dos fármacos , Proteínas Fúngicas/genética , Regulação Fúngica da Expressão Gênica/efeitos dos fármacos , Humanos , Hifas/química , Testes de Sensibilidade Microbiana
18.
Biomed Res Int ; 2021: 5548746, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34545329

RESUMO

OBJECTIVE: The objective of this study was to determine the candidal load of the patients with Chronic Obstructive Pulmonary Disease (COPD) and evaluate the oral health status of subjects with COPD. Material and Methods. N = 112 COPD subjects and N = 100 control subjects were included in the study. The selection of COPD cases was confirmed based on the set criteria from the American College of Physicians. The oral health status was assessed as per WHO criteria to determine the score of decayed, missing, and filled teeth (DMFT), significant caries index (SiC), community periodontal index and treatment needs (CPITN), and oral hygiene index-simplified (OHI-S). Gram staining was performed to identify Candida using the whole saliva. Quantitative evaluation of the candidal load was carried out using Sabouraud Dextrose Agar (SDA). Chrome agar was used to differentiate between the commensal carriages. A statistical analysis paired t-test and 95% confidence interval (CI) for proportions was carried out using STATA software. RESULTS: Candidal growth was found in 21.42% (n = 24) of COPD cases and 1.1% (n = 11) of control cases (p < 0.05) (95% CI 0.45, 0.59). The DMFT score was 8.26 in COPD subjects and 4.6 in controls, the SiC score was 16.42 in COPD subjects and 10.25 in controls, and the CPITN score for both COPD and control cases was score 2. CONCLUSION: In conclusion, there was a higher candidal load among subjects suffering from COPD. Theophylline medication can be a risk factor for increased candidal load in COPD patients.


Assuntos
Candidíase Bucal/diagnóstico , Candidíase Bucal/microbiologia , Doença Pulmonar Obstrutiva Crônica/microbiologia , Adulto , Idoso , Candida/patogenicidade , Estudos de Casos e Controles , Estudos de Coortes , Estudos Transversais , Cárie Dentária/microbiologia , Feminino , Nível de Saúde , Humanos , Masculino , Pessoa de Meia-Idade , Saúde Bucal/tendências , Higiene Bucal , Índice de Higiene Oral , Índice Periodontal , Doença Pulmonar Obstrutiva Crônica/metabolismo , Doença Pulmonar Obstrutiva Crônica/fisiopatologia , Fatores de Risco
19.
Molecules ; 26(15)2021 Jul 28.
Artigo em Inglês | MEDLINE | ID: mdl-34361723

RESUMO

Genito-urinary tract infections have a high incidence in the general population, being more prevalent among women than men. These diseases are usually treated with antibiotics, but very frequently, they are recurrent and lead to the creation of resistance and are associated with increased morbidity and mortality. For this reason, it is necessary to develop new compounds for their treatment. In this work, our objective is to review the characteristics of the compounds of a new formulation called Itxasol© that is prescribed as an adjuvant for the treatment of UTIs and composed of ß-arbutin, umbelliferon and n-acetyl cysteine. This formulation, based on biomimetic principles, makes Itxasol© a broad-spectrum antibiotic with bactericidal, bacteriostatic and antifungal properties that is capable of destroying the biofilm and stopping its formation. It also acts as an anti-inflammatory agent, without the adverse effects associated with the recurrent use of antibiotics that leads to renal nephrotoxicity and other side effects. All these characteristics make Itxasol© an ideal candidate for the treatment of UTIs since it behaves like an antibiotic and with better characteristics than other adjuvants, such as D-mannose and cranberry extracts.


Assuntos
Acetilcisteína/uso terapêutico , Arbutina/uso terapêutico , Produtos Biológicos/uso terapêutico , Umbeliferonas/uso terapêutico , Infecções Urinárias/tratamento farmacológico , Acetilcisteína/química , Antibacterianos/química , Antibacterianos/uso terapêutico , Anti-Inflamatórios/química , Anti-Inflamatórios/uso terapêutico , Antifúngicos/química , Antifúngicos/uso terapêutico , Arbutina/química , Biofilmes/efeitos dos fármacos , Biofilmes/crescimento & desenvolvimento , Produtos Biológicos/química , Materiais Biomiméticos/química , Materiais Biomiméticos/uso terapêutico , Candida/efeitos dos fármacos , Candida/crescimento & desenvolvimento , Candida/patogenicidade , Combinação de Medicamentos , Feminino , Bactérias Gram-Negativas/efeitos dos fármacos , Bactérias Gram-Negativas/crescimento & desenvolvimento , Bactérias Gram-Negativas/patogenicidade , Bactérias Gram-Positivas/efeitos dos fármacos , Bactérias Gram-Positivas/crescimento & desenvolvimento , Bactérias Gram-Positivas/patogenicidade , Humanos , Masculino , Testes de Sensibilidade Microbiana , Umbeliferonas/química , Infecções Urinárias/microbiologia , Infecções Urinárias/patologia
20.
Molecules ; 26(16)2021 Aug 09.
Artigo em Inglês | MEDLINE | ID: mdl-34443400

RESUMO

The search for coatings that extend the useful life of biomedical devices has been of great interest, and titanium has been of great relevance due to its innocuousness and low reactivity. This study contributes to the investigation of Ti/Ag films in different configurations (monolayer and multilayer) deposited by magnetron sputtering. The sessile droplet technique was applied to study wettability; greater film penetrability was obtained when Ag is the external layer, conferring high efficiency in cell adhesion. The morphological properties were characterized by SEM, which showed porous nuclei on the surface in the Ag coating and crystals embedded in the Ti film. The structural properties were studied by XRD, revealing the presence of TiO2 in the anatase crystalline phase in a proportion of 49.9% and the formation of a silver cubic network centered on the faces. Tafel polarization curves demonstrated improvements in the corrosion current densities of Ag/Ti/Ag/Ti/Ag/Ti/Ag/Ti and Ti/Ag compared to the Ag coating, with values of 0.1749, 0.4802, and 2.044 nA.m-2, respectively. Antimicrobial activity was evaluated against the bacteria Pseudomonas aeruginosa and Bacillus subtilis and the yeasts Candida krusei and Candida albicans, revealing that the Ti/Ag and Ag/Ti/Ag/Ti/Ag/Ti/Ag/Ti coatings exhibit promise in biomedical material applications.


Assuntos
Materiais Revestidos Biocompatíveis/química , Prata/farmacologia , Titânio/farmacologia , Molhabilidade/efeitos dos fármacos , Anti-Infecciosos/química , Anti-Infecciosos/farmacologia , Bacillus subtilis/efeitos dos fármacos , Bacillus subtilis/patogenicidade , Candida/efeitos dos fármacos , Candida/patogenicidade , Materiais Revestidos Biocompatíveis/farmacologia , Humanos , Teste de Materiais , Pichia/efeitos dos fármacos , Pichia/patogenicidade , Pseudomonas aeruginosa/efeitos dos fármacos , Pseudomonas aeruginosa/patogenicidade , Prata/química , Propriedades de Superfície , Titânio/química
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