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Clinical Microbiology Reviews Mar 2019Patients with suppressed immunity are at the highest risk for hospital-acquired infections. Among these, invasive candidiasis is the most prevalent systemic fungal... (Review)
Review
Patients with suppressed immunity are at the highest risk for hospital-acquired infections. Among these, invasive candidiasis is the most prevalent systemic fungal nosocomial infection. Over recent decades, the combined prevalence of non- species outranked infections in several geographical regions worldwide, highlighting the need to understand their pathobiology in order to develop effective treatment and to prevent future outbreaks. is the second or third most frequently isolated species from patients. Besides being highly prevalent, its biology differs markedly from that of , which may be associated with ' increased incidence. Differences in virulence, regulatory and antifungal drug resistance mechanisms, and the patient groups at risk indicate that conclusions drawn from pathobiology cannot be simply extrapolated to Such species-specific characteristics may also influence their recognition and elimination by the host and the efficacy of antifungal drugs. Due to the availability of high-throughput, state-of-the-art experimental tools and molecular genetic methods adapted to , genome and transcriptome studies are now available that greatly contribute to our understanding of what makes this species a threat. In this review, we summarize 10 years of findings on pathogenesis, including the species' genetic properties, transcriptome studies, host responses, and molecular mechanisms of virulence. Antifungal susceptibility studies and clinician perspectives are discussed. We also present regional incidence reports in order to provide an updated worldwide epidemiology summary.
Topics: Antifungal Agents; Candida parapsilosis; Candidiasis; Cross Infection; Gene Expression Profiling; Humans; Incidence; Microbial Sensitivity Tests; Sequence Analysis, DNA; Sequence Analysis, RNA
PubMed: 30814115
DOI: 10.1128/CMR.00111-18 -
Journal of Fungi (Basel, Switzerland) Jan 2023Candida parapsilosis is the second most common Candida species isolated in Asia, Southern Europe, and Latin America and is often involved in invasive infections that... (Review)
Review
Candida parapsilosis is the second most common Candida species isolated in Asia, Southern Europe, and Latin America and is often involved in invasive infections that seriously impact human health. This pathogen is part of the psilosis complex, which also includes Candida orthopsilosis and Candida metapsilosis. C. parapsilosis infections are particularly prevalent among neonates with low birth weights, individuals who are immunocompromised, and patients who require prolonged use of a central venous catheter or other indwelling devices, whose surfaces C. parapsilosis exhibits an enhanced capacity to adhere to and form biofilms. Despite this well-acknowledged prevalence, the biology of C. parapsilosis has not been as extensively explored as that of Candida albicans. In this paper, we describe the molecular mechanistic pathways of virulence in C. parapsilosis and show how they differ from those of C. albicans. We also describe the mode of action of antifungal drugs used for the treatment of Candida infections, namely, polyenes, echinocandins, and azoles, as well as the resistance mechanisms developed by C. parapsilosis to overcome them. Finally, we stress the importance of the ongoing search for species-specific features that may aid the development of effective control strategies and thus reduce the burden on patients and healthcare costs.
PubMed: 36675901
DOI: 10.3390/jof9010080 -
Virulence Dec 2022Antifungal resistance to pathogens increases morbidity and mortality of immunosuppressive patients, an emerging crisis worldwide. Understanding the prevalence and... (Review)
Review
Antifungal resistance to pathogens increases morbidity and mortality of immunosuppressive patients, an emerging crisis worldwide. Understanding the prevalence and antifungal susceptibility pattern is necessary to control and treat candidiasis. We aimed to systematically analyse the susceptibility profiles of species published in the last ten years (December 2011 to December 2021) from mainland China. The studies were collected from PubMed, Google Scholar, and Science Direct search engines. Out of 89 included studies, a total of 44,716 isolates were collected, mainly comprising (49.36%), (21.89%), (13.92%), and (11.37%). The lowest susceptibility was detected for azole group; fluconazole susceptibilities against , and were 93.25%, 91.6%, 79.4%, 77.95%, 76%, 50%, and 0% respectively. Amphotericin B and anidulafungin were the most susceptible drugs for all species. Resistance to azole was mainly linked with mutations in , and genes. Mutation in and in and causing resistance to echinocandins was stated in two studies. Gaps in the studies' characteristics were detected, such as 79.77%, 47.19 %, 26.97%, 7.86%, and 4.49% studies did not mention the mortality rates, age, gender, breakpoint reference guidelines, and fungal identification method, respectively. The current study demonstrates the overall antifungal susceptibility pattern of species, gaps in surveillance studies and risk-reduction strategies that could be supportive in candidiasis therapy and for the researchers in their future studies.
