Impact of Candida auris Infection in a Neutropenic Murine Model

Abstract

Candida auris has become a global public health threat due to its multidrug resistance and persistence. Currently, there are limited murine models to study C. auris infection. Those models use a combination of cyclophosphamide and cortisone acetate, suppressing both innate and adaptive immunity. Here, we compare C. auris infection in two neutrophil-depleted murine models in which innate immunity is targeted using the monoclonal antibodies 1A8 and RB6-8C5.

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

“…Large, multifocal lesions in the myocardium without the involvement of the endocardium suggest hematogenous seeding; on day 1 abundant single and budding yeast cells were seen in the coronary arteriolae in mice infected with all C. auris lineages (Figure 4(C)). Our results are in accordance with others who observed high fungal burdens (≥×10 5 CFU/g) in the myocardium with BALB/c, A/J, neutrophil elastase-deficient and C57BL/6 neutropenic and non-neutropenic mice infected with C. auris isolates from the South American and South Asian clades [15,17]. In contrast, with the more virulent C. albicans endocardial involvement was found and myocardial involvement was primarily subendocardial, suggesting a penetration of the heart muscle by yeasts starting from the endocardium.…”

“…Similar high virulence was reported by Xin et al in A/J (100% lethality) but not in BALB/c neutropenic mice (40% lethality) using a single South American isolate [17]. Our lethality results with the South Asian clade (50-100% lethality) correlate well to those previously reported for neutropenic BALB/c or CD-1 mice (40-100% lethality) with the same or higher (from 10 7 to 10 8 CFU/mouse) infectious doses [15,16]. The lack of similar studies with the South African clade precludes comparison to our results.…”

“…Although in this study we did not examine the fungal burdens in the brain and lungs, based on the high fungal burdens in the hearts and kidneys, central nervous system and lung invasion is also feasible. However, we did not observe signs of meningeal involvement [15].…”

“…Data about in vivo virulence of different C. auris clades in mammalian hosts is scant, the available studies focus mainly on the South Asian clade [12][13][14][15][16][17], moreover, the South African clade has never been examined. Fakhim et al infected ICR outbred immunocompetent mice with inocula of 10 5 -, 10 6 and 10 7 CFU/mouse using two C. auris (both from the South Asian clade) and one C. albicans strains.…”

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.…”