Abstract:Episodes of fungemia increased significantly over 11 years as compared with a moderate increase in positive fungal cultures and were associated with high all-cause mortality rates. More sensitive assays for early identification of fungal bloodstream infections are warranted.
“…Using a intraperitoneal murine infection model, it has been demonstrated that Cp ΔΔlip1-ΔΔlip2 cells were able to accumulate less in the kidney, liver and spleen of BALB/c mices 2 days post infection [34], but these mutant cells were eradicated within 4 days after the infection, which was significantly faster than clearance of wild type yeast [34]. As C. parapsilosis is one of the leading species associated with neonatal invasive infections, efforts have been applied to developing a suitable model to mimic newborn-related candidiasis [67][68][69]. Using newborn Sprague-Dawley rats, Trofa et al demonstrated that premature neonates were highly susceptible to candidal infections.…”
Section: In Vivo Infection Models To Study C Parapsilosis Lipase Funmentioning
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.
“…Using a intraperitoneal murine infection model, it has been demonstrated that Cp ΔΔlip1-ΔΔlip2 cells were able to accumulate less in the kidney, liver and spleen of BALB/c mices 2 days post infection [34], but these mutant cells were eradicated within 4 days after the infection, which was significantly faster than clearance of wild type yeast [34]. As C. parapsilosis is one of the leading species associated with neonatal invasive infections, efforts have been applied to developing a suitable model to mimic newborn-related candidiasis [67][68][69]. Using newborn Sprague-Dawley rats, Trofa et al demonstrated that premature neonates were highly susceptible to candidal infections.…”
Section: In Vivo Infection Models To Study C Parapsilosis Lipase Funmentioning
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.
“…Although the yeast form can bind to gut mucosal membranes with further colonization (20,49), it is thought that the filamentous morphology provides some advantage during interaction with the mammalian immune system as a part of fungal anti-host defense, and the ability of C. albicans to rapidly and reversibly switch between yeast and filamentous morphologies is crucial to its pathogenicity (16,55,65,82). In recent years, Candida infections ranked as the fourth most common cause of bloodstream infections and are the leading cause of life-threatening nosocomial fungal infections (1,87). The risk of developing opportunistic bloodstream infections is greatly increased in patients who are severely immunocompromised.…”
Candida albicans is a common opportunistic fungal pathogen and is the leading cause of invasive fungal diseases in immunocompromised individuals. The induction of cell-mediated immunity to C. albicans is one of the main tasks of cells of the innate immune system, and in vitro evidence suggests that integrin ␣ M  2 (CR3, Mac-1, and CD11b/CD18) is the principal leukocyte receptor involved in recognition of the fungus. Using ␣ M  2 -KO mice and mutated strains of C. albicans in two models of murine candidiasis, we demonstrate that neutrophils derived from mice deficient in ␣ M  2 have a reduced ability to kill C. albicans and that the deficient mice themselves exhibit increased susceptibility to fungal infection. Disruption of the PRA1 gene of C. albicans, the primary ligand for ␣ M  2 , protects the fungus against leukocyte killing in vitro and in vivo, impedes the innate immune response to the infection, and increases fungal virulence and organ invasion in vivo. Thus, recognition of pH-regulated antigen 1 protein (Pra1p) by ␣ M  2 plays a pivotal role in determining fungal virulence and host response and protection against C. albicans infection.
“…Fungal isolates are obtained in as many as 5% of all bacteremia and fungemia cases, and most of fungal isolates are Candida spp. (1,8). Furthermore, episodes of fungemia have increased significantly over the years (1).…”
Section: Discussionmentioning
confidence: 99%
“…(1,8). Furthermore, episodes of fungemia have increased significantly over the years (1). Universal amplification of fungal isolates is different from that of bacteria, so one more PCR amplification is necessary to detect fungi isolated by the chip.…”
Oligonucleotide chips targeting the bacterial internal transcribed spacer region (ITS) of the 16S-23S rRNA gene, which contains genus-and species-specific regions, were developed and evaluated. Forty-three sequences were designed consisting of 1 universal, 3 Gram stain-specific, 9 genus-specific, and 30 species-specific probes. The specificity of the probes was confirmed using bacterial type strains including 54 of 52 species belonging to 18 genera. The performance of the probes was evaluated using 825 consecutive samples that were positive by blood culture in broth medium. Among the 825 clinical specimens, 708 (85.8%) were identified correctly by the oligonucleotide chip. Most (536 isolates, or 75.7%) were identified as staphylococci, Escherichia coli, or Klebsiella pneumoniae. Thirty-seven isolates (4.5%) did not bind to the corresponding specific probes. Most of these also were staphylococci, E. coli, or K. pneumoniae and accounted for 6.3% of total number of the species. Sixty-two specimens (7.5%) did not bind the genus-or species-specific probes because of lack of corresponding specific probes. Among them, Acinetobacter baumannii was the single most frequent isolate (26/62). The oligonucleotide chip was highly specific and sensitive in detecting the causative agents of bacteremia directly from positive blood cultures.
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