Candida parapsilosis infection in very low birthweight infants

Clerihew, Linda; Lamagni, Theresa; Brocklehurst, Peter; McGuire, William

doi:10.1136/fnn.2006.097758

Cited by 70 publications

(64 citation statements)

References 5 publications

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“…This is particularly important since lipid-rich total parenteral nutrition is commonly administered to low-birth-weight neonates. The use of central venous catheters to deliver parenteral nutrition solutions is a well established risk factor for invasive candida infections, although no significant difference in the frequency of central venous catheter use between infants infected with C. parapsilosis and those infected with C. albicans has been noted (6,7,27). Interestingly, medium-chain-length lipid emulsions can increase C. albicans growth rates (28), which can be linked to the production of lipases.…”

Section: Discussionmentioning

confidence: 99%

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Targeted gene deletion in Candida parapsilosis demonstrates the role of secreted lipase in virulence

Gácser¹,

Trofa²,

Schäfer³

et al. 2007

J. Clin. Invest.

131

136

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Candida parapsilosis is a major cause of human disease, yet little is known about the pathogen's virulence. We have developed an efficient gene deletion system for C. parapsilosis based on the repeated use of the dominant nourseothricin resistance marker (caSAT1) and its subsequent deletion by FLP-mediated, site-specific recombination. Using this technique, we deleted the lipase locus in the C. parapsilosis genome consisting of adjacent genes CpLIP1 and CpLIP2. Additionally we reconstructed the CpLIP2 gene, which restored lipase activity. Lipolytic activity was absent in the null mutants, whereas the WT, heterozygous, and reconstructed mutants showed similar lipase production. Biofilm formation was inhibited with lipase-negative mutants and their growth was significantly reduced in lipid-rich media. The knockout mutants were more efficiently ingested and killed by J774.16 and RAW 264.7 macrophage-like cells. Additionally, the lipase-negative mutants were significantly less virulent in infection models that involve inoculation of reconstituted human oral epithelium or murine intraperitoneal challenge. These studies represent what we believe to be the first targeted disruption of a gene in C. parapsilosis and show that C. parapsilosis-secreted lipase is involved in disease pathogenesis. This efficient system for targeted gene deletion holds great promise for rapidly enhancing our knowledge of the biology and virulence of this increasingly common invasive fungal pathogen.

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Section: Discussionmentioning

confidence: 99%

“…The fungus is particularly associated with disease in premature infants and immunocompromised adults and is a major cause of nosocomial infection in intensive care units (6,7). Despite increasing clinical importance, little is known about the genetic basis of fungal virulence traits that enable C. parapsilosis to cause disease.…”

Section: Introductionmentioning

confidence: 99%

Targeted gene deletion in Candida parapsilosis demonstrates the role of secreted lipase in virulence

Gácser¹,

Trofa²,

Schäfer³

et al. 2007

J. Clin. Invest.

131

136

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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%

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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“…are rare in this population [3,5,7]. C. albicans accounts for the majority of infections, but C. parapsilosis is emerging as a pathogen and accounts for 25% of invasive fungal infections in VLBW infants [11,12]. Other species such as C. glabrata and C. krusei which are often resistant to azoles are becoming more important in adult populations [13][14][15][16][17][18] but have not yet emerged as significant pathogens in the NICU [7,[19][20][21].…”

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confidence: 99%

Triazole Use in the Nursery: Fluconazole, Voriconazole, Posaconazole, and Ravuconazole

Watt¹,

Manzoni²,

Cohen‐Wolkowiez³

et al. 2013

Current Drug Metabolism

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Invasive fungal infections in infants admitted to the neonatal intensive care unit are common and often fatal. The mainstay of therapy against invasive fungal infections is antifungal agents. Over the last two decades, the development and approval of these drugs evolved tremendously, and the azole class emerged as important agents in the treatment and prevention of invasive fungal infections. Among the azoles, fluconazole has been used extensively due to its favorable pharmacokinetics, excellent activity against Candida spp, and safety profile. This drug has been well studied in children but data for its use in infants are largely limited to Candida prophylaxis studies. Voriconazole, a second generation triazole, has excellent activity against Candida and Aspergillus spp. However, data on its use in neonates are extremely limited. Posaconazole and Ravuconazole are the newest agents of the triazole family. The antimicrobial spectrum of posaconazole is similar to voriconazole, but with additional activity against zygomycetes. Experience with posaconazole in children is very limited, and there are no reports of its use in infants. Ravuconazole is not approved for use by the FDA but studies in animals and humans show that it is often fungicidal and has favorable pharmacokinetics. In conclusion, the management of invasive fungal infections has progressed greatly over the last two decades with the azole antifungals playing a significant role. Related to this class, future research is needed in order to better assess dosing, safety, schedules and areas of use of these agents in infants admitted to the neonatal intensive care unit.

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Candida parapsilosis infection in very low birthweight infants

Cited by 70 publications

References 5 publications

Targeted gene deletion in Candida parapsilosis demonstrates the role of secreted lipase in virulence

Targeted gene deletion in Candida parapsilosis demonstrates the role of secreted lipase in virulence

Candida parapsilosis Secreted Lipase as an Important Virulence Factor

Triazole Use in the Nursery: Fluconazole, Voriconazole, Posaconazole, and Ravuconazole

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