title: The multidrug resistance transporters CgTpo1_1 and CgTpo1_2 play a role in virulence and biofilm formation in the human pathogen Candida glabrata.
abstract: The mechanisms of persistence and virulence associated with Candida glabrata infections are poorly understood, limiting the ability to fight this fungal pathogen. In this study, the multidrug resistance transporters CgTpo1_1 and CgTpo1_2 are shown to play a role in C. glabrata virulence. The survival of the infection model Galleria mellonella, infected with C. glabrata, was found to increase upon the deletion of either CgTPO1_1 or CgTPO1_2. The underlying mechanisms were further explored. In the case of CgTpo1_1, this phenotype was found to be consistent with the observation that it confers resistance to antimicrobial peptides (AMP), such as the human AMP histatin-5. The deletion of CgTPO1_2, on the other hand, was found to limit the survival of C. glabrata cells when exposed to phagocytosis and impair biofilm formation. Interestingly, CgTPO1_2 expression was found to be up-regulated during biofilm formation, but and its deletion leads to a decreased expression of adhesin-encoding genes during biofilm formation, which is consistent with a role in biofilm formation. CgTPO1_2 expression was further seen to decrease plasma membrane potential and affect ergosterol and fatty acid content. Altogether, CgTpo1_1 and CgTpo1_2 appear to play an important role in the virulence of C. glabrata infections, being at the cross-road between multidrug resistance and pathogenesis.
authors: Department of Bioengineering, Instituto Superior Técnico, Universidade de Lisboa, Lisbon, Portugal.|Biological Sciences Research Group, IBB - Institute for Bioengineering and Biosciences, Instituto Superior Técnico, Lisbon, Portugal.
authors: Rui
authors: R
authors: Santos
authors: Department of Bioengineering, Instituto Superior Técnico, Universidade de Lisboa, Lisbon, Portugal.|Biological Sciences Research Group, IBB - Institute for Bioengineering and Biosciences, Instituto Superior Técnico, Lisbon, Portugal.
authors: Catarina
authors: C
authors: Costa
authors: Department of Bioengineering, Instituto Superior Técnico, Universidade de Lisboa, Lisbon, Portugal.|Biological Sciences Research Group, IBB - Institute for Bioengineering and Biosciences, Instituto Superior Técnico, Lisbon, Portugal.
authors: Dalila
authors: D
authors: Mil-Homens
authors: Department of Bioengineering, Instituto Superior Técnico, Universidade de Lisboa, Lisbon, Portugal.|Biological Sciences Research Group, IBB - Institute for Bioengineering and Biosciences, Instituto Superior Técnico, Lisbon, Portugal.
authors: Daniela
authors: D
authors: Romão
authors: Department of Bioengineering, Instituto Superior Técnico, Universidade de Lisboa, Lisbon, Portugal.|Biological Sciences Research Group, IBB - Institute for Bioengineering and Biosciences, Instituto Superior Técnico, Lisbon, Portugal.
authors: Carla C C R
authors: CC
authors: de Carvalho
authors: Department of Bioengineering, Instituto Superior Técnico, Universidade de Lisboa, Lisbon, Portugal.|Biological Sciences Research Group, IBB - Institute for Bioengineering and Biosciences, Instituto Superior Técnico, Lisbon, Portugal.
authors: Pedro
authors: P
authors: Pais
authors: Department of Bioengineering, Instituto Superior Técnico, Universidade de Lisboa, Lisbon, Portugal.|Biological Sciences Research Group, IBB - Institute for Bioengineering and Biosciences, Instituto Superior Técnico, Lisbon, Portugal.
authors: Nuno P
authors: NP
authors: Mira
authors: Department of Bioengineering, Instituto Superior Técnico, Universidade de Lisboa, Lisbon, Portugal.|Biological Sciences Research Group, IBB - Institute for Bioengineering and Biosciences, Instituto Superior Técnico, Lisbon, Portugal.
authors: Arsénio M
authors: AM
authors: Fialho
authors: Department of Bioengineering, Instituto Superior Técnico, Universidade de Lisboa, Lisbon, Portugal.|Biological Sciences Research Group, IBB - Institute for Bioengineering and Biosciences, Instituto Superior Técnico, Lisbon, Portugal.
authors: Miguel C
authors: 0000-0002-5676-6174
authors: MC
authors: Teixeira
mesh_terms: D000818:Animals; D000935:Antifungal Agents / Q000494:pharmacology; D018441:Biofilms; D041221:Candida glabrata / Q000187:drug effects / Q000472:pathogenicity / Q000502:physiology*; D018432:Drug Resistance, Multiple; D004875:Ergosterol / Q000378:metabolism; D005227:Fatty Acids / Q000378:metabolism; D005656:Fungal Proteins / Q000502:physiology*; D015870:Gene Expression; D005800:Genes, Fungal; D006434:Hemocytes / Q000382:microbiology; D054808:Histatins / Q000494:pharmacology; D006801:Humans; D007814:Larva / Q000382:microbiology; D050356:Lipid Metabolism; D008564:Membrane Potentials; D008826:Microbial Sensitivity Tests; D050296:Microbial Viability; D009036:Moths; D027425:ATP-Binding Cassette, Sub-Family C Proteins / Q000502:physiology*; D010587:Phagocytosis; D014774:Virulence
chemical_list: D000935:Antifungal Agents; D004875:Ergosterol; D005227:Fatty Acids; D005656:Fungal Proteins; D054808:Histatins; D027425:ATP-Binding Cassette, Sub-Family C Proteins; C068075:HTN3 protein, human
keywords: Candida glabrata; CgTpo1_1 and CgTpo1_2; Galleria mellonella; biofilm formation; virulence