Candidiasis

Vázquez, José Antonio; Sobel, Jack D.

doi:10.1007/978-1-4419-6640-7_11

Cited by 25 publications

(21 citation statements)

References 350 publications

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“…Over 165 species of Candida exist in nature; only a few species, however, are recognized causes of disease in humans (Table 1) [Vazquez and Sobel, 2011;Pfaller and Diekema, 2007;Pappas et al 2003]. C. albicans and C. glabrata account for approximately 7080% of Candida spp.…”

Section: Epidemiologymentioning

confidence: 99%

“…Disseminated candidiasis is frequently associated with multiple deep organ infections or may involve single organ infection (Table 2). Diagnosis Unfortunately, findings from laboratory studies are either negative or nonspecific [Vazquez and Sobel, 2011;Pappas, 2006]. Clinicians are required to act definitively and early based on a high index of suspicion.…”

Section: Clinical Manifestationmentioning

confidence: 99%

“…The treatment of Candida infections varies substantially and is based on the anatomic location of the infection, the patients' underlying disease and immune status, the patients' risk factors for infection, the specific species of Candida responsible for infection, and in some cases, the susceptibility of the strain to the different antifungal drugs [Vazquez and Sobel, 2011;Pappas et al 2009 [Miceli and Chandrasekar, 2012]. The antifungal spectrum of activity, common drugdrug interactions, and side effects are shown in Table 4.…”

Section: Managementmentioning

confidence: 99%

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Invasive fungal infections in transplant recipients

Vázquez

Miceli

Alangaden

2013

Therapeutic Advances in Infection

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Invasive fungal infections are an important cause of morbidity and mortality in hematopoietic stem cell transplant and solid organ transplant recipients. Evolving transplant modalities and techniques, complex and extensive immunosuppressant strategies, and the increased use of broad spectrum antifungal prophylaxis has greatly impacted the epidemiology and temporal pattern of invasive fungal infections in the transplant population. The goal of this article is to provide an up-to-date review of the most commonly encountered invasive fungal infections seen in transplant recipients, including epidemiology, risk factors, clinical features, diagnostic dilemmas, management and their overall influence on outcomes.

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Section: Epidemiologymentioning

confidence: 99%

Section: Clinical Manifestationmentioning

confidence: 99%

Section: Managementmentioning

confidence: 99%

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Invasive fungal infections in transplant recipients

Vázquez

Miceli

Alangaden

2013

Therapeutic Advances in Infection

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“…In immunocompetent individuals, C. albicans causes superficial mucosal diseases such as thrush in infants and vulvovaginitis in women. Immunocompromised individuals develop either more severe mucosal disease, as is the case with people living with HIV/AIDS, or invasive infections of the bloodstream and deep organs (2). One major risk factor for the latter manifestation of C. albicans infection is neutropenia, or decreased numbers of circulating neutrophils (2).…”

mentioning

confidence: 99%

Candida albicans Triggers NLRP3-Mediated Pyroptosis in Macrophages

et al. 2014

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Pyroptosis is an inflammasome-mediated programmed cell death pathway triggered in macrophages by a variety of stimuli, including intracellular bacterial pathogens. Activation of pyroptosis leads to the secretion of interleukin-1␤ (IL-1␤) and pore-mediated cell lysis. Although not considered an intracellular pathogen, Candida albicans is able to kill and, thereby, escape from macrophages. Here, we show that C. albicans-infected bone marrow-derived macrophages (BMDM) and murine J774 macrophages undergo pyroptotic cell death that is suppressed by glycine and pharmacologic inhibition of caspase-1. Infection of BMDM harvested from mice lacking components of the inflammasome revealed that pyroptosis was dependent on caspase-1, ASC, and NLRP3 and independent of NLRC4. In contrast to its role during intracellular bacterial infection, pyroptosis does not restrict C. albicans replication. Nonfilamentous Candida spp. did not trigger pyroptosis, while Candida krusei, which forms pseudohyphae in macrophages, triggered much lower levels than did C. albicans. Interestingly, a Saccharomyces cerevisiae strain from the filamentous background ⌺1278 also triggered low, but significant, levels of pyroptosis. We have found that deletion of the transcription factor UPC2 decreases pyroptosis but has little effect on filamentation in the macrophage. In addition, a gainof-function mutant of UPC2 induces higher levels of pyroptosis than does a matched control strain. Taken together, these data are most consistent with a model in which filamentation is necessary but not sufficient to trigger NLRP3 inflammasome-mediated pyroptosis. This is the first example of a fungal pathogen triggering pyroptosis and indicates that C. albicans-mediated macrophage damage is not solely due to hypha-induced physical disruption of cellular integrity.

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“…andida albicans is one of the most important human fungal pathogens and causes disease in both immunocompetent and immunocompromised people (1,2). Mucocutaneous diseases, such as vulvovaginitis and diaper dermatitis, affect those with intact immune systems.…”

mentioning

confidence: 99%

Efg1 Directly RegulatesACE2Expression To Mediate Cross Talk between the cAMP/PKA and RAM Pathways during Candida albicans Morphogenesis

2014

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The cyclic AMP/protein kinase A (cAMP/PKA) and regulation of Ace2 and morphogenesis (RAM) pathways are important regulators of the yeast-to-hypha transition in Candida albicans that interact genetically during this process. To further understand this interaction, we have characterized the expression of ACE2 during morphogenesis. In normoxic, planktonic conditions, ACE2 expression is very low in stationary-phase cells at both the mRNA and protein levels. Upon shifting to Spider medium, ACE2/Ace2p levels increase. Although Ace2 is not absolutely required for hypha formation, ace2⌬/⌬ mutants show delayed hypha formation in Spider medium (but not others) and morphological changes to the hyphal tip and lateral yeast. We also show that Efg1 directly binds the promoter of Ace2 in stationary phase, and ACE2 levels are increased in strains lacking Efg1 and the protein kinase A proteins Tpk1 and Tpk2, indicating that the PKA pathway directly regulates ACE2 expression. ACE2 expression is positively regulated by Tec1 and Brg1, which bind the promoters of ACE2 in hyphal cells but not in the yeast phase. Under embedded conditions, Efg1 is dispensable for filamentation and Ace2 is required. We have found that ACE2 expression is much higher in embedded cells than in planktonic cells, providing a potential rationale for this observation. Taken together, our observations indicate that the PKA pathway directly regulates the RAM pathway under specific conditions and are consistent with a model where the two pathways carry out similar functions that depend on the specific environmental context.

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Candidiasis

Cited by 25 publications

References 350 publications

Invasive fungal infections in transplant recipients

Invasive fungal infections in transplant recipients

Candida albicans Triggers NLRP3-Mediated Pyroptosis in Macrophages

Efg1 Directly RegulatesACE2Expression To Mediate Cross Talk between the cAMP/PKA and RAM Pathways during Candida albicans Morphogenesis

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