Echinocandins As Biotechnological Tools for Treating Candida Auris Infections
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Journal of Fungi Review Echinocandins as Biotechnological Tools for Treating Candida auris Infections 1,2, 1, 1,2 Elizabete de Souza Cândido y , Flávia Affonseca y, Marlon Henrique Cardoso and Octavio Luiz Franco 1,2,* 1 S-Inova Biotech, Programa de Pós Graduação em Biotecnologia, Universidade Católica Dom Bosco, Campo Grande 79117900; Brazil; [email protected] (E.d.S.C.); flavia.aff[email protected] (F.A.); [email protected] (M.H.C.) 2 Centro de Análises Proteômicas e Bioquímicas, Universidade Católica de Brasília, Brasília 70790160, Brazil * Correspondence: [email protected] These authors equally contributed for this work. y Received: 31 July 2020; Accepted: 9 September 2020; Published: 22 September 2020 Abstract: Candida auris has been reported in the past few years as an invasive fungal pathogen of high interest. Its recent emergence in healthcare-associated infections triggered the efforts of researchers worldwide, seeking additional alternatives to the use of traditional antifungals such as azoles. Lipopeptides, specially the echinocandins, have been reported as an effective approach to control pathogenic fungi. However, despite its efficiency against C. auris, some isolates presented echinocandin resistance. Thus, therapies focused on echinocandins’ synergism with other antifungal drugs were widely explored, representing a novel possibility for the treatment of C. auris infections. Keywords: lipopeptides; echinocandins; Candida auris; infections; antifungal drugs 1. Introduction Candidiasis is one of the most common causes of fungal infection on a global scale and includes both superficial and invasive infections. The major concern is associated with patients in intensive care units (ICU) with high mortality rates. There are several fungal species isolated in the clinical setting responsible for these infections. Candida albicans is the most studied and frequently isolated species from nosocomial infections, but recently a new species, named Candida auris, has raised great concern regarding disorders caused by fungi [1,2]. 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. This new species appears as a major concern for health systems, since several isolates have already been confirmed as resistant to three antifungals drugs classes [5,6]. C. auris was reported for the first time in 2009. The strains were isolated from the external auditory canal of a Japanese patient. This fungus was discovered through the sequencing of the ribosomal DNA D1/D2 domain and nuclear ITS region. It was reported that C. auris is phylogenetically close to Candida ruelliae and Candida haemulonii [7]. In the same year (2009), 15 patients with chronic otitis media presented Candida species very closely related to C. haemulonii in South Korean hospitals [8]. Over the years, numerous other countries have isolated C. auris strains (Figure1), including Kuwait [9,10], South Africa [11], Venezuela [12], Spain [13], Oman [14], Israel [15], Colombia [16], Panama [17], Pakistan [5], the United Kingdom [18], Australia [19] and Saudi Arabia [20], among others. J. 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This SouthSouthThis classification AmericanAmerican >> wasSouthSouth carried AsianAsian out >> (South(South using wholeAfrican African genome == EastEast sequenceAsian)Asian) [4,21].[4,21]. data from global clinical data. Each of classification was carried out using whole genome sequence data from global clinical data. Each of these clades differs phenotypically. Moreover, in terms of virulence, these isolates follow the order: these clades differs phenotypically. Moreover, in terms of virulence, these isolates follow the order: SouthSouth American American> South > South Asian Asian> >(South (South AfricanAfrican == EastEast Asian) Asian) [4,21]. [4,21 ]. FigureFigureFigureFigure 1.1. 1. GlobalGlobalGlobal 1. Global distributiondistribution distribution distribution ofof of CandidaCandidaofCandida Candida aurisauris auris auris between betweenbetween between 2009 2009 andandand 2019. 2019. 2019.2019. 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