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Clinical Microbiology and Infection :... Jul 2019Recently there has been an increase in Candida infections worldwide. A handful of species in the genus Candida are opportunistic pathogens and have been known to cause... (Review)
Review
BACKGROUND
Recently there has been an increase in Candida infections worldwide. A handful of species in the genus Candida are opportunistic pathogens and have been known to cause infections in immunocompromised or otherwise impaired hosts. These infections can be superficial, affecting the skin or mucous membrane, or invasive, which can be life-threatening. Azoles and echinocandins are antifungal drugs used globally to treat Candida infections. However, resistance to these antifungal drugs has increased in many of the Candida species, and the effects this has in the clinical setting can be seen.
OBJECTIVES
Here, we discuss the mechanisms that Candida albicans, Candida dubliniensis, Candida glabrata, Candida parapsilosis, Candida tropicalis and Candida auris are implementing to increase resistance to azoles and echinocandins, and how they are affecting clinical, or hospital, settings worldwide.
SOURCES
Different studies and papers describing the mechanisms of antifungal drugs and Candida species evolution to becoming resistant to these drugs were looked at for this review.
CONTENT
We discuss the mechanisms that azoles and echinocandins use against Candida species to treat infections, as well as the evolution of these fungi to become resistant to these drugs, and the effect this has in the clinical settings around the globe.
IMPLICATIONS
Increased resistance to azoles and echinocandins by Candida species is an increasingly serious problem in clinical settings worldwide. Understanding the mechanisms used against antifungal drugs is imperative for patient treatment.
Topics: Antifungal Agents; Azoles; Candida; Candida albicans; Candida glabrata; Drug Resistance, Multiple, Fungal; Echinocandins; Humans; Microbial Sensitivity Tests
PubMed: 30965100
DOI: 10.1016/j.cmi.2019.03.028 -
JAMA Neurology Aug 2018Identifying infectious causes of subacute or chronic meningitis can be challenging. Enhanced, unbiased diagnostic approaches are needed.
IMPORTANCE
Identifying infectious causes of subacute or chronic meningitis can be challenging. Enhanced, unbiased diagnostic approaches are needed.
OBJECTIVE
To present a case series of patients with diagnostically challenging subacute or chronic meningitis using metagenomic next-generation sequencing (mNGS) of cerebrospinal fluid (CSF) supported by a statistical framework generated from mNGS of control samples from the environment and from patients who were noninfectious.
DESIGN, SETTING, AND PARTICIPANTS
In this case series, mNGS data obtained from the CSF of 94 patients with noninfectious neuroinflammatory disorders and from 24 water and reagent control samples were used to develop and implement a weighted scoring metric based on z scores at the species and genus levels for both nucleotide and protein alignments to prioritize and rank the mNGS results. Total RNA was extracted for mNGS from the CSF of 7 participants with subacute or chronic meningitis who were recruited between September 2013 and March 2017 as part of a multicenter study of mNGS pathogen discovery among patients with suspected neuroinflammatory conditions. The neurologic infections identified by mNGS in these 7 participants represented a diverse array of pathogens. The patients were referred from the University of California, San Francisco Medical Center (n = 2), Zuckerberg San Francisco General Hospital and Trauma Center (n = 2), Cleveland Clinic (n = 1), University of Washington (n = 1), and Kaiser Permanente (n = 1). A weighted z score was used to filter out environmental contaminants and facilitate efficient data triage and analysis.
MAIN OUTCOMES AND MEASURES
Pathogens identified by mNGS and the ability of a statistical model to prioritize, rank, and simplify mNGS results.
RESULTS
The 7 participants ranged in age from 10 to 55 years, and 3 (43%) were female. A parasitic worm (Taenia solium, in 2 participants), a virus (HIV-1), and 4 fungi (Cryptococcus neoformans, Aspergillus oryzae, Histoplasma capsulatum, and Candida dubliniensis) were identified among the 7 participants by using mNGS. Evaluating mNGS data with a weighted z score-based scoring algorithm reduced the reported microbial taxa by a mean of 87% (range, 41%-99%) when taxa with a combined score of 0 or less were removed, effectively separating bona fide pathogen sequences from spurious environmental sequences so that, in each case, the causative pathogen was found within the top 2 scoring microbes identified using the algorithm.
