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Clinical Manifestations of Candidiasis: Beyond Candida Albicans

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Clinical Manifestations of Candidiasis: Beyond Candida Albicans Virology & Immunology Journal ISSN: 2577-4379 Clinical Manifestations of Candidiasis: Beyond Candida albicans Courtney Smith and Michael C Hanna* Review Article Department of Biology, University of Texas at San Antonio, USA Volume 3 Issue 3 Received Date: July 18, 2019 *Corresponding author: Michael C Hanna, University of Texas at San Antonio, San Published Date: August 23, 2019 Antonio, USA, Email: [email protected] DOI: 10.23880/vij-16000219 Abstract Fungal infections, including the Candida, species, are increasingly becoming problematic over the last two decades particularly in immunocompromised individuals. While there are over 150 different species only a few are pathogenic. The Candida species can evade the immune system and become pathogenic by a variety of factors including morphology, escaping phagocytosis, expression of adhesins and invasins, biofilm production due to contact sensing and thigmotropism, inhibition of the cytokine, interleukin 17, and production by the host. Candida infections produce both non-life, and life threatening manifestations and certain risk factors make infections more likely. Clinical manifestations include oral, genitourinary, gastrointestinal, and cutaneous candidiasis. Diagnosis of candidiasis can be problematic, however antigen testing, agar growth, and microscopic examination are available. Treatment of candidiasis rely on three principal antifungal agents; azoles, polyenes, and echinocandins. These three drug classes have specific drug target. Keywords: Pseudohyphae; Chlamydospores; Hyphal Cells; Albicans Abbreviations: PAMPs: Pathogen-Associated true and opportunistic pathogen is that a true pathogen is Molecular Patterns; TLRs: Toll-like Receptors; CLRs: C- an infectious agent that causes disease in any susceptible type Lectin Receptors; MR: Mannose Receptor. host. In comparison, an opportunistic pathogen is a causative agent that generally only causes disease in the Introduction immunocompromised individuals and rarely in healthy patients. Lastly, rare “emerging” opportunistic fungi are The occurrence and prevalence of invasive fungal pathogens that are not commonly seen and are generally infections have been increasing over the past few reported in severely immunocompromised patients. decades, particularly in the immunocompromised patients and or individuals with predisposing conditions Fungal species generally grow in three main [1]. The increase of fungal infections over the past two morphologies: yeast, hyphae, and pseudohyphae. decades is multifactorial, including patient demographics, However, Candida species have been noted to also higher occurrence of chronic diseases, and produce chlamydospores in vitro and rarely in infected immunocompromised individuals, etcetera [2]. tissues. Yeast cells are single cells that are spherical and can display both axial and bipolar budding patterns. Fungal pathogens can be broadly grouped into three Hyphae and pseudohyphae are also referred to as categories: opportunistic, true pathogens, and rare filamentous morphologies because the cells generally “emerging” opportunistic fungi. The difference between a grow in a polarized manner and elongate. What Clinical Manifestations of Candidiasis: Beyond Candida albicans Virol Immunol J 2 Virology & Immunology Journal differentiates these two cells types is that hyphae cells are These a and alpha stains have been shown to be capable uniform in width and have true septa lacking of mating and form a tetraploid. This alternation of the constrictions, whereas pseudohyphae are ellipsoidal and cell type from diploid to tetraploid and then return to have constrictions at the septal junctions. In both yeast diploid without meiosis is termed ‘parasexual.' Before and pseudohyphae, nuclear division occurs, and septum undergoing the parasexual cycle, diploid cells must switch ring forms entirely across the mother-daughter bud neck. to an opaque phase. Once in the opaque phase, mating is On the other hand, those events occur within the germ like Saccharomyces cerevisiae. tube during the first cell division for hyphal cells. Additionally, the initial germ tube development happens Candida albicans is one of the most researched and before the G 1/S phase transition, whereas in yeast and clinically isolated opportunistic pathogens. Non-albicans pseudohyphae, in synchrony with the cell cycle. Upon Candida species (NAC) has been on the rise of being finishing the first cell division, hyphal cells arrest in G1 reported as colonizers and causative agents [5]. Many of cell phase until enough cytoplasmic mass has these NAC infections account for approximately 50% of accumulated to move into the next cell cycle. As