title: Auxotrophic mutant of Staphylococcus aureus interferes with nasal colonization by the wild type.
abstract: Staphylococcus aureus nasal carriage is a risk factor for infection in humans, particularly in the hospital setting. Bacterial interference was used as an alternative strategy for the prevention of upper respiratory, urogenital and gastrointestinal tract infections. This study was designed to assess if the administration of a live-attenuated aroA mutant of S. aureus is useful as a potential approach to prevent transient staphylococcal nasal carriage by virulent strains. We constructed an aroA mutant of S. aureus Newman strain by homologous recombination. The auxotrophic NK41 mutant was attenuated as determined by the increase of the LD(50) after intraperitoneal challenge. In mice, previous nasal colonization with the NK41 mutant significantly reduced the number of CFU of S. aureus (HU-71 and Hde288) clinical isolates and the parental Newman strain. The NK41 mutant was unable to induce a pro-inflammatory response and to damage the invaded human respiratory epithelial cells. Moreover, the cells previously or simultaneously infected with the NK41 mutant were invaded by virulent strains in a significantly lower degree than those of the control group. In conclusion, the attenuated NK41 mutant interfered with the colonization and establishment of pathogenic strains of S. aureus, which produce severe infections.
authors.affiliation: Departamento de Microbiología, Parasitología e Inmunología, Facultad de Medicina, Universidad de Buenos Aires, Argentina.
authors.forename: María Sol
authors.initials: MS
authors.lastname: Barbagelata
authors.forename: Lucía
authors.initials: L
authors.lastname: Alvarez
authors.forename: Mariana
authors.initials: M
authors.lastname: Gordiola
authors.forename: Lorena
authors.initials: L
authors.lastname: Tuchscherr
authors.forename: Cristoff
authors.initials: C
authors.lastname: von Eiff
authors.forename: Karsten
authors.initials: K
authors.lastname: Becker
authors.forename: Daniel
authors.initials: D
authors.lastname: Sordelli
authors.forename: Fernanda
authors.initials: F
authors.lastname: Buzzola
mesh_terms: D024322:Amino Acids, Aromatic / Q000096:biosynthesis / Q000235:genetics; D000818:Animals; D000898:Antibiosis / Q000502:physiology*; D002460:Cell Line; D002478:Cells, Cultured; D051546:Cyclooxygenase 2 / Q000378:metabolism; D016207:Cytokines / Q000235:genetics; D004847:Epithelial Cells / Q000382:microbiology*; D005816:Genetic Complementation Test; D006801:Humans; D007928:Lethal Dose 50; D008297:Male; D051379:Mice; D009154:Mutation; D009297:Nasal Mucosa / Q000382:microbiology*; D011995:Recombination, Genetic; D013203:Staphylococcal Infections / Q000382:microbiology*; D013211:Staphylococcus aureus / Q000235:genetics / Q000472:pathogenicity / Q000502:physiology*; D014774:Virulence
chemical_list: D024322:Amino Acids, Aromatic; D016207:Cytokines; C077623:Ptgs2 protein, mouse; D051546:Cyclooxygenase 2