title: Targeted gene disruption in Candida parapsilosis demonstrates a role for CPAR2_404800 in adhesion to a biotic surface and in a murine model of ascending urinary tract infection.
abstract: Candida parapsilosis is an emerging opportunistic pathogen, second in frequency only to C. albicans and commonly associated with both mucosal and systemic infections. Adhesion to biotic surfaces is a key step for the development of mycoses. The C. parapsilosis genome encodes 5 predicted agglutinin-like sequence proteins and their precise role in the adhesion process still remains to be elucidated. In this study, we focused on the putative adhesin Cpar2_404800, in view of its high homology to the most important adhesion molecule in C. albicans. Two independent lineages of C. parapsilosis CPAR2_404800 heterozygous and null mutants were obtained by site-specific deletion. CPAR2_404800 mutants did not differ from wild-type strain in terms of in vitro growth or in their ability to undergo morphogenesis. However, when compared for adhesion to a biotic surface, CPAR2_404800 null mutants exhibited a marked reduction in their adhesion to buccal epithelial cells (>60% reduction of adhesion index). Reintroduction of one copy of CPAR2_404800 gene in the null background restored wild type phenotype. A murine model of urinary tract infection was used to elucidate the in vivo contribution of CPAR2_404800. A 0.5 and 1 log10 reduction in colony forming unit numbers (per gram) was observed respectively in bladder and kidneys obtained from mice infected with null mutant compared to wild-type infected ones. Taken together, these findings provide the first evidence for a direct role of CPAR2_404800 in C. parapsilosis adhesion to host surfaces and demonstrate its contribution to the pathogenesis of murine urinary candidiasis.
authors.affiliation: a Department of Biology ; Genetic Unit; University of Pisa ; Pisa , Italy.
authors.forename: Alessia
authors.initials: A
authors.lastname: Bertini
authors.affiliation: a Department of Biology ; Genetic Unit; University of Pisa ; Pisa , Italy.
authors.forename: Marina
authors.initials: M
authors.lastname: Zoppo
authors.affiliation: a Department of Biology ; Genetic Unit; University of Pisa ; Pisa , Italy.
authors.forename: Lisa
authors.initials: L
authors.lastname: Lombardi
authors.affiliation: a Department of Biology ; Genetic Unit; University of Pisa ; Pisa , Italy.
authors.forename: Cosmeri
authors.initials: C
authors.lastname: Rizzato
authors.affiliation: b Institute of Microbiology; Catholic University of the Sacred Heart ; Rome , Italy.
authors.forename: Elena
authors.initials: E
authors.lastname: De Carolis
authors.affiliation: b Institute of Microbiology; Catholic University of the Sacred Heart ; Rome , Italy.
authors.forename: Antonietta
authors.initials: A
authors.lastname: Vella
authors.affiliation: b Institute of Microbiology; Catholic University of the Sacred Heart ; Rome , Italy.
authors.forename: Riccardo
authors.initials: R
authors.lastname: Torelli
authors.affiliation: b Institute of Microbiology; Catholic University of the Sacred Heart ; Rome , Italy.
authors.forename: Maurizio
authors.initials: M
authors.lastname: Sanguinetti
authors.affiliation: a Department of Biology ; Genetic Unit; University of Pisa ; Pisa , Italy.
authors.forename: Arianna
authors.initials: A
authors.lastname: Tavanti
mesh_terms: D000818:Animals; D002175:Candida / Q000235:genetics* / Q000254:growth & development / Q000472:pathogenicity / Q000502:physiology*; D002177:Candidiasis / Q000382:microbiology*; D002448:Cell Adhesion; D004195:Disease Models, Animal; D004847:Epithelial Cells / Q000382:microbiology*; D005800:Genes, Fungal; D054884:Host-Pathogen Interactions; D007668:Kidney / Q000382:microbiology; D051379:Mice; D009036:Moths / Q000382:microbiology*; D009061:Mouth Mucosa / Q000166:cytology / Q000382:microbiology; D009154:Mutation; D010641:Phenotype; D001743:Urinary Bladder / Q000382:microbiology; D014552:Urinary Tract Infections / Q000382:microbiology*; D014774:Virulence
keywords: ALS-like genes; Candida parapsilosis; Galleria mellonella; adhesion; host-pathogen interaction; murine urinary infection; virulence factors