Downloaded from www.microbiologyresearch.org by IP: 54.70.40.11 On: Thu, 22 Nov 2018 05:23:56 The Candida albicans Hwp2p can complement the lack of filamentation of a Saccharomyces cerevisiae flo11 null strain Samer S. Younes and Roy A. Khalaf Correspondence Roy A. Khalaf roy.khalaf@lau.edu.lb Received 20 February 2013 Accepted 26 March 2013 Natural Sciences Department, Lebanese American University, PO Box 36, Byblos, Lebanon The opportunistic fungal pathogen Candida albicans is one of the leading agents of life- threatening infections affecting immunocompromised individuals. Many factors make C. albicans a successful pathogen. These include the ability to switch between yeast and invasive hyphal morphologies in addition to an arsenal of cell wall virulence factors such as lipases, proteases, dismutases and adhesins that promote the attachment to the host, a prerequisite for invasive growth. We have previously characterized Hwp2, a C. albicans cell wall protein which we found necessary for proper oxidative stress, biofilm formation and adhesion to host cells. Baker’s yeast Saccharomyces cerevisiae also possesses adhesins that promote aggregation and flocculence. Flo11 is one such adhesin that has sequence similarity to Hwp2. Here we determined that transforming an HWP2 cassette can complement the lack of filamentation of an S. cerevisiae flo11 null strain and impart on S. cerevisiae adhesive properties similar to those of a pathogen. INTRODUCTION The asexual diploid opportunistic fungus Candida albicans is the leading causative agents of fungal infection and the fourth most isolated pathogen in hospital patients (Mohan das & Ballal, 2008). At certain disease states when a patient is immunocompromised, C. albicans has the ability to overcome host defences. Physiological states such as diabetes, pregnancy, neutropenia and immunosuppressive therapy predispose individuals to serious candidiasis encompassing infections that range from superficial, such as oral thrush and vaginitis, to systemic and potentially life-threatening diseases. Mortality rates associated with candidaemia and disseminated candidiasis are close to 50 % with treatment costs in the billions of dollars per year (Viudes et al., 2002). Many factors allow C. albicans to be a successful pathogen. These include its ability to undergo dimorphic switching from the yeast form to the invasive, filamentous and more adhesive hyphal form, the form found in diseased individuals, with an additional pseudohyphal form. In addition C. albicans has evolved a wide arsenal of cell-wall- secreted virulence factors. These include phopholipases, lipases, proteases and dismutases involved in digesting or distorting host cell membranes and contributing to host tissue invasion in addition to combating reactive oxygen species generated by the host immune system (Ibrahim et al., 1995). Another set of virulence factors are the adhesins required for attachment to the host, a prerequisite for invasion. Most characterized adhesins such as Hwp1, Hwp2 and members of the agglutinin like sequence (Als) protein family attach to the cell wall by means of a preformed GPI-anchor added postranslationally to the C terminus. Many adhesins studied to date have common structural features, with an N-terminal globular immuno- globulin-like or lectin domain, a serine–threonine-rich region containing conserved repeats and a C-terminal glycosylated stalk region that extends the active site from the cell wall surface (Otoo et al., 2008). Adherence to the host cell is the first step in the process of infection in C. albicans. Besides mediating yeast-to-host tissue adherence, Als proteins can also promote yeast aggregation which has amyloid-like characteristics. As antigenic determinants, deletion of many of these adhesins rendered the mutant cell significantly defective in adhesion and virulence (Yang 2003; Hayek et al., 2010). C. albicans is distantly related to Saccharomyces cerevisiae and has a sizeable number of adhesins. Given that S. cerevisiae is a non-pathogenic yeast, the adhesins do not mediate virulence but mainly flocculation and aggregation. One notable member of this family is Flo11, a cell-surface- bound mucin-like protein containing serine–threonine- rich conserved repeats found to be necessary for blastos- pore–pseudohyphal switching in addition to flocculation and aggregation. Flo11 is also necessary for diploid pseudohyphal formation, haploid agar invasion and biofilm formation (Dranginis et al., 2007; Lambrechts et al., 1996). In C. albicans the Hwp2 adhesin shares sequence similarity with Flo11 and a hwp2-null mutant showed similar phenotypes to a flo11-null mutant as the strain was afilamentous and hence non-invasive on solid media such as Sabouraud and cornmeal agar (Hayek et al., 2010). Furthermore we found that adherence of the mutant Microbiology (2013), 159, 1160–1164 DOI 10.1099/mic.0.067249-0 1160 067249 G 2013 SGM Printed in Great Britain