Genomic Analyses of Cladophialophora bantiana, a Major Cause of Cerebral Phaeohyphomycosis Provides Insight into Its Lifestyle, Virulence and Adaption in Host

Abstract

Cladophialophora bantiana is a dematiaceous fungus with a predilection for causing central nervous system (CNS) infection manifesting as brain abscess in both immunocompetent and immunocompromised patients. In this paper, we report comprehensive genomic analyses of C. bantiana isolated from the brain abscess of an immunocompetent man, the first reported case in Malaysia and Southeast Asia. The identity of the fungus was determined using combined morphological analysis and multilocus phylogeny. The draft genome sequence of a neurotrophic fungus, C. bantiana UM 956 was generated using Illumina sequencing technology to dissect its genetic fundamental and basic biology. The assembled 37.1 Mb genome encodes 12,155 putative coding genes, of which, 1.01% are predicted transposable elements. Its genomic features support its saprophytic lifestyle, renowned for its versatility in decomposing hemicellulose and pectin components. The C. bantiana UM 956 was also found to carry some important putative genes that engaged in pathogenicity, iron uptake and homeostasis as well as adaptation to various stresses to enable the organism to survive in hostile microenvironment. This wealth of resource will further catalyse more downstream functional studies to provide better understanding on how this fungus can be a successful and persistent pathogen in human.

Double Vision and Gait Ataxia in an Immunocompetent 9-Year-Old Girl With Intracranial Phaeohyphomycosis

“…Most patients in previous case series received high-dose amphotericin B usually in combination with a triazole or flucytosine (4). Most reported cases have involved discrete parenchymal abscesses (5), whereas our patient's disease process was unique with multifocal lesions and significant ventriculitis with fungal debris. We opted for a trial of intraventricular amphotericin B through the patient's EVD to target the mass of organisms in her fourth ventricle.…”

Cladophialophora bantiana brain abscess and concurrent pulmonary cryptococcus neoformans infection in a patient twenty years after renal transplantation

“…While the treatment for mild to moderate cryptococcal pneumonia (without meningoencephalitis) is fluconazole 400 mg once daily for 6–12 months, this would not have been appropriate for our patient. Generally, C. bantiana has been found to have high minimum inhibitory concentrations (MIC) to fluconazole [5] , [6] , [8] , [9] , [10] , therefore fluconazole is not recommended. While the optimal antifungal therapy is unclear, some physicians have used amphotericin B, flucytosine, and either voriconazole, itraconazole, or posaconazole with some success [11] .…”

An 82‐year‐old man with a right frontal lobe rim‐enhancing lesion

“…Whole-genome sequencing of C. bantiana DNA performed by Kuan et al further elucidated its unique pathogenic properties. Having a genome length of 37.1 Mb, with 12155 predicted genes encoding 8444 hypothetical proteins, C. bantiana can produce antioxidant proteins of the superoxide dismutase, catalase, or reductase families in response to thermal stress, facilitating survival in human hosts [3]. The antioxidant properties of melanin may facilitate escape from host antimicrobial immune mechanisms and growth at body temperature, and its neurotropism may be related to its ability FRONTAL LOBE RIM-ENHANCING LESION to process phenolic compounds, which are abundant in neural tissue [2].…”