Black Yeasts and Their Filamentous Relatives: Principles of Pathogenesis and Host Defense

Abstract

SUMMARY Among the melanized fungi, the so-called “black yeasts” and their filamentous relatives are particularly significant as agents of severe phaeohyphomycosis, chromoblastomycosis, and mycetoma in humans and animals. The pathogenicity and virulence of these fungi may differ significantly between closely related species. The factors which probably are of significance for pathogenicity include the presence of melanin and carotene, formation of thick cell walls and meristematic growth, presence of yeast-like phases, thermo- and perhaps also osmotolerance, adhesion, hydrophobicity, assimilation of aromatic hydrocarbons, and production of siderophores. Host defense has been shown to rely mainly on the ingestion and elimination of fungal cells by cells of the innate immune system, especially neutrophils and macrophages. However, there is increasing evidence supporting a role of T-cell-mediated immune responses, with increased interleukin-10 (IL-10) and low levels of gamma interferon (IFN-γ) being deleterious during the infection. There are no standardized therapies for treatment. It is therefore important to obtain in vitro susceptibilities of individual patients' fungal isolates in order to provide useful information for selection of appropriate treatment protocols. This article discusses the pathogenesis and host defense factors for these fungi and their severity, chronicity, and subsequent impact on treatment and prevention of diseases in human or animal hosts.

Chromoblastomycosis

“…2). The cytochrome P450 cluster involved in melanin synthesis and hydrocarbon degradation might play an important role in the virulence of the Chaetothyriales, which probably differs from the other virulence factors of fungi reported previously, such as Lac and HmgA (58), and other virulence factors (59)(60)(61)(62)(63)(64)(65). Likewise, the ACT1, BT2, and Cdc42 genes are effectively involved in cell cycle stages and the formation of the actin cytoskeleton (35), which has been related to morphogenetic switching to muriform cells, which are considered the invasive phase of agents of CBM (66) and which are also used for species distinction (35,57).…”

“…It is directly associated with an intense granulomatous response as well as with the evasion of immune mechanisms signaling the onset of disease chronicity. The time of conversion from conidia to muriform cells in in vitro studies was estimated to be 6 days (58,170).…”

Cladophialophora bantiana as an Emerging Pathogen in Animals: Case Report of Equine Endometritis and Review of the Literature

“…Of these, C. bantiana is a well-known causative agent of cerebral phaeohyphomycosis, which is often a fatal condition (8,10). Many such cases have been diagnosed in people without apparent immune deficiency (8), although there may be underlying genetic susceptibilities associated, for instance, with mutations in the CARD9 gene with subsequent decreased cytokine production by innate immune cells (7). The prognosis of cerebral phaeohyphomycosis is poor, regardless of aggressive surgical and medical treatment (8).…”

“…Mammals and birds are usually well protected from infections caused by black fungi due to their skin or feather coverage (7). Ten different Cladophialophora species are known to cause infections in humans.…”

“…bantiana is a member of the order Chaetothyriales, which are often referred to as "black yeast-like fungi" due to the ability of some representatives to produce budding cells as well as dark hyphae, depending on the life cycle and environmental conditions (7). From a clinical perspective, three groups can be distinguished within the order: (i) pathogens, which have the advantage of using vertebrate vectors and which need specialized methods to be isolated from the environment; (ii) agents of chromoblastomycosis, which have a distinct pathogenic phase in mammalian tissue; and (iii) saprobes, which cause infections only by coincidence (7). The melanized fungi are unique in being capable of causing a plethora of diseases in mammals, such as phaeohyphomycosis, eumycetoma, and chromoblastomycosis (8).…”