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Genome-wide understanding of biofilm formation phenotypic variability in C. glabrata clinical isolates
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Resumo(s)
Candida glabrata is the second major pathogen in the Candida genus, representing over 20% of all
candidemia and candiduria nosocomial infections. Phylogenetically, it is the furthest member in the
genus, being more closely related to the environmental saprophyte Saccharomyces cerevisiae3
. It is
intrinsically less susceptible to azole drugs. Emergence of resistance to the other drugs available for
candidiasis treatment is being documented.
The threat of an increasing number in fungal infections worldwide is aggravated by the high rate of
antimicrobial resistance among clinically relevant pathogens, as well as by the emergence of novel ones,
some of which are intrinsically resistant to commonly used drugs. C. glabrata is a relatively recent
pathogen and of increasing concern. Its evolution towards a higher virulence is generally associated with
strong adhesion to host’s tissues and biofilm formation. To unveil key regulators of biofilm formation
in C. glabrata, in this work, a comparative genomics approach was paired with microevolution of
clinical isolates towards a stronger biofilm formation phenotype. Specialization towards biofilm mode
of growth was verified to occur rapidly, in association to genome shortening, adhesin remodelling and
polymorphism accumulation in effectors of different regulatory levels: from epigenetic to posttranslational. Seven genes with a putative role in biofilm formation were identified and their impact
experimentally validated: SET1, EST3, SRB2, CRZ1, LMS7, RPL22A and SWF1. Those genes may be
further explored in the future as targets for biofilm disruption and markers of biofilm evolution.
Descrição
Tese de mestrado, Microbiologia Aplicada , 2023, Universidade de Lisboa, Faculdade de Ciências
Palavras-chave
Teses de mestrado - 2023