@article{TEXTUAL,
      recid = {8422},
      author = {Montgomery, Christopher P. and Boyle-Vavra, Susan and  Daum, Robert S.},
      title = {Importance of the Global Regulators &amp;lt;i&amp;gt;Agr&amp;lt;/i&amp;gt;  and &amp;lt;i&amp;gt;SaeRS&amp;lt;/i&amp;gt; in the Pathogenesis of CA-MRSA  USA300 Infection},
      journal = {PLOS ONE},
      address = {2010-12-02},
      number = {TEXTUAL},
      abstract = {&lt;p&gt;CA-MRSA infection, driven by the emergence of the  USA300 genetic background, has become epidemic in the  United States. USA300 isolates are hypervirulent, compared  with other CA- and HA-MRSA strains, in experimental models  of necrotizing pneumonia and skin infection. Interestingly,  USA300 isolates also have increased expression of core  genomic global regulatory and virulence factor genes,  including &lt;em&gt;agr&lt;/em&gt; and &lt;em&gt;saeRS&lt;/em&gt;. To test the  hypothesis that &lt;em&gt;agr&lt;/em&gt; and &lt;em&gt;saeRS&lt;/em&gt; promote the  observed hypervirulent phenotype of USA300, isogenic  deletion mutants of each were constructed in USA300. The  effects of gene deletion on expression and protein  abundance of selected downstream virulence genes were  assessed by semiquantitative real-time  reverse-transcriptase PCR (qRT-PCR) and western blot,  respectively. The effects of gene deletion were also  assessed in mouse models of necrotizing pneumonia and skin  infection. Deletion of &lt;em&gt;saeRS&lt;/em&gt;, and, to a lesser  extent, &lt;em&gt;agr&lt;/em&gt;, resulted in attenuated expression of  the genes encoding α-hemolysin (&lt;em&gt;hla&lt;/em&gt;) and the  Panton-Valentine leukocidin (&lt;em&gt;lukSF-PV&lt;/em&gt;). Despite  the differences in &lt;em&gt;hla&lt;/em&gt; transcription, the toxin  was undetectable in culture supernatants of either of the  deletion mutants. Deletion of &lt;em&gt;agr&lt;/em&gt;, but not  &lt;em&gt;saeRS&lt;/em&gt;, markedly increased the expression of the  gene encoding protein A (&lt;em&gt;spa&lt;/em&gt;), which correlated  with increased protein abundance. Each deletion mutant  demonstrated significant attenuation of virulence, compared  with wild-type USA300, in mouse models of necrotizing  pneumonia and skin infection. We conclude that &lt;em&gt;agr&lt;/em&gt;  and &lt;em&gt;saeRS&lt;/em&gt; each independently contribute to the  remarkable virulence of USA300, likely by means of their  effects on expression of secreted toxins.&lt;/p&gt;},
      url = {http://knowledge.uchicago.edu/record/8422},
}