<i>Candida parapsilosis</i>and the neonate: epidemiology, virulence and host defense in a unique patient setting

Chow, Brian; Linden, Jennifer R.; Bliss, Joseph M.

doi:10.1586/eri.12.74

Cited by 43 publications

(42 citation statements)

References 110 publications

(128 reference statements)

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“…To expand our knowledge about the role of fungal eicosanoids in pathogenesis, we examined lipid mediator production in another important human fungal pathogen, C. parapsilosis . As the incidence of this species has increased over the past two decades and the patient group at risk includes immunosuppressed children and adults as well as neonates, understanding the pathogenesis of C. parapsilosis has gained increased attention [16,28]. Preliminary studies have started to elucidate the prostaglandin profile of this species [17], however, the involved biosynthetic pathways and the presence or role of other fungal eicosanoids remained elusive.…”

Section: Discussionmentioning

confidence: 99%

Eicosanoid biosynthesis influences the virulence of Candida parapsilosis

et al. 2018

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Lipid mediators, derived from arachidonic acid metabolism, play an important role in immune regulation. The functions of bioactive eicosanoids range from modulating cytokine signaling and inflammasome formation to anti-inflammatory and pro-resolving activities. Human pathogenic fungi such as Candida albicans, Candida parapsilosis, Cryptococcus neoformans and Aspergillus fumigatus have been shown to produce such lipid mediators, associated with their virulence. To date, investigations into the molecular mechanisms of fungal eicosanoid biosynthesis in different species have revealed that several genes are associated with prostaglandin production. However, these routes remain uncharacterized in C. parapsilosis with early results suggesting it uses pathways distinct from those found in C. albicans. Therefore, we aimed to identify and characterize C. parapsilosis genes involved in eicosanoid biosynthesis. Following arachidonic acid treatment of C. parapsilosis cells, we identified several genes interfering with prostaglandin production. Out of the identified genes, homologues of a multi copper oxidase (FET3), an Acyl-CoA thiolase (POT1) and an Acyl-CoA oxidase (POX1-3) were found to play a significant role in prostaglandin synthesis. Furthermore, all three genes were confirmed to enhance C. parapsilosis pathogenicity, as the corresponding deletion mutants were cleared more efficiently by human macrophages and induced higher levels of pro-inflammatory cytokines. In addition, the mutants were less virulent than the wild-type strain in a mouse model of systemic infection. Taken together, we identified three genes that regulate eicosanoid biosynthesis in C. parapsilosis and impact the fungus’ virulence.

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Section: Discussionmentioning

confidence: 99%

Eicosanoid biosynthesis influences the virulence of Candida parapsilosis

et al. 2018

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“…Several recent studies have further reported C. parapsilosis to be the predominant species causing neonatal infections at intensive care units (ICU), threatening especially low birth weight infants, with significant neonatal mortality [7,[22][23][24]. Additionally, diverse adult patients with diminished immunity are also at risk [25][26][27][28].…”

Section: Introductionmentioning

confidence: 99%

“…A number of reports and previous reviews have already demonstrated the role of C. parapsilosis in nosocomial infections [23,24,29,36]. In this review, we aim to provide a description of a critically important effector protein of C. parapsilosis that has been proven to promote invasion, including altering host immune responses to the benefit of the fungus.…”

Section: Introductionmentioning

confidence: 99%

Candida parapsilosis Secreted Lipase as an Important Virulence Factor

Tóth

Vágvölgyi

et al. 2017

CPPS

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Abstract:The prevalence of Candida parapsilosis, an opportunistic human pathogenic fungal species, is increasing at an alarming rate in the hospital environment. Patients at risk for C. parapsilosis infection include those with immunosuppression, such as individuals with cancer, AIDS, and low birth weight premature neonates as well as patients that had undergone abdominal surgery. Neonatal candidiasis caused by C. parapsilosis has been widely reported across the globe. Various reports have shown that, compared to other Candida species, certain C. parapsilosis clinical isolates were less susceptible to antifungals such as amphotericin B, fluconazole, and caspofungin. In addition, some studies have even reported multi-echinocandin or multi-azole resistant strains of C. parapsilosis. C. parapsilosis has several virulence factors that contribute to its capacity for host invasion and among these factors extracellular lipases have a major role in pathogenesis. In this review we have collected all the recent relevant studies that confirm the involvement of secreted lipases in C. parapsilosis pathogenesis, using both in vitro and in vivo models of infection. Of particular note, an available lipase deficient C. parapsilosis strain has been utilized to demonstrate that the lack of secreted lipases decreased virulence, reduced tissue damage, and was less able to survive within phagocytes or mice compared to the wild type. Since fungal secreted lipases have different characteristics than lipolytic enzymes present in humans, C. parapsilosis extracellular lipases may be potential targets for the development of novel antifungal drugs.

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“…Historically, Candida albicans was the most frequent cause of these infections, accounting for 70 to 80% of isolates from infected patients (5). However, infections caused by non-albicans Candida species, including C. glabrata and C. parapsilosis, are increasing in frequency worldwide (6)(7)(8). In some centers, C. parapsilosis has emerged as the leading cause of invasive candidiasis, particularly in newborns (9,10).…”

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confidence: 99%