title: Defining the Roles of the Cation Diffusion Facilitators in Fe2+/Zn2+Homeostasis and Establishment of Their Participation in Virulence inPseudomonas aeruginosa.
abstract: Transporters of the cation diffusion facilitator (CDF) family form dimers that export transition metals from the cytosol. The opportunistic pathogenPseudomonas aeruginosaencodes three homologous CDF genes,czcD(PA0397),aitP(PA1297), andyiiP(PA3963). The three proteins are required for virulence in a plant host model. Disruption of theaitPgene leads to higher Fe2+and Co2+sensitivity together with an intracellular accumulation of these ions and to a decreased survival in presence of H2O2. Strains lackingczcDandyiiPshowed low Zn2+sensitivity. However, in iron-rich media and in the presence of Zn2+these strains secreted higher levels of the iron chelator pyoverdine. Disruption ofczcDandyiiPin a non-pyoverdine producer strain and lacking the Zn2+-transporting ATPase, increased the Zn2+sensitivity and the accumulation of this ion. Most importantly, independent of the pyoverdine production strains lacking CzcD or YiiP, presented lower resistance to imipenem, ciprofloxacin, chloramphenicol, and gentamicin. These observations correlated with a lower survival rate upon EDTA-lysozyme treatment and overexpression of OprN and OprD porins. We hypothesize that while AitP is an Fe2+/Co2+efflux transporter required for Fe2+homeostasis, and ultimately redox stress handling, CzcD, and YiiP export Zn2+to the periplasm for proper Zn2+-dependent signaling regulating outer membrane stability and therefore antibiotic tolerance.
authors.affiliation: Consejo Nacional de Investigaciones Científicas y Técnicas, Instituto de Investigación Médica Mercedes y Martín Ferreyra, Universidad Nacional de Córdoba Córdoba, Argentina.
authors.forename: Agostina
authors.initials: A
authors.lastname: Salusso
authors.affiliation: Consejo Nacional de Investigaciones Científicas y Técnicas, Instituto de Investigación Médica Mercedes y Martín Ferreyra, Universidad Nacional de Córdoba Córdoba, Argentina.
authors.forename: Daniel
authors.initials: D
authors.lastname: Raimunda
mesh_terms: D002413:Cations, Divalent / Q000378:metabolism*; D006706:Homeostasis; D054884:Host-Pathogen Interactions; D007501:Iron / Q000378:metabolism*; D050296:Microbial Viability; D010935:Plant Diseases / Q000382:microbiology*; D010944:Plants / Q000382:microbiology; D011550:Pseudomonas aeruginosa / Q000378:metabolism / Q000502:physiology*; D014774:Virulence; D015032:Zinc / Q000378:metabolism*
chemical_list: D002413:Cations, Divalent; D007501:Iron; D015032:Zinc
keywords: cation diffusion facilitator; efflux; iron; transition metal homeostasis; virulence; zinc