title: Bacteriophage-resistant Staphylococcus aureus mutant confers broad immunity against staphylococcal infection in mice.
abstract: In the presence of a bacteriophage (a bacteria-attacking virus) resistance is clearly beneficial to the bacteria. As expected in such conditions, resistant bacteria emerge rapidly. However, in the absence of the phage, resistant bacteria often display reduced fitness, compared to their sensitive counterparts. The present study explored the fitness cost associated with phage-resistance as an opportunity to isolate an attenuated strain of S. aureus. The phage-resistant strain A172 was isolated from the phage-sensitive strain A170 in the presence of the M(Sa) phage. Acquisition of phage-resistance altered several properties of A172, causing reduced growth rate, under-expression of numerous genes and production of capsular polysaccharide. In vivo, A172 modulated the transcription of the TNF-alpha, IFN-gamma and Il-1beta genes and, given intramuscularly, protected mice from a lethal dose of A170 (18/20). The heat-killed vaccine also afforded protection from heterologous methicillin-resistant S. aureus (MRSA) (8/10 mice) or vancomycin-intermediate S. aureus (VISA) (9/10 mice). The same vaccine was also effective when administered as an aerosol. Anti-A172 mouse antibodies, in the dose of 10 microl/mouse, protected the animals (10/10, in two independent experiments) from a lethal dose of A170. Consisting predominantly of the sugars glucose and galactose, the capsular polysaccharide of A172, given in the dose of 25 microg/mouse, also protected the mice (20/20) from a lethal dose of A170. The above results demonstrate that selection for phage-resistance can facilitate bacterial vaccine preparation.
authors.affiliation: Faculty of Biotechnology, University of Naples, Portici, Naples, Italy.
authors.forename: Rosanna
authors.initials: R
authors.lastname: Capparelli
authors.forename: Nunzia
authors.initials: N
authors.lastname: Nocerino
authors.forename: Rosa
authors.initials: R
authors.lastname: Lanzetta
authors.forename: Alba
authors.initials: A
authors.lastname: Silipo
authors.forename: Angela
authors.initials: A
authors.lastname: Amoresano
authors.forename: Chiara
authors.initials: C
authors.lastname: Giangrande
authors.forename: Karsten
authors.initials: K
authors.lastname: Becker
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Blaiotta
authors.forename: Antonio
authors.initials: A
authors.lastname: Evidente
authors.forename: Alessio
authors.initials: A
authors.lastname: Cimmino
authors.forename: Marco
authors.initials: M
authors.lastname: Iannaccone
authors.forename: Marianna
authors.initials: M
authors.lastname: Parlato
authors.forename: Chiara
authors.initials: C
authors.lastname: Medaglia
authors.forename: Sante
authors.initials: S
authors.lastname: Roperto
authors.forename: Franco
authors.initials: F
authors.lastname: Roperto
authors.forename: Luigi
authors.initials: L
authors.lastname: Ramunno
authors.forename: Domenico
authors.initials: D
authors.lastname: Iannelli
mesh_terms: D000117:Acetylglucosamine / Q000378:metabolism; D000818:Animals; D000907:Antibodies, Bacterial / Q000097:blood / Q000276:immunology; D001428:Bacterial Vaccines / Q000276:immunology; D001435:Bacteriophages / Q000254:growth & development / Q000502:physiology*; D002853:Chromatography, Liquid; D016521:Electrophoresis, Gel, Pulsed-Field; D005260:Female; D055624:Methicillin-Resistant Staphylococcus aureus / Q000276:immunology / Q000472:pathogenicity; D051379:Mice; D008807:Mice, Inbred BALB C; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013203:Staphylococcal Infections / Q000276:immunology* / Q000382:microbiology; D013211:Staphylococcus aureus / Q000276:immunology* / Q000472:pathogenicity / Q000821:virology*
chemical_list: D000907:Antibodies, Bacterial; D001428:Bacterial Vaccines; D000117:Acetylglucosamine