a result, the non-superficial Candida infections; most commonly hyphal cells have less branched compared to caused by C. glabrata, C. tropicalis, and C. parapsilosis pseudohyphae cells. All these morphologies discussed are [5,10]. vegetative cell types. The final morphological structure is the chlamydospores. These are large, round, and thick- While specific aspects of Candida species have been walled cells that customarily formed at the ends of discussed in previously published papers; they primarily hyphae filaments. Chlamydospores tend to form under focused on Candida albicans. This review focuses on stressful and poor nutrient environments. Two Candida complying with current knowledge of epidemiology and species have been cited as forming chlamydospores: C. pathogenicity, clinical manifestations and therapeutic albicans and C. dubliniensis, along with other classical strategies beyond Candida albicans that are of clinical dimorphic fungi [3,4]. This cell structure is rare, and little relevance. is known about its function. Candida Species Distribution The Candida species are members of the kingdom There are over 150 species of Candida in nature, but Fungi, the phylum Ascomycota, class Hemiascomycota, only a small portion are human pathogens. Over the past and lastly the order Saccharomycetales [5,6]. There are few decades, the incidence of C. albicans has decreased more than 150 known Candida species; however, only 15 and has begun to shift to non-albicans species. This shift of those species are of clinical importance: Candida has many factors and may be due to immunosuppression, albicans, Candida glabrata, Candida tropicalis, Candida increase the use of broad-spectrum antibiotics, and an parapsilosis, Candida krusei, Candida guilliermondii, increase in older infected patients. As the Candida Candida lusitaniae, Candida dubliniensis, Candida infections shift more to non-albicans species, the concern pellicu¬losa, Candida kefyr, Candida lipolytica, Candida increases. famata, Candida inconspicua, Candida rugosa, and Candida norvegensis [7]. Isolation frequencies vary among these In North America, C. albicans was isolated 64% in species, but it has been determined that approximately Canada and 48.9% I in the USA in during the 1990's but 95% of Candida infections are caused by C. albicans, C. has since decreased to 38% over the past two decades tropicalis, C. glabrata, C. parapsilosis, and C. krusei [7]. and shifted towards C. tropicalis, C. glabrata, and C. Candida species are either diploid or haploid. A few parapsilosis [7]. Upon looking at Candida species causing Candida species that are haploid include C. glabrata, C. invasive candidiasis, in Latin America C. albicans was lusitaniae, and C. guilliermondii [8,9]. The other Candida isolated most often followed by C. parapsilosis. However, species including C. tropicalis, C. parapsilosis, C. albicans, when compared to North America, C. glabrata was more and C. dubliniensis are all diploid [8]. However, C. albicans common than in Latin America [7]. These results are has been seen in the diploid state; this state has been assumed to be associated with poor maintenance of observed during periods of increased stress and during indwelling medical devices and infection control methods. mating. In European countries, the distribution of Candida Candida albicans natural isolates are diploid and species varies from country to country. For instance, in initially thought that it did not to have a sexual form of Finland C. albicans was found to be the most common reproduction. While conventional meiosis has not been species followed by C. glabrata; this distribution is similar observed; C. albicans has two mating types (a and alpha). to that of Sweden and Switzerland [7]. Whereas, in Spain Courtney Smith and Michael C Hanna. Clinical Manifestations of Candidiasis: Copyright© Courtney Smith and Michael C Hanna. Beyond Candida albicans. Virol Immunol J 2019, 3(3): 000219. 3 Virology & Immunology Journal C. albicans was isolated less than half followed by C. C. parapsilosis, C. tropicalis, C. dubliniensis, and C. parapsilosis being the most common non-albicans species. albicans); also only three species have been noted forming This distribution was like that of Italy. Other European the main morphologies (C. albicans, C. tropicalis, C. countries, including Germany, Denmark, and the United dublininensis) [4]. The ability to switch between various Kingdom, C. albicans was isolated the majority of times morphologies aids in adaptation and persistence in followed by C. glabrata [7]. different niches inside a host. Until recently, Candida albicans was the predominant Asteroid bodies (AB) have been described in Candida; species worldwide causing at least 80% of the reported these bodies are responsible for invasive mycosis [14]. Candida infections. Nevertheless, over
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