Topics: Humans; Amphotericin B; Anidulafungin; Antifungal Agents; Azoles; Candida; Candida albicans; Candida glabrata; Candida parapsilosis; Candida tropicalis; Candidiasis; Echinocandins; Fluconazole; Microbial Sensitivity Tests
PubMed: 36120738
DOI: 10.1080/21505594.2022.2123325 -
The Lancet. Microbe Jun 2023Candida parapsilosis is one of the most commen causes of life-threatening candidaemia, particularly in premature neonates, individuals with cancer of the haematopoietic... (Review)
Review
Candida parapsilosis is one of the most commen causes of life-threatening candidaemia, particularly in premature neonates, individuals with cancer of the haematopoietic system, and recipients of organ transplants. Historically, drug-susceptible strains have been linked to clonal outbreaks. However, worldwide studies started since 2018 have reported severe outbreaks among adults caused by fluconazole-resistant strains. Outbreaks caused by fluconazole-resistant strains are associated with high mortality rates and can persist despite strict infection control strategies. The emergence of resistance threatens the efficacy of azoles, which is the most widely used class of antifungals and the only available oral treatment option for candidaemia. The fact that most patients infected with fluconazole-resistant strains are azole-naive underscores the high potential adaptability of fluconazole-resistant strains to diverse hosts, environmental niches, and reservoirs. Another concern is the multidrug-resistant and echinocandin-tolerant C parapsilosis isolates, which emerged in 2020. Raising awareness, establishing effective clinical interventions, and understanding the biology and pathogenesis of fluconazole-resistant C parapsilosis are urgently needed to improve treatment strategies and outcomes.
Topics: Adult; Infant, Newborn; Humans; Fluconazole; Candida parapsilosis; Microbial Sensitivity Tests; Antifungal Agents; Candidemia; Azoles
PubMed: 37121240
DOI: 10.1016/S2666-5247(23)00067-8 -
International Journal of Infectious... Mar 2021
PubMed: 33434660
DOI: 10.1016/j.ijid.2020.12.084 -
Antimicrobial Agents and Chemotherapy Jul 2022Candida parapsilosis is a common cause of invasive candidiasis worldwide and is the most commonly is7olated species among pediatric and neonatal populations. Previous...
Candida parapsilosis is a common cause of invasive candidiasis worldwide and is the most commonly is7olated species among pediatric and neonatal populations. Previous work has demonstrated that nonsynonymous mutations in the gene encoding the putative transcription factor CpMrr1 can influence fluconazole susceptibility. However, the direct contribution of these mutations and how they influence fluconazole resistance in clinical isolates are poorly understood. We identified 7 nonsynonymous mutations in 12 isolates from within a collection of 35 fluconazole-resistant clinical isolates. The mutations leading to the A854V, R479K, and I283R substitutions were further examined and found to be activating mutations leading to increased fluconazole resistance. In addition to , we identified two other genes, one encoding a major facilitator superfamily (MFS) transporter (, CPAR2_603010) and one encoding an ATP-binding cassette (ABC) transporter (, CPAR2_304370), as being upregulated in isolates carrying -activating mutations. Overexpression of in a susceptible strain and disruption in resistant clinical isolates that overexpress had little to no effect on fluconazole susceptibility. Conversely, overexpression of either or increased resistance, and disruption in clinical isolates overexpressing these genes decreased fluconazole resistance. Our findings suggest that activating mutations in represent important genetic determinants of fluconazole resistance in clinical isolates of C. parapsilosis, and unlike what is observed in Candida albicans, this is primarily driven by upregulation of both MFS (CpMdr1B) and ABC (CpCdr1B) transporters.
Topics: ATP-Binding Cassette Transporters; Antifungal Agents; Candida albicans; Candida parapsilosis; Drug Resistance, Fungal; Fluconazole; Fungal Proteins; Gene Expression Regulation, Fungal; Humans; Membrane Transport Proteins; Microbial Sensitivity Tests
PubMed: 35699442
DOI: 10.1128/aac.00289-22 -
Virulence Dec 2019Eicosanoids are bioactive lipid mediators generated in almost all mammalian cells from the oxidation of arachidonic acid and other related twenty-carbon polyunsaturated... (Review)
Review
Eicosanoids are bioactive lipid mediators generated in almost all mammalian cells from the oxidation of arachidonic acid and other related twenty-carbon polyunsaturated fatty acids (PUFA). Eicosanoids regulate various physiological functions, including cellular homoeostasis and modulation of inflammatory responses in mammals. The mode of action of these lipid mediators depend on their binding to different G-protein coupled receptors. The three main enzymatic pathways associated with their production are the COX pathway, LOX pathway and cytochrome P450 pathway. Interestingly, investigations have also revealed that several human pathogenic fungi are capable of producing these bioactive lipid mediators; however, the exact biosynthetic pathways and their function in pathogenicity are not yet extensively characterized. The aim of the current review is to summarize the recent discoveries pertaining to eicosanoid production by human pathogenic yeasts with a special focus on the opportunistic human fungal pathogen .
