c-di-AMP /lab/aaron-whiteley/ en Cyclic di-AMP is critical for Listeria monocytogenes growth, cell wall homeostasis, and establishment of infection /lab/aaron-whiteley/2013/05/28/cyclic-di-amp-critical-listeria-monocytogenes-growth-cell-wall-homeostasis-and <span>Cyclic di-AMP is critical for Listeria monocytogenes growth, cell wall homeostasis, and establishment of infection</span> <span><span>Anonymous (not verified)</span></span> <span><time datetime="2013-05-28T00:00:00-06:00" title="Tuesday, May 28, 2013 - 00:00">Tue, 05/28/2013 - 00:00</time> </span> <div role="contentinfo" class="container ucb-article-tags" itemprop="keywords"> <span class="visually-hidden">Tags:</span> <div class="ucb-article-tag-icon" aria-hidden="true"> <i class="fa-solid fa-tags"></i> </div> <a href="/lab/aaron-whiteley/taxonomy/term/177" hreflang="en">c-di-AMP</a> <a href="/lab/aaron-whiteley/taxonomy/term/179" hreflang="en">cell wall</a> <a href="/lab/aaron-whiteley/taxonomy/term/157" hreflang="en">innate immunity</a> <a href="/lab/aaron-whiteley/taxonomy/term/151" hreflang="en">second messenger signaling</a> </div> <span>Witte CE</span> <span>,&nbsp;</span> <span>➤Whiteley AT</span> <span>,&nbsp;</span> <