@article{TEXTUAL, recid = {10448}, author = {Sun, Fei and Cho, Hoonsik and Jeong, Do-Won and Li, Chunling and He, Chuan and Bae, Taeok}, title = {Aureusimines in &lt;i&gt;Staphylococcus aureus&lt;/i&gt; Are Not Involved in Virulence}, journal = {PLOS ONE}, address = {2010-12-29}, number = {TEXTUAL}, abstract = {<p>Background: Recently, dipeptide aureusimines were reported to activate expression of staphylococcal virulence genes, such as alpha-hemolysin, and increase <em>S. aureus</em> virulence. Surprisingly, most of the virulence genes affected by aureusimines form part of the regulon of the SaeRS two component system (TCS), raising the possibility that SaeRS might be directly or indirectly involved in the aureusimine-dependent signaling process.</p><p>Methodology/Principal Findings: Using HPLC analyses, we confirmed that a transposon mutant of <em>ausA</em>, the gene encoding the aureusimine dipeptide synthesis enzyme, does not produce dipeptides. However, the transposon mutant showed normal hemolysis activity and alpha-hemolysin/SaeP production. Furthermore, the P1 promoter of the <em>sae</em> operon, one of the targets of the SaeRS TCS, showed normal transcription activity. Moreover, in contrast to the original report, the <em>ausA</em> transposon mutant did not exhibit attenuated virulence in an animal infection model. DNA sequencing revealed that the <em>ausA</em> deletion mutant used in the original study has an 83 nt-duplication in <em>saeS</em>. Hemolysis activity of the original mutant was restored by a plasmid carrying the <em>sae</em> operon. A mutant of the <em>sae</em> operon showed elevated resistance to chloramphenicol and erythromycin, two antibiotics widely used during staphylococcal mutagenesis. At 43°C in the presence of erythromycin and aeration, the conditions typically employed for staphylococcal mutagenesis, an <em>saeR</em> transposon mutant grew much faster than a control mutant and the <em>saeR</em> mutant was highly enriched in a mixed culture experiment.</p><p>Conclusions/Significance: Our results show that the previously reported roles of aureusimines in staphylococcal gene regulation and virulence were due to an unintended mutation in <em>saeS</em>, which was likely selected due to elevated resistance of the mutant to environmental stresses. Thus, there is no evidence indicating that the dipeptide aureusimines play a role in <em>sae</em>-mediated virulence factor production or contribute to staphylococcal virulence.</p>}, url = {http://knowledge.uchicago.edu/record/10448}, }