Comparison of in vivo pathogenicity of four Candida auris clades in a neutropenic bloodstream infection murine model

Abstract

Candida auris is an emerging worldwide concern, but comparative data about the virulence of different C. auris lineages in mammalian hosts is lacking. Different isolates of the four prevalent C. auris clades (South Asian n = 5, East Asian n = 4, South African n = 5, and South American n = 5) were compared to assess their virulence in a neutropenic murine bloodstream infection model with C. albicans as reference. C. auris, regardless of clade, proved to be less virulent than C. albicans. Highest overall mortality at day 21 was observed for the South American clade (96%), followed by the South Asian (80%), South African (45%) and East Asian (44%) clades. Fungal burden results showed close correlation with lethality. Histopathological examination revealed large aggregates of blastoconidia and budding yeast cells in the hearts, kidneys and livers but not in the spleens. The myocardium of apparently healthy sacrificed mice as well as of mice found moribund showed contraction band necrosis in case of all lineages. Regardless of clade, the heart and kidneys were the most heavily affected organs. Isolates of the same clade showed differences in virulence in mice, but a markedly higher virulence of the South American clade was clearly demonstrated.

Comparative Evaluations of the Pathogenesis of Candida auris Phenotypes and Candida albicans Using Clinically Relevant Murine Models of Infections

“…In another study, C. auris aggregative isolates were found to be less pathogenic than the nonaggregative isolates ( 17 ). So far, a limited number of animal studies have been performed to evaluate C. auris , with the majority using the intravenous systemic model ( 39 – 41 ), the most recent of which found C. auris to be less virulent than C. albicans ( 39 ). Therefore, our study was designed to comparatively evaluate the C. auris phenotypes and C. albicans using three other clinically relevant murine models of infection.…”

In vitro and in vivo interaction of caspofungin with isavuconazole against Candida auris planktonic cells and biofilms

“…The animals were rendered neutropenic by intraperitoneal injection of cyclophosphamide (Endoxan, Baxter, Deerfield, IL, United States) 4 days (150 mg/kg body weight) and 1 day (100 mg/kg body weight) before infection and then 2 and 4 days postinfection (100 mg/kg body weight) [25]. Mice were infected intravenously through the lateral tail vein with 1-1.3 × 10 7 colony-forming units (CFU) in 200 μ L physiological saline [25]. The inoculum density was confirmed by plating serial dilutions on Sabouraud dextrose agar.…”

Echinocandins as Biotechnological Tools for Treating Candida auris Infections

“…C. auris is a multidrug-resistant pathogen that has been identified in 39 countries and has spread across five continents, with a mortality rate of ~78% [ 3 ]. Furthermore, risk factors that aggravate C. auris infections include conditions such as diabetes mellitus, cardiovascular surgical interventions and gastrointestinal pathologies, hematological malignancies and even corticosteroid therapy [ 4 ]. In addition, this pathogen spreads easily in hospital environments, but its correct identification is usually challenging.…”

“…Each of these clades differs phenotypically. Moreover, in terms of virulence, these isolates follow the order: South American > South Asian > (South African = East Asian) [ 4 , 21 ].…”

“…Each of these clades differs phenotypically. Moreover, in terms of virulence, these isolates follow the order: South American > South Asian > (South African = East Asian) [4,21]. The timeline presents the first report in each country highlighted over the years, with 2009 being the year in which the first case was reported.…”