Topics: Arachidonic Acid; Biosynthetic Pathways; Candida parapsilosis; Eicosanoids; Genes, Fungal; Humans; Virulence; Yeasts
PubMed: 30558484
DOI: 10.1080/21505594.2018.1559674 -
Tropical Medicine and Infectious Disease Aug 2022A reliable estimate of antifungal susceptibility in candidemia patients is increasingly important to track the spread of bloodstream infections and define the true... (Review)
Review
A reliable estimate of antifungal susceptibility in candidemia patients is increasingly important to track the spread of bloodstream infections and define the true burden of the ongoing antifungal resistance. A systematic review and meta-analysis (SRMA) were conducted aiming to estimate the global prevalence and identify patterns of antifungal resistance. A systematic literature search of the PubMed, Scopus, ScienceDirect and Google Scholar electronic databases was conducted on published studies that employed antifungal susceptibility testing (AFST) on clinical isolates globally. Seventy-nine eligible studies were included. Using meta-analysis of proportions, the overall pooled prevalence of three most important antifungal drugs; Fluconazole, Amphotericin B and Voriconazole resistant were calculated as 15.2% (95% CI: 9.2-21.2), 1.3% (95% CI: 0.0-2.9) and 4.7% (95% CI: 2.2-7.3), respectively. Based on study enrolment time, country/continent and AFST method, subgroup analyses were conducted for the three studied antifungals to determine sources of heterogeneity. Timeline and regional differences in prevalence of antifungal resistance were identified with the same patterns among the three antifungal drugs. These findings highlight the need to conduct further studies to assess and monitor the growing burden of antifungal resistance, to revise treatment guidelines and to implement regional surveillance to prevent further increase in drug resistance emerging recently.
PubMed: 36006280
DOI: 10.3390/tropicalmed7080188 -
Microbiological Research Jan 2020The ability of yeast to adhere to biotic and abiotic surfaces represents an essential trait during the early stages of infection. Agglutinin-like sequence (Als)...
The ability of yeast to adhere to biotic and abiotic surfaces represents an essential trait during the early stages of infection. Agglutinin-like sequence (Als) cell-wall proteins play a key role in adhesion of Candida species. Candida parapsilosis genome encompasses 5 ALS members, of which only the role of CPAR2_404800 has been elucidated. The present project was aimed at investigating the contribution of C. parapsilosis Als proteins by generating edited strains lacking functional Als proteins. CPAR2_404770 and CPAR2_404780, further indicated as CpALS4770 and CpALS4780, were selected for the generation of single and double edited strains using an episomal CRISPR/Cas9 technology. Phenotypic characterization of mutant strains revealed that editing of both genes had no impact on the in vitro growth of C. parapsilosis or on morphogenesis. Notably, CpALS4770-edited strain showed a reduction of biofilm formation and adhesive properties to human buccal cells (HBECs). Conversely, single CpALS4780-edited strain did not show any difference compared to the wild-type strain in all the assays performed, while the double CpALS4770-CpALS4780 mutant revealed an increased ability to produce biofilm, a hyper-adhesive phenotype to HBECs, and a marked tendency to form cellular aggregates. Murine vaginal infection experiments indicated a significant reduction in CFUs recovered from BALC/c mice infected with single and double edited strains, compared to those infected with the wild-type strain. These finding clearly indicate that CpAls4770 plays a role in adhesion to biotic and abiotic surfaces, while both CpALS4770 and CpALS4780 genes are required for C. parapsilosis ability to colonize and persist in the vaginal mucosa.
Topics: Animals; Biofilms; CRISPR-Associated Protein 9; CRISPR-Cas Systems; Candida parapsilosis; Candidiasis; Cell Adhesion; Cell Culture Techniques; Female; Fungal Proteins; Gene Silencing; Genes, Fungal; Humans; Mice; Mucous Membrane; Virulence
PubMed: 31707298
DOI: 10.1016/j.micres.2019.126351 -
Journal of Fungi (Basel, Switzerland) Jul 2023Fungal diseases cause millions of deaths per year worldwide. Antifungal resistance has become a matter of great concern in public health. In recent years rates of non-... (Review)
Review
Fungal diseases cause millions of deaths per year worldwide. Antifungal resistance has become a matter of great concern in public health. In recent years rates of non- species have risen dramatically. is now reported to be the second most frequent species causing candidemia in several countries in Europe, Latin America, South Africa and Asia. Rates of acquired azole resistance are reaching a worrisome threshold from multiple reports as in vitro susceptibility testing is now starting also to explore tolerance and heteroresistance to antifungal compounds. With this review, the authors seek to evaluate known antifungal resistance mechanisms and their worldwide distribution in species infections with a specific focus on .
PubMed: 37623569
DOI: 10.3390/jof9080798