Teixeira, Miguel Nobre Parreira CachoCunha, Mónica VieiraZolotareva, Maria Olegovna2023-03-1420232022http://hdl.handle.net/10451/56645Tese de mestrado, Microbiologia Aplicada , 2023, Universidade de Lisboa, Faculdade de CiênciasCandida 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.engTeses de mestrado - 2023master thesis203501942