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Bacteriophage-resistant Staphylococcus aureus mutant confers broad immunity against staphylococcal infection in mice.

Capparelli R, Nocerino N, Lanzetta R, Silipo A, Amoresano A, Giangrande C, Becker K, Blaiotta G, Evidente A, Cimmino A, Iannaccone M, Parlato M, Medaglia C, Roperto S, Roperto F, Ramunno L, Iannelli D - PLoS ONE (2010)

Bottom Line: Acquisition of phage-resistance altered several properties of A172, causing reduced growth rate, under-expression of numerous genes and production of capsular polysaccharide.The same vaccine was also effective when administered as an aerosol.The above results demonstrate that selection for phage-resistance can facilitate bacterial vaccine preparation.

View Article: PubMed Central - PubMed

Affiliation: Faculty of Biotechnology, University of Naples, Portici, Naples, Italy.

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.

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Anti-inflammatory activity of the A172 vaccine.A172 modulates transcription of the genes coding for pro-inflammatory cytokines (TNF-α, INF-γ and IL-1β) and induces transcription of the genes coding for anti-inflammatory cytokines (Il-4 and Il-6).
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pone-0011720-g007: Anti-inflammatory activity of the A172 vaccine.A172 modulates transcription of the genes coding for pro-inflammatory cytokines (TNF-α, INF-γ and IL-1β) and induces transcription of the genes coding for anti-inflammatory cytokines (Il-4 and Il-6).

Mentions: Ten mice were immunized intramuscularly with A172-HK (108 CFU/mouse). A172 modulated transcription of the genes coding for the pro-inflammatory cytokines TNF-α, IFN-γ and IL-1β, while inducing that of the genes coding for the anti-inflammatory cytokines Il-4 and Il-6, when these genes were analyzed by RT-PCR, 24 and 48 h after immunization (Figure 7). The same pattern of cytokine production was observed in mice immunized with A172-HK and 20 weeks later infected with A170 (data not shown). Given the abundant release of pro-inflammatory cytokines during S. aureus infection [36]–[37], this property of A172 is biologically relevant.


Bacteriophage-resistant Staphylococcus aureus mutant confers broad immunity against staphylococcal infection in mice.

Capparelli R, Nocerino N, Lanzetta R, Silipo A, Amoresano A, Giangrande C, Becker K, Blaiotta G, Evidente A, Cimmino A, Iannaccone M, Parlato M, Medaglia C, Roperto S, Roperto F, Ramunno L, Iannelli D - PLoS ONE (2010)

Anti-inflammatory activity of the A172 vaccine.A172 modulates transcription of the genes coding for pro-inflammatory cytokines (TNF-α, INF-γ and IL-1β) and induces transcription of the genes coding for anti-inflammatory cytokines (Il-4 and Il-6).
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC2908692&req=5

pone-0011720-g007: Anti-inflammatory activity of the A172 vaccine.A172 modulates transcription of the genes coding for pro-inflammatory cytokines (TNF-α, INF-γ and IL-1β) and induces transcription of the genes coding for anti-inflammatory cytokines (Il-4 and Il-6).
Mentions: Ten mice were immunized intramuscularly with A172-HK (108 CFU/mouse). A172 modulated transcription of the genes coding for the pro-inflammatory cytokines TNF-α, IFN-γ and IL-1β, while inducing that of the genes coding for the anti-inflammatory cytokines Il-4 and Il-6, when these genes were analyzed by RT-PCR, 24 and 48 h after immunization (Figure 7). The same pattern of cytokine production was observed in mice immunized with A172-HK and 20 weeks later infected with A170 (data not shown). Given the abundant release of pro-inflammatory cytokines during S. aureus infection [36]–[37], this property of A172 is biologically relevant.

Bottom Line: Acquisition of phage-resistance altered several properties of A172, causing reduced growth rate, under-expression of numerous genes and production of capsular polysaccharide.The same vaccine was also effective when administered as an aerosol.The above results demonstrate that selection for phage-resistance can facilitate bacterial vaccine preparation.

View Article: PubMed Central - PubMed

Affiliation: Faculty of Biotechnology, University of Naples, Portici, Naples, Italy.

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.

Show MeSH
Related in: MedlinePlus