Lipidomics Approaches: Applied to the Study of Pathogenesis in Candida Species

Background:: Candida species are in various parts of the human body as commensals. However, they can cause local mucosal infections and, sometimes, systemic infections in which Candida species can spread to all major organs and colonize them. Objective:: For the effective treatment of the mucosal infections and systemic life-threatening fungal diseases, a considerably large number of antifungal drugs have been developed and used for clinical purposes that comprise agents from four main drug classes: the polyenes, azoles, echinocandins, and antimetabolites. Method: : The synthesis of some of these drugs is available, allowing synthetic modification of the molecules to improve the biological activity against Candida species. The synthetic methodology for each compound is reviewed. Results: : The use of these compounds has caused a high-level resistance against these drugs, and therefore, new antifungal substances have been described in the last years. The organic synthesis of the known and new compounds is reported. Conclusion: : This article summarizes the chemistry of the existing agents, both the old drugs and new drugs, in the treatment of infections due to C. albicans, including the synthesis of the existing drugs.

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Isolation of Candida species from the gastrointestinal tract in malnourished children

American Journal of Clinical Nutrition ◽

10.1093/ajcn/27.4.345 ◽

1974 ◽

Vol 27 (4) ◽

pp. 345-349 ◽

Cited By ~ 31

Author(s):

Michael Gracey ◽

Delys E. Stone ◽

Suharjono ◽

Sunoto

Keyword(s):

Gastrointestinal Tract ◽

Candida Species ◽

Malnourished Children

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Candida species lens abscesses in infants with a history of neonatal Candida sepsis

Journal of American Association for Pediatric Ophthalmology and Strabismus ◽

10.1016/j.jaapos.2012.11.006 ◽

2013 ◽

Vol 17 (2) ◽

pp. 208-210 ◽

Cited By ~ 3

Author(s):

Natario L. Couser ◽

G. Baker Hubbard ◽

Lyndon B. Lee ◽

Amy K. Hutchinson ◽

Scott R. Lambert

Keyword(s):

Candida Species ◽

History Of ◽

Candida Sepsis

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146. antifungal Susceptibility Patterns of candida Parapsilosis Bloodstream Isolates in the US, 2008–2018

Open Forum Infectious Diseases ◽

10.1093/ofid/ofaa439.456 ◽

2020 ◽

Vol 7 (Supplement_1) ◽

pp. S203-S203

Author(s):

Brenda L Tesini ◽

Meghan Lyman ◽

Brendan R Jackson ◽

Anita Gellert ◽

William Schaffner ◽

...

Keyword(s):

Candida Species ◽

Regional Variation ◽

Antifungal Susceptibility ◽

Bloodstream Infections ◽

Emerging Infections ◽

In Vitro Susceptibility ◽

Fluconazole Resistance ◽

The Us ◽

Susceptibility Patterns

Abstract Background Multidrug resistant Candida is an increasing concern. C. parapsilosis in particular has decreased in vitro susceptibility to echinocandins. As a result, fluconazole had been favored for C. parapsilosis treatment. However, there is growing concern about increasing azole resistance among Candida species. We report on antifungal susceptibility patterns of C. parapsilosis in the US from 2008 through 2018. Methods Active, population-based surveillance for candidemia through the Centers for Disease Control and Prevention’s (CDC) Emerging Infections Program was conducted between 2008–2018, eventually encompassing 9 states (GA, MD,OR, TN, NY, CA, CO, MN, NM). Each incident isolate was sent to the CDC for species confirmation and antifungal susceptibility testing (AFST). Frequency of resistance was calculated and stratified by year and state using SAS 9.4 Results Of the 8,704 incident candidemia isolates identified, 1,471 (15%) were C. parapsilosis; the third most common species after C. albicans and C. glabrata. AFST results were available for 1,340 C. parapsilosis isolates. No resistance was detected to caspofungin (MIC50 0.25) or micafungin (MIC50 1.00) with only one (< 1%) isolate resistant to anidulafungin (MIC50 1.00). In contrast, 84 (6.3%) isolates were resistant to fluconazole and another 44 (3.3%) isolates had dose-dependent susceptibility to fluconazole (MIC50 1.00). Fluconazole resistance increased sharply from an average of 4% during 2008–2014 to a peak of 14% in 2016 with a subsequent decline to 6% in 2018 (see figure). Regional variation is also observed with fluconazole resistance ranging from 0% (CO, MN, NM) to 42% (NY) of isolates by site. Conclusion The recent marked increase in fluconazole resistance among C. parapsilosis highlights this pathogen as an emerging drug resistant pathogen of concern and the need for ongoing antifungal resistance surveillance among Candida species. Our data support the empiric use of echinocandins for C. parapsilosis bloodstream infections and underscore the need to obtain AFST prior to fluconazole treatment. Furthermore, regional variation in fluconazole resistance emphasizes the importance of understanding local Candida susceptibility patterns. Disclosures Lee Harrison, MD, GSK (Consultant)Merck (Consultant)Pfizer (Consultant)Sanofi Pasteur (Consultant)

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IMPEDIMETRIC CLAVMO PEPTIDE-BASED SENSOR DIFFERENTIATES PLOIDY OF CANDIDA SPECIES

Biochemical Engineering Journal ◽

10.1016/j.bej.2020.107918 ◽

2020 ◽

pp. 107918

Author(s):

Kalline L. Ribeiro ◽

Isaac A.M. Frías ◽

Alberto G. Silva ◽

Reginaldo G. Lima-Neto ◽

Sandra R. Sá ◽

...

Keyword(s):

Candida Species

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Review of T-2307, an Investigational Agent That Causes Collapse of Fungal Mitochondrial Membrane Potential

Journal of Fungi ◽

10.3390/jof7020130 ◽

2021 ◽

Vol 7 (2) ◽

pp. 130

Author(s):

Nathan P. Wiederhold

Keyword(s):

Membrane Potential ◽

Mitochondrial Membrane Potential ◽

Candida Species ◽

Mammalian Cells ◽

Mitochondrial Membrane ◽

Fungal Infections ◽

Published Data ◽

Candida Auris

Invasive infections caused by Candida that are resistant to clinically available antifungals are of increasing concern. Increasing rates of fluconazole resistance in non-albicans Candida species have been documented in multiple countries on several continents. This situation has been further exacerbated over the last several years by Candida auris, as isolates of this emerging pathogen that are often resistant to multiple antifungals. T-2307 is an aromatic diamidine currently in development for the treatment of invasive fungal infections. This agent has been shown to selectively cause the collapse of the mitochondrial membrane potential in yeasts when compared to mammalian cells. In vitro activity has been demonstrated against Candida species, including C. albicans, C. glabrata, and C. auris strains, which are resistant to azole and echinocandin antifungals. Activity has also been reported against Cryptococcus species, and this has translated into in vivo efficacy in experimental models of invasive candidiasis and cryptococcosis. However, little is known regarding the clinical efficacy and safety of this agent, as published data from studies involving humans are not currently available.

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