CONCLUSIONS AND RELEVANCE
Diverse microbial pathogens were identified by mNGS in the CSF of patients with diagnostically challenging subacute or chronic meningitis, including a case of subarachnoid neurocysticercosis that defied diagnosis for 1 year, the first reported case of CNS vasculitis caused by Aspergillus oryzae, and the fourth reported case of C dubliniensis meningitis. Prioritizing metagenomic data with a scoring algorithm greatly clarified data interpretation and highlighted the problem of attributing biological significance to organisms present in control samples used for metagenomic sequencing studies.
Topics: Adolescent; Adult; Animals; Aspergillus oryzae; Candida; Candidiasis; Child; Chronic Disease; Cryptococcus neoformans; Female; HIV Infections; HIV-1; High-Throughput Nucleotide Sequencing; Histoplasma; Histoplasmosis; Humans; Male; Meningitis; Meningitis, Cryptococcal; Metagenome; Metagenomics; Middle Aged; Neuroaspergillosis; Neurocysticercosis; Sequence Analysis, RNA; Taenia solium; Young Adult
PubMed: 29710329
DOI: 10.1001/jamaneurol.2018.0463 -
International Journal of Microbiology 2022This study aims to evaluate the association of and with periodontitis in adolescents and young adults in a Moroccan population.
AIM
This study aims to evaluate the association of and with periodontitis in adolescents and young adults in a Moroccan population.
METHODS
426 subjects aged between 12 and 25 years were recruited for the study. A pool of plaque sample was taken. Samples were cultured on Sabouraud Chloramphenicol medium at 37°C for 24-48 hours and then identified by the Vitek 2 YST system. Clinical data and presence of and were analyzed using Jamovi (Version 1.8).
RESULTS
was observed in 25 subjects among 68 diseased patients (37%) and in 60 subjects among 358 healthy patients (17%). It can be reported that under normal yeast conditions, there is a statistically significant difference between these two groups ( < 0.001). was more prevalent in periodontitis than in healthy subjects (=0.026). Regarding clinical variables, subgroups of periodontitis subjects showed significant statistical differences for periodontal probing depth, clinical attachment loss, and number of decayed teeth in advanced periodontitis in comparison with initial or mild periodontitis. The results also indicate that the presence of the two species of is not related to gender or age ( > 0.05) nor related to the severity of the periodontal disease in this population.
CONCLUSION
Within the limits of our study, is more frequently associated with periodontitis. The potential role of in periodontitis pathogenesis is very complex. More studies on biofilm associated with different forms of periodontitis are necessary. It is also important to assess the coexistence of periodontitis and caries and the associated biofilms.
PubMed: 35058983
DOI: 10.1155/2022/4625368 -
Journal of Clinical Microbiology Nov 1997
Topics: Candida; Genotype; Geography; Phenotype; Terminology as Topic
PubMed: 9350785
DOI: 10.1128/jcm.35.11.3011-3012.1997 -
Frontiers in Cellular and Infection... 2022Severe Early Childhood Caries (sECC) is a multifactorial disease associated with the occurrence of specific oral microorganisms and other environmental, behavioral, and...
Severe Early Childhood Caries (sECC) is a multifactorial disease associated with the occurrence of specific oral microorganisms and other environmental, behavioral, and genetic factors. This study aimed to construct a multivariable model including the occurrence of spp. and selected behavioral factors (length of breastfeeding, serving sweet beverages and beginning of brushing child's teeth) to determine their relationships to the occurrence of sECC. In this case-control study 164 children with sECC and 147 children without dental caries were included. MALDI-TOF MS and multiplex qPCR were used to identify spp. and selected bacteria in dental plaque samples, respectively. A questionnaire on oral hygiene, diet, and children's health was filled in by the parents. The constructed multivariable logistic regression model showed an independent influence of the microbial and behavioral factors in sECC etiopathogenesis. The occurrence of and was associated with higher odds of sECC development (odds ratio, OR: 9.62 and 16.93, respectively), together with breastfeeding of 6 months or less (OR: 2.71), exposure to sweet beverages (OR: 3.77), and starting to brush child's teeth after the 12 month of age (OR: 4.10), all statistically significant ( < 0.01). Considering the high occurrence of and in dental plaque in children with sECC, we propose them as "keystone pathogens" and risk factors for sECC. The models showed that presence of specific species of in dental plaque may be a better descriptor of sECC than the mentioned behavioral factors.
