Title:
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Population structure of Candida species : spatio-temporal distribution of strain types and association with ancient Hominins
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Candida infection is a major health burden globally. Four studies were carried out to investigate the population structure, rising prevalence and coevolution of Candida spp. with humans as hosts. Molecular epidemiology using multi-locus sequence typing (MLST) of time sequential isolates from multiple body sites and micro niches addressed the question of whether single or multiple strains persist stably or are exchanged and replaced during commensal carriage and disease dissemination. Study 1: MLST data was used to identify signatures of past loss of heterozygosity (LOH) events among persistent and azole resistant isolates retrieved from patients with chronic mucocutaneous candidiasis (CMC). Study 2: The oral diseases caries and periodontitis are a major health burden world-wide resulting in tooth loss, the need for dentures and are regularly associated with the presence of Candida. MLST data support of an association of C. dubliniensis with HIV infection and periodontitis, and of C. glabratawith C. albicans with denture related stomatitis. Study 3: Dental plaque and calculus are a fecund source of biological data relevant to infection and immunity as well as diet and commensalism. Transitions in cultural practices and diet spanning recent millennia, particularly the Neolithic and Industrial revolutions, are associated with increasing prevalence of caries and periodontitis. Ancient DNA extracted from fossilised dental calculus was sequenced to determine the taxonomic diversity of oral biofilm. Candidaspp. of increased virulence and oral pathogens including Entamoeba gingivalis and Trichonomas spp. were present at these bio-cultural transitions. Study 4: C. haemuloniiand C. auris are heterothallic haploid species rising in prevalence, particularly in developing countries. De novo assembly, annotation, functional analysis and variant detection of these genomes identifies substantial gene family expansions. Expanded gene families include those involved in transmembrane metal ion and multidrug efflux and transport, and cell wall and cell membrane biogenesis and organisation.
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