Immunopathogenesis of Emerging Candida auris and Candida haemulonii Strains

Abstract

The emergence of a multidrug-resistant Candida species, C. auris and C. haemulonii, has been reported worldwide. In Thailand, information on them is limited. We collected clinical isolates from Thai patients with invasive candidiasis. Both species were compared with a laboratory C. albicans strain. In vitro antifungal susceptibility and thermotolerance, and pathogenesis in the zebrafish model of infection were investigated. Both species demonstrated high minimal inhibitory concentrations to fluconazole and amphotericin B. Only C. auris tolerated high temperatures, like C. albicans. In a zebrafish swim-bladder-inoculation model, the C. auris-infected group had the highest mortality rate and infectivity, suggesting the highest virulence. The case fatality rates of C. auris, C. haemulonii, and C. albicans were 100%, 83.33%, and 51.52%, respectively. Further immunological studies revealed that both emerging Candida species stimulated genes involved in the proinflammatory cytokine group. Interestingly, the genes relating to leukocyte recruitment were downregulated only for C. auris infections. Almost all immune response genes to C. auris had a peak response at an early infection time, which contrasted with C. haemulonii. In conclusion, both emerging species were virulent in a zebrafish model of infection and could activate the inflammatory pathway. This study serves as a stepping stone for further pathogenesis studies of these important emerging species.

Candida auris: An Overview of the Emerging Drug-Resistant Fungal Infection

“…First reported in 2009 at a hospital in Japan, an isolate from the external ear emerged as a multidrug-resistant (MDR) fungus, Candida auris [ 1 2 ]. Initially, C. auris isolates were grouped into four geographically restricted clades: clade I (South Asia), clade II (East Asia), clade III (South Africa), and clade IV (South America) [ 3 4 5 ], a possible fifth clade from Iran has also been reported [ 3 ].…”

“…Initially, C. auris isolates were grouped into four geographically restricted clades: clade I (South Asia), clade II (East Asia), clade III (South Africa), and clade IV (South America) [ 3 4 5 ], a possible fifth clade from Iran has also been reported [ 3 ]. Following this classification, approximately thirty-nine countries, which include but not limited to North America, South America, Europe, Africa, the Middle East, and East Asia have reported cases of C. auris infection [ 1 4 ]. The incidence and prevalence of this infection have increased and are observed in immunocompromised patients or those who have been hospitalized for a long time [ 4 6 ].…”

“…They are commensal colonizers of all host mucosal surfaces [ 14 ]. However, C. auris prefers to colonize the skin than other mucosal surfaces such as the gastrointestinal tract, leading to potential person-to-person transmission [ 1 3 15 ]. In addition, C. auris can spread to internal organs through systemic bloodstream infection known as candidemia and is associated with 30 – 70% crude mortality rate [ 3 16 17 ].…”

Avaliação da produção e composição de vesículas extracelulares de Candida haemulonii

“…A incidência e susceptibilidade do paciente às infecções podem ser associadas a fatores extrínsecos, por exemplo, como localização geográfica e vulnerabilidade socioeconômica; bem como por fatores intrínsecos, em especial ao estado de imunossupressão do paciente (Pfaller and Diekema 2007, Magill, Edwards et al 2014, Pharkjaksu, Boonmee et al 2021. Ressalta-se que grande parte dos casos atuais de doenças fúngicas emergentes são causadas pelos gêneros Aspergillus spp e Candida spp.…”

“…Em modelo de peixe-zebra (Danio rerio), 8 horas após a infecção, C. haemulonii apresentou aumento da carga fúngica e a maioria dos genes de expressão de citocinas próinflamatórias e inflamatórias foram regulados positivamente (Pharkjaksu, Boonmee et al 2021). Enquanto isso, pode-se sugerir pelos resultados encontrados que a levedura de C.…”