Topics: Candida; Candida albicans; Case-Control Studies; Child; Child, Preschool; Dental Caries; Dental Caries Susceptibility; Dental Plaque; Humans; Streptococcus mutans
PubMed: 35959372
DOI: 10.3389/fcimb.2022.943480 -
PloS One 2022Fungal agglutinin-like sequence (Als) cell-surface glycoproteins, best characterized in Candida albicans, mediate adhesive and aggregative interactions with host cells,...
Fungal agglutinin-like sequence (Als) cell-surface glycoproteins, best characterized in Candida albicans, mediate adhesive and aggregative interactions with host cells, other microbes, and abiotic surfaces. Monoclonal antibodies (MAbs) specific for each C. albicans Als protein are valuable reagents for gaining insight into Als protein localization and function. This manuscript describes development and validation of MAbs specific for C. albicans Als2, as well as for C. albicans Als9-1 and Als9-2, two protein variants produced from the ALS9 locus. Native C. albicans ALS9 expression levels were not sufficiently high to produce detectable Als9 protein on the wild-type cell surface so MAb validation required production of overexpression strains, each featuring one of the two ALS9 alleles. An anti-Als2 MAb was raised against an N-glycosylated form of the protein immunogen, as well as an Endoglycosidase H-treated immunogen. The MAb raised against the N-glycosylated immunogen proved superior and immunolabeled C. albicans yeast cells and germ tubes, and the surface of Candida dubliniensis and Candida tropicalis yeasts. Als2 was visible on C. albicans yeast cells recovered from a murine model of oral candidiasis, demonstrating Als2 production both in vivo and in vitro. These new MAbs add to the collection of anti-Als MAbs that are powerful tools to better understand the role of Als proteins in C. albicans biology and pathogenesis.
Topics: Agglutinins; Animals; Antibodies, Monoclonal; Candida albicans; Candidiasis, Oral; Fungal Proteins; Mice
PubMed: 35802580
DOI: 10.1371/journal.pone.0269681 -
International Journal of Implant... Jun 2021Candida is a heterogeneous fungal genus. Subgingival sulcus is a refuge for Candida, which has already been related to the pathogenic inflammation of periodontitis. This... (Review)
Review
BACKGROUND
Candida is a heterogeneous fungal genus. Subgingival sulcus is a refuge for Candida, which has already been related to the pathogenic inflammation of periodontitis. This work aims to review the presence of Candida in the sulcular fluid surrounding dental implants and discuss its potential role in peri-implantitis.
RESULTS
A bibliographical research was performed in PubMed, Scopus and Web of Science databases, with the keywords candida, peri-implantitis, periimplantitis, "dental implant" and implant. Newcastle-Ottawa Scale was used to assess the methodological quality of the included studies. At the end, nine observational studies were included, which analysed 400 dental implants with PI and 337 without peri-implantitis. Presence of Candida was assessed by traditional microbiological culture in blood agar or/and CHROMagar, though identification was also detected by quantitative real-time PCR, random amplified polymorphic DNA or ATB ID 32C. Dentate individuals and implants with peri-implantitis (range, 3-76.7%) had a bigger presence of Candida. C. albicans was the most isolated species, followed by Candida parapsilosis, Candida tropicalis, and Candida dubliniensis.
CONCLUSION
Candida is part of the microbiological profile of the peri-implant sulcular fluid. More studies are needed to compare the link between Candida and other microorganisms and to discover the true role of these fungi in peri-implantitis.
Topics: Candida; Candida albicans; Humans; Peri-Implantitis; Periodontitis
PubMed: 34136968
DOI: 10.1186/s40729-021-00338-7 -
Frontiers in Cellular and Infection... 2022The cell-surface protein Hwp1 functions in adhesion to the host and in biofilm formation. A peptide from the Gln-Pro-rich adhesive domain of Hwp1 was used to raise...
The cell-surface protein Hwp1 functions in adhesion to the host and in biofilm formation. A peptide from the Gln-Pro-rich adhesive domain of Hwp1 was used to raise monoclonal antibody (MAb) 2-E8. MAb 2-E8 specificity for Hwp1 was demonstrated using a isolate and strains that expressed at least one allele. Immunofluorescence and atomic force microscopy experiments using MAb 2-E8 confirmed germ-tube-specific detection of the Hwp1 protein. MAb 2-E8 also immunolabeled the tips of some germ tubes grown under conditions that maximized expression. The phylogeny of and closely related genes suggested that the Gln-Pro-rich adhesive domain was unique to and focusing the utility of MAb 2-E8 on these species. This new reagent can be used to address unanswered questions about Hwp1 and its interactions with other proteins in the context of biology and pathogenesis.
Topics: Antibodies, Monoclonal; Candida; Candida albicans; Fungal Proteins; Membrane Glycoproteins; Membrane Proteins
PubMed: 35832385
DOI: 10.3389/fcimb.2022.907453 -
AIMS Microbiology 2020species cause a wide spectrum of disease entities. and -members of complex-are currently gaining both clinical and epidemiologic significance.
BACKGROUND
species cause a wide spectrum of disease entities. and -members of complex-are currently gaining both clinical and epidemiologic significance.
MATERIALS AND METHODS
Totally, 150 pediatric isolates that had previously been identified as species complex based on a positive germ tube test were included. The isolates were cultured on CHROMagar medium to ensure their purity and the results of germ tube test. For definitive speciation, PCR amplification and size polymorphism of the () gene was used. The results of -PCR were confirmed by sequencing the amplified fragments for randomly selected isolates of and .
RESULTS
All 150 isolates included in this study were reconfirmed as complex on chromogenic media. Based on the gene size polymorphism, 141 (94%) isolates were identified as , 2 (1.33%) as , and 1 (0.67%) as . The remaining 6 (4%) complex isolates were a mix of and . All isolates of and have been recovered from cases of candiduria.
CONCLUSION
, either alone or mixed with , could be a cause of candiduria among pediatric patients and should not be ignored.
PubMed: 33134744
DOI: 10.3934/microbiol.2020017 -
Microbiology Spectrum Dec 2022To understand the changes of resistance in clinically commonly encountered fungi, we used the Antimicrobial Testing Leadership and Surveillance (ATLAS) database to...
Susceptibilities of Worldwide Isolates of Intrapulmonary Species and Important Species in Sterile Body Sites against Important Antifungals: Data from the Antimicrobial Testing Leadership and Surveillance Program, 2017-2020.
To understand the changes of resistance in clinically commonly encountered fungi, we used the Antimicrobial Testing Leadership and Surveillance (ATLAS) database to explore antifungal susceptibilities against clinically important isolates of and species (collected from intrapulmonary and sterile body areas, respectively). We applied the CLSI antifungal 2020 and the EUCAST antifungal 2020 guidelines. From 2017 to 2020, isolates of intrapulmonary Aspergillus fumigatus ( = 660), Aspergillus niger ( = 107), Aspergillus flavus ( = 96), Aspergillus terreus ( = 40), and Aspergillus nidulans species complex ( = 26) and sterile site-originated isolates of Candida albicans ( = 1,810), Candida glabrata ( = 894), Candida krusei ( = 120), Candida dubliniensis ( = 107), Candida lusitaniae ( = 82), Candida guilliermondii ( = 28), and Candida auris ( = 7) were enrolled in this study. Using the EUCAST 2020 breakpoints, it was demonstrated that amphotericin B and posaconazole displayed poor susceptibility rates against A. fumigatus isolates (<50% and 18.9%, respectively). In contrast, isavuconazole and itraconazole showed high potency against most isolates (>92%). Most intrapulmonary isolates exhibited MICs of ≤0.06 μg/mL to anidulafungin. Furthermore, intrapulmonary A. fumigatus isolates collected from Italy and the United Kingdom exhibited lower susceptibility to isavuconazole (72.2% and 69%, respectively) than those in the remaining ATLAS participant countries (>85%). Higher isavuconazole MICs against C. auris and C. guilliermondii (1 and 4 μg/mL, respectively) were observed compared to the other five species. Despite the aforementioned MICs and susceptibilities against fungi, research needs to consider the pharmacokinetic (PK) profiles, pharmacodynamic (PD) parameters, and clinical treatment experience with antifungals against specific species. In addition to monitoring the antifungal susceptibilities of clinically important fungi, reviewing the PK/PD indices and the clinical therapy experience of antifungals under evaluation are important to guide an appropriate antifungal prescription. The efficacies of liposomal amphotericin B complex and anidulafungin for the treatment of pulmonary aspergillosis caused by different species need to be periodically evaluated in the future.
Topics: Anidulafungin; Antifungal Agents; Aspergillus; Candida; Drug Resistance, Fungal; Microbial Sensitivity Tests
PubMed: 36314941
DOI: 10.1128/spectrum.02965-22