Comparative Genomics and the Evolution of Pathogenicity in Human Pathogenic Fungi

Abstract

Because most fungi have evolved to be free-living in the environment and because the infections they cause are usually opportunistic in nature, it is often difficult to identify specific traits that contribute to fungal pathogenesis. In recent years, there has been a surge in the number of sequenced genomes of human fungal pathogens, and comparison of these sequences has proved to be an excellent resource for exploring commonalities and differences in how these species interact with their hosts. In order to survive in the human body, fungi must be able to adapt to new nutrient sources and environmental stresses. Therefore, genes involved in carbohydrate and amino acid metabolism and transport and genes encoding secondary metabolites tend to be overrepresented in pathogenic species (e.g., Aspergillus fumigatus). However, it is clear that human commensal yeast species such as Candida albicans have also evolved a range of specific factors that facilitate direct interaction with host tissues. The evolution of virulence across the human pathogenic fungi has occurred largely through very similar mechanisms. One of the most important mechanisms is gene duplication and the expansion of gene families, particularly in subtelomeric regions. Unlike the case for prokaryotic pathogens, horizontal transfer of genes between species and other genera does not seem to have played a significant role in the evolution of fungal virulence. New sequencing technologies promise the prospect of even greater numbers of genome sequences, facilitating the sequencing of multiple genomes and transcriptomes within individual species, and will undoubtedly contribute to a deeper insight into fungal pathogenesis.

Innovation of the Parasitic Cycle of Coccidioides spp.

“…This gene is likely to be an important virulence factor in Coccidioides because it allows fungi to grow under anoxic conditions. Several fungi that are considered as obligate aerobes could be facultative anaerobes, due to their presence in the host's microhabitat, inside of an abscess or in a granuloma, if they possess and express the nir gene (Moran et al, 2011). Also, in the Coccidioides spp.…”

“…parasitic phase, genes involved in trehalose synthesis are increased. Trehalose can protect fungi against thermal stress (heat, cold), desiccation, and oxidation (Johannesson et al, 2006;Moran et al, 2011).…”

Update on Fungal Disease: From Establish Infection to Clinical Manifestation

“…Coccidioides spp. has a unique parasitic life-cycle that is not found in any other fungi that cause systemic mycoses [192]. The small spores dispersed in the air (arthroconidia) are launched into the air by the mycelium present in the soil in the southwestern United States, northern Mexico, Central America and South America.…”

“…The large parasitic cells undergo an elaborate cell wall growth process with compartmentalization of the cytoplasm leading to the formation of a multitude of endospores, smaller than the parasitic cells. These endospores grow and differentiate into second-generation spherules, also called mature spherules that escape phagocytosis as they are too large to be ingested by neutrophils, macrophages, and dendritic cells [192]. There are two clinical forms of coccidioidomycosis: the first causes an influenza-like illness, which may resolve itself or may progress to a moderate to severe disease, followed by cure of the infection and the establishment of a strong immunity against re-infection.…”

“…However, Sharpton and collaborators (2009) compared the genomes of C. immitis and C. posadasii with the nearest nonpathogenic species Uncinocarpus reesii and with the most distant pathogenic fungus H. capsulatum. Specific genes were identified in the genus Coccidioides that were: related to the spherules; involved in energy metabolism; required for the use of allantoin as a nitrogen source; related to the membrane; and others that may be involved in host-parasite interactions [192,194,195]. Furthermore, it is believed that metalloproteinases such as (Mep1), which are secreted during endosporulation phase, are able to digest the immunodominant cell surface antigen (SOWgp), preventing host recognition of the endospores during the development phase [196].…”