Browsing by Author "Ngwenya, Mathula Lancelot"

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    Genome data mining, identification, annotation and phylogenetic analysis of P450s in pathogenic fungus Conidiobolus coronatus
    (University of Zululand, 2018) Ngwenya, Mathula Lancelot
    Conidiobolus coronatus, an entomopathogenic fungus, has the ability to infect humans and other animals (human, horse, sheep and dog), apart from insects. C. coronatus causes conidiobolomycosis in humans, which is considered a rare and neglected disease. Conidiobolomycosis is a disease of the nasal submucosa and paranasal sinuses, which slowly spreads to the nasal skin, glabella, cheek, upper lip and pharynx. Infection of the nasal and paranasal mucocutaneous tissue is known as rhinoentomophthoramycosis. None of the currently available treatments was found to be efficient in treating this fungal infection, including treatment with azole drugs, which target cytochrome P450 monooxygenases (CYPs/P450s). P450s are heme-thiolate proteins and well-known drug targets against microbial pathogens. Despite the great importance of P450s, no information on C. coronatus P450s is available. Here, for the first time, we present comprehensive in silico analysis of C. coronatus P450s. Genome wide data-mining and annotation of P450s in C. coronatus revealed the presence of 142 P450s in its genome, the highest number of P450s compared to other entomopathogenic fungi. P450 annotation revealed the presence of a large number of new P450s in C. coronatus. All 142 P450s were grouped into 12 P450 families and 21 P450 subfamilies. Except for CYP51, the most conserved P450 in fungi and well-known target of azole drugs, the other 11 P450 families are new. The new P450 families identified in C. coronatus include CYP5854-CYP5864. It is interesting that apart from CYP51, C. coronatus did not share any more P450s with other entomopathogenic fungi. Analysis of family and subfamily dynamics in C. coronatus revealed that among 12 P450 families, only five P450 families, namely CYP5854, CYP5855, CYP5856, CYP5858 and CYP5857, are highly bloomed. The highest number of member P450s was found in CYP5854 (48 P450s), followed by CYP5855 (36 P450s), CYP5856 (20 P450s), CYP5858 (11 P450s) and CYP5857 (10 P450s). These five P450 families contributed 88% of the total number of P450s in C. coronatus. Because of the blooming of these five P450 families, C. coronatus was found to have the lowest P450 diversity among entomopathogenic fungi. It is noteworthy that P450 blooms were not observed in other entomopathogenic fungi. Synteny and gene-structure analysis revealed that 75% of C. coronatus P450s are tandemly duplicated. These study results paved the way to understanding the nature/need for blooming of P450 families in C. coronatus.