title: Combinatorial stresses kill pathogenic Candida species.
abstract: Pathogenic microbes exist in dynamic niches and have evolved robust adaptive responses to promote survival in their hosts. The major fungal pathogens of humans, Candida albicans and Candida glabrata, are exposed to a range of environmental stresses in their hosts including osmotic, oxidative and nitrosative stresses. Significant efforts have been devoted to the characterization of the adaptive responses to each of these stresses. In the wild, cells are frequently exposed simultaneously to combinations of these stresses and yet the effects of such combinatorial stresses have not been explored. We have developed a common experimental platform to facilitate the comparison of combinatorial stress responses in C. glabrata and C. albicans. This platform is based on the growth of cells in buffered rich medium at 30°C, and was used to define relatively low, medium and high doses of osmotic (NaCl), oxidative (H(2)O(2)) and nitrosative stresses (e.g., dipropylenetriamine (DPTA)-NONOate). The effects of combinatorial stresses were compared with the corresponding individual stresses under these growth conditions. We show for the first time that certain combinations of combinatorial stress are especially potent in terms of their ability to kill C. albicans and C. glabrata and/or inhibit their growth. This was the case for combinations of osmotic plus oxidative stress and for oxidative plus nitrosative stress. We predict that combinatorial stresses may be highly significant in host defences against these pathogenic yeasts.
authors.affiliation: School of Medical Sciences, University of Aberdeen, Institute of Medical Sciences, UK.
authors.forename: Despoina
authors.initials: D
authors.lastname: Kaloriti
authors.forename: Anna
authors.initials: A
authors.lastname: Tillmann
authors.forename: Emily
authors.initials: E
authors.lastname: Cook
authors.forename: Mette
authors.initials: M
authors.lastname: Jacobsen
authors.forename: Tao
authors.initials: T
authors.lastname: You
authors.forename: Megan
authors.initials: M
authors.lastname: Lenardon
authors.forename: Lauren
authors.initials: L
authors.lastname: Ames
authors.forename: Mauricio
authors.initials: M
authors.lastname: Barahona
authors.forename: Komelapriya
authors.initials: K
authors.lastname: Chandrasekaran
authors.forename: George
authors.initials: G
authors.lastname: Coghill
authors.forename: Daniel
authors.initials: D
authors.lastname: Goodman
authors.forename: Neil A R
authors.initials: NA
authors.lastname: Gow
authors.forename: Celso
authors.initials: C
authors.lastname: Grebogi
authors.forename: Hsueh-Lui
authors.initials: HL
authors.lastname: Ho
authors.forename: Piers
authors.initials: P
authors.lastname: Ingram
authors.forename: Andrew
authors.initials: A
authors.lastname: McDonagh
authors.forename: Alessandro P S
authors.initials: AP
authors.lastname: de Moura
authors.forename: Wei
authors.initials: W
authors.lastname: Pang
authors.forename: Melanie
authors.initials: M
authors.lastname: Puttnam
authors.forename: Elahe
authors.initials: E
authors.lastname: Radmaneshfar
authors.forename: Maria Carmen
authors.initials: MC
authors.lastname: Romano
authors.forename: Daniel
authors.initials: D
authors.lastname: Silk
authors.forename: Jaroslav
authors.initials: J
authors.lastname: Stark
authors.forename: Michael
authors.initials: M
authors.lastname: Stumpf
authors.forename: Marco
authors.initials: M
authors.lastname: Thiel
authors.forename: Thomas
authors.initials: T
authors.lastname: Thorne
authors.forename: Jane
authors.initials: J
authors.lastname: Usher
authors.forename: Zhikang
authors.initials: Z
authors.lastname: Yin
authors.forename: Ken
authors.initials: K
authors.lastname: Haynes
authors.forename: Alistair J P
authors.initials: AJ
authors.lastname: Brown
mesh_terms: D002176:Candida albicans / Q000187:drug effects / Q000254:growth & development / Q000502:physiology*; D041221:Candida glabrata / Q000187:drug effects / Q000254:growth & development / Q000502:physiology*; D003470:Culture Media / Q000737:chemistry; D006801:Humans; D050296:Microbial Viability / Q000187:drug effects*; D009172:Mycology / Q000379:methods; D009603:Nitroso Compounds / Q000633:toxicity; D009997:Osmotic Pressure; D018384:Oxidative Stress; D013312:Stress, Physiological; D013696:Temperature
chemical_list: D003470:Culture Media; D009603:Nitroso Compounds