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Relative risk (RR) of coccidioidomycosis based on race. a

Relative risk (RR) of coccidioidomycosis based on race. a

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Article
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The incidence of invasive mycoses is increasing, especially among patients who are immunocompromised or hospitalized with serious underlying diseases. Such infections may be broken into two broad categories: opportunistic and endemic. The most important agents of the opportunistic mycoses are Candida spp., Cryptococcus neoformans, Pneumocystis jiro...

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... These Candida species are the most common human fungal pathogens, and cause (i) superficial infections on both skin and mucosal surfaces, which may be unpleasant but are relatively innocuous; however superficial infections can potentially impair an individual's quality of life, and (ii) systemic infections resulting from the dissemination of the fungus through the bloodstream. 2 In this context, it is known that systemic infections are lifethreatening, as their mortality rates are greater than 40%. 3 Clinical Candida infection rates increase yearly 4,5 due to the increasing number of newly-diagnosed immunocompromised patients, 6 the widespread utilization of solid organ transplantation to treat organ failure, 7 and the extensive and routine use of immunosuppressant drugs and broad-spectrum antibiotics, particularly in cancer chemotherapy. ...
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Candida albicans (C. albicans) is a ubiquitous fungal commensal component of the human microbiota, and under certain circumstances, such as during an immunocompromised state, it may initiate different types of infection. Moreover, C. albicans continuously and reciprocally interacts with the host immune system as well as with other elements of the gut microbiota, thus contributing significantly to both gut homeostasis and host immunity. People living with HIV (PLWH), including those receiving antiretroviral therapy, are characterized by a depletion of CD4 + T-cells and dysbiosis in their gut. C. albicans colonization is frequent in PLWH, causing both a high prevalence and high morbidity. Gut barrier damage and elevated levels of microbial translocation are also fairly common in this population. Herein, we take a closer look at the reciprocity among C. albicans, gut microbiota, HIV, and the host immune system, thus throwing some light on this complex interplay.
... The polymorphic fungus Candida albicans is a member of the normal human microbiome, but under certain circumstances, especially among immunocompromised populations, it causes infections that range from superficial infections of the skin to life-threatening systemic infections in the bloodstream or internal organs [6]. Candida is the fourth most common cause of hospital-acquired systemic infections in the United States, with crude mortality rates of up to 50% [7]. Treatment for these fungal infections has adverse effects and is slowly becoming obsolete due to varying mutation rates and rising resistance in multiple species. ...
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It has now been proven that many pathogens that cause infections and inflammation gradually mutate and become resistant to antibiotics. Chemically synthesized drugs treating inflammation most often only affect symptoms, but side effects could lead to the failure of human organs’ functionality. On the other hand, plant-derived natural compounds have a long-term healing effect. It was shown that sea buckthorn (SBT) twigs are a rich source of biologically active compounds, including oligomeric proanthocyanidins (PACs). This study aimed to assess the anti-pathogenic and anti-inflammatory activity of water/ethanol extracts and PACs obtained from the lignocellulosic biomass of eight SBT cultivars. The anti-pathogenic activity of extracts and PACs was studied against pathogenic bacteria Pseudomonas aeruginosa, Staphylococcus aureus, Escherichia coli, Bacillus cereus and fungus Candida albicans in 96-well plates by the two-fold serial broth microdilution method. The anti-bacterial activity of purified PACs was 4 and 10 times higher than for water and water/ethanol extracts, respectively, but the extracts had higher anti-fungal activity. Purified PACs showed the ability to reduce IL-8 and IL-6 secretion from poly-I:C-stimulated peripheral blood mononuclear cells. For the extracts and PACs of SBT cultivar ‘Maria Bruvele’ in the concentration range 0.0313–4.0 mg/mL, no toxic effect was observed.
... The use of metabolomics approach in the field of microbiology has gained immense attraction in recent years (Xu et al. 2014). This field of study can be used effectively in understanding the microbial structure and difference in metabolomics between the planktonic and sessile cells, thereby providing a better understanding on polymicrobial biofilm (Pfaller and Diekema 2010). Quantification of various types of metabolites associated with the biological systems can be analyzed by the use of metabolome analysis (Takahashi et al. 2012). ...
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The ocean is a treasure trove of both living and nonliving creatures, harboring incredibly diverse group of organisms. A plethora of marine sourced bioactive compounds are discovered over the past few decades, many of which are found to show antibiofilm activity. These are of immense clinical significance since the formation of microbial biofilm is associated with the development of high antibiotic resistance. Biofilms are also responsible to bring about problems associated with industries. In fact, the toilets and wash-basins also show degradation due to development of biofilm on their surfaces. Antimicrobial resistance exhibited by the biofilm can be a potent threat not only for the health care unit along with industries and daily utilities. Various recent studies have shown that the marine members of various kingdom are capable of producing antibiofilm compounds. Many such compounds are with unique structural features and metabolomics approaches are essential to study such large sets of metabolites. Associating holobiome metabolomics with analysis of their chemical attribute may bring new insights on their antibiofilm effect and their applicability as a substitute for conventional antibiotics. The application of computer-aided drug design/discovery (CADD) techniques including neural network approaches and structured-based virtual screening, ligand-based virtual screening in combination with experimental validation techniques may help in the identification of these molecules and evaluation of their drug like properties.
... Hartmann's solutions, commonly used intravenously after trauma, surgery, or burn injury (Pfaller & Diekema, 2010). It is found that the usage of lactate-containing solutions after surgery increases the risk of systemic candidiasis and the formation of biofilms in catheters, representing a severe problem in modern medicine (Donelli & Vuotto, 2014). ...
Article
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Candida albicans is a normal resident of humans and also a prevalent fungal pathogen. Lactate, a nonfermentative carbon source available in numerous anatomical niches, can be used by C. albicans as a carbon source. However, the key regulator(s) involved in this process remain unknown. Here, through a genetic screen, we report the identification of a transcription factor Zcf24 that is specifically required for the lactate utilization in C. albicans. Zcf24 is responsible for the induction of CYB2, a gene encoding lactate dehydrogenase that is essential for lactate catabolism, in response to lactate. Chromatin immunoprecipitation showed a significantly higher signal of Zcf24 on CYB2 promoter in lactate‐grown cells than that in glucose‐grown cells. Genome‐wide transcription profiling indicates that, in addition to CYB2, Zcf24 regulates genes involved in the β‐oxidation of fatty acids, iron transport and drug transport. Surprisingly, deleting ZCF24 confers the enhanced commensal fitness. This could be attributed to Crz1‐activated β‐glucan masking in zcf24 mutant. The orthologs of Zcf24 are distributed in species most closely to C. albicans and some filamentous fungal species. Altogether, Zcf24 is the first transcription factor identified to date that regulates lactate catabolism in C. albicans and it is also involved in the regulation of commensalism. Candida albicans not only assimilates lactate to support growth and colonization, but also exploits this carboxylic acid to induce β‐glucan masking, thereby establishing immune evasion. We found that a zinc‐finger transcription factor Zcf24 is essential for lactate utilization in C. albicans via inducing the expression of CYB2 that encodes a lactate dehydrogenase. Zcf24 also exerts its inhibitory role in commensal fitness possibly through modulating lactate‐induced changes in cell wall architecture.
... Genome plasticity-the ability to generate large-scale genomic variation-is emerging as a critical adaptive mechanism in human microbial pathogens that need to adapt quickly to extreme environmental shifts because it provides genetic diversity upon which selection can act [4][5][6][7][8]. One such organism is Candida albicans, a common human fungal pathogen and a prevalent cause of death due to systemic fungal infections [9]. C. albicans is part of the normal microbiota of most healthy individuals but, in immunocompromised individuals, it is a dangerous pathogen causing a wide range of infections, including life-threatening disseminated diseases [10]. ...
... C. albicans is part of the normal microbiota of most healthy individuals but, in immunocompromised individuals, it is a dangerous pathogen causing a wide range of infections, including life-threatening disseminated diseases [10]. Azole antifungal agents, such as fluconazole (FLC), are the most commonly prescribed drugs for treating C. albicans infections [9,11,12]. ...
Article
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A delicate balance between genome stability and instability ensures genome integrity while generating genetic diversity, a critical step for evolution. Indeed, while excessive genome instability is harmful, moderated genome instability can drive adaptation to novel environments by maximising genetic variation. Candida albicans, a human fungal pathogen that colonises different parts of the human body, adapts rapidly and frequently to different hostile host microenvironments. In this organism, the ability to generate large-scale genomic variation is a key adaptative mechanism triggering dangerous infections even in the presence of antifungal drugs. Understanding how fitter novel karyotypes are selected is key to determining how C. albicans and other microbial pathogens establish infections. Here, we identified the SUMO protease Ulp2 as a regulator of C. albicans genome integrity through genetic screening. Deletion of ULP2 leads to increased genome instability, enhanced genome variation and reduced fitness in the absence of additional stress. The combined stress caused by the lack of ULP2 and antifungal drug treatment leads to the selection of adaptive segmental aneuploidies that partially rescue the fitness defects of ulp2Δ/Δ cells. Short and long-read genomic sequencing demonstrates that these novel genotypes are selected via a two-step process leading to the formation of novel chromosomal fragments with breakpoints at microhomology regions and DNA repeats.
... albicans) is a major fungal pathogen that causes life-threatening infections when the host becomes debilitated or immunocompromised (3). Species of Candida, most notably C. albicans, are mostly associated with invasive, lifethreatening fungal infections in immunocompromised individuals (4). Mortality rates due to fungal infections are estimated to be as high as 45% (5), which may be due to inefficient diagnostic methods and inappropriate initial antifungal therapies (6). ...
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Candida albicans ( C. albicans ), a major fungal pathogen, causes life-threatening infections in immunocompromised individuals. Fluconazole (FLC) is recommended as first-line therapy for treatment of invasive fungal infections. Yet, the widespread use of FLC has resulted in increased antifungal resistance among different strains of Candida , especially C. albicans , which is a leading source of hospital-acquired infections. Here, by hyperspectral stimulated Raman scattering (hSRS) imaging of single fungal cells in the fingerprint window and pixel-wise spectral unmixing, we report aberrant ergosteryl ester accumulation in azole-resistant C. albicans compared to azole-susceptible species. This accumulation was a consequence of de novo lipogenesis. Lipid profiling by mass spectroscopy identified ergosterol oleate to be the major species stored in azole-resistant C. albicans . Blocking ergosterol esterification by oleate and suppressing sterol synthesis by FLC synergistically suppressed the viability of C. albicans in vitro and limited the growth of biofilm on mouse skin in vivo . Our findings highlight a metabolic marker and a new therapeutic strategy for targeting azole-resistant C. albicans by interrupting the esterified ergosterol biosynthetic pathway. Significance Statement Invasive fungal infections and increasing antifungal resistance are emerging threats to public health with high morbidity and mortality. Despite the advances in azole resistance mechanisms, it remains unclear why some fungal species are intrinsically resistant to or easily acquire resistance to multiple antifungal drugs. Here, using fingerprint SRS microscopy, we uncovered a molecular signature, aberrant ergosteryl ester accumulation, linked to the azole resistance of Candida species. An antifungal treatment strategy combining oleate (inhibitor of ersgosteryl esterification) and azole significantly attenuates the azole resistance and the viability of C. albicans in vitro and in vivo . Our work opens a new way to detect and treat azole-resistant fungal infections by targeting ergosterol metabolism.
... and Aspergillus spp., can even cause life-threatening, systemic infections [318]. Based on recent research, infections by Candida species, in hospital settings, represent an increasing health problem [319,320]. While fungi of this genus are generally benign, they can be the cause of oral candidiasis; in women, a significant percentage will suffer, sometime in their lives, from vaginal candidiasis [321,322]. ...
Article
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Flavonoids are a category of plant-derived compounds which exhibit a large number of health-related effects. One of the most well-known and studied flavonoids is kaempferol, which can be found in a wide variety of herbs and plant families. Apart from their anticarcinogenic and anti-inflammatory effects, kaempferol and its associated compounds also exhibit antibacterial, antifungal, and antiprotozoal activities. The development of drugs and treatment schemes based on these compounds is becoming increasingly important in the face of emerging resistance of numerous pathogens as well as complex molecular interactions between various drug therapies. In addition, many of the kaempferol-containing plants are used in traditional systems all over the world for centuries to treat numerous conditions. Due to its variety of sources and associated compounds, some molecular mechanisms of kaempferol antimicrobial activity are well known while others are still under analysis. This paper thoroughly documents the vegetal and food sources of kaempferol as well as the most recent and significant studies regarding its antimicrobial applications.
... It is possible that the observed shift from Candida albicans to NAC species is due to the modifications in clinical practices that have gradually selected for NAC. Over the last two decades, for instance, new antifungal drugs and new management strategies, such as use of antifungal drugs as prophylaxis and pre-emptive therapy using triazoles or echinocandins, have been recommended in high-risk hospital patient populations, in particular patients with hematological malignancies and critically ill patients [8]. Their more frequent use may have influenced the Candida spp. ...
Article
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Background Bloodstream infections caused by Candida species are responsible for significant morbidity and mortality worldwide, with an ever-changing epidemiology. We conducted this study to assess trends in the epidemiologic features, risk factors and Candida species distribution in candidemia patients in Alameda County, California. Methods We analyzed data collected from patients in Alameda County, California between 2017 and 2020 as part of the California Emerging Infections Program (CEIP). This is a laboratory-based, active surveillance program for candidemia. In our study, we included incident cases only. Results During the 4-year period from January 1st, 2017, to December 31st, 2020, 392 incident cases of candidemia were identified. The mean crude annual cumulative incidence was 5.9 cases per 100,000 inhabitants (range 5.0–6.5 cases per 100,000 population). Candida glabrata was the most common Candida species and was present as the only Candida species in 149 cases (38.0%), followed by Candida albicans, 130 (33.2%). Mixed Candida species were present in 13 patients (3.3%). Most of the cases of candidemia occurred in individuals with one or more underlying conditions. Multivariate regression models showed that age ≥ 65 years (RR 1.66, CI 1.28–2.14), prior administration of systemic antibiotic therapy, (RR 1.84, CI 1.06–3.17), cirrhosis of the liver, (RR 2.01, CI 1.51–2.68), and prior admission to the ICU (RR1.82, CI 1.36–2.43) were significant predictors of mortality. Conclusions Non-albicans Candida species currently account for the majority of candidemia cases in Alameda County.
... Marine-derived fungi receive significant attention as natural sources of drugs because of their impressive biological activities. 1 During recent decades, the pharmacology of antimycotics has advanced significantly, although common invasive fungal infections are still believed to have a high mortality rate. 2,3 Melearoride-A (1), a novel 13-membered macrolide isolated from marine-derived fungus Penicillium meleagrinum var. viridiflavum by Koyama and co-workers in 2016 has been demonstrated to show synergic effects with fluconazole against azole-resistant Candida albicans. ...
... 4 The structure of 1 was elucidated from spectroscopic data (NMR, MS, IR). PF1163B (2), another 13-membered macrolide ( Figure 1) was isolated along with PF1163A as new antifungal antibiotics from the Penicillium sp., by Sasaki and co-workers. 5,6 The structure of PF1163B has been deduced by chemical and X-ray crystallographic analyses, and was observed to be the first known inhibitor of ERG25p, a C-4 methyl oxidase. ...
Article
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A flexible stereoselective and convergent cum divergent approach to the synthesis of two 13-membered macrolides through a common skeleton present in their structure is described in two different routes, with good overall yield. The key synthetic reactions utilized include Keck allylation, Evans asymmetric methylation, Grubbs metathesis and Julia-Kocienski olefination reaction.
... Among them, Candida albicans is the most frequently isolated pathogenic species, and the fungus is responsible for more than 50% of human candidiasis. 1 Since Candida infections are one of the major causes of morbidity and mortality worldwide, they pose a serious threat to public health. 2−4 Unfortunately, the pathogenesis of Candida species is poorly understood, the rate of infections is still increasing, and growing resistance of the fungi to systemic drugs is observed. ...
... Yield: 85 mg, (82%). 1 (br s, 2B). 13 (8). ...
... Yield: 140 mg (74%). 1 (14). 34 (16). ...
Article
Infections caused by Candida species have increased significantly in the past decades and are among the leading causes of morbidity and mortality worldwide, resulting in serious public health problems. Currently, conventional antifungals are often ineffective as Candida spp. have developed growing resistance to systemic drugs. Since inorganic metallacarboranes are known to affect cellular events, new derivatives of these abiotic compounds were tested against Candida albicans. Compounds based on cobalt bis-dicarbollide [COSAN] were studied on Candida albicans strains, including a panel of 100 clinical isolates. The presented data prove that metallacarborane derivatives are effective against clinical isolates of Candida albicans, even those resistant to systemic drugs, and show synergistic potential in combination with amphotericin B, and low toxicity against human cells and Danio rerio embryos. This paper is a consequential step in the investigations of the broad spectrum and valuable future medical applications of metallacarboranes, especially in the fight against drug-resistant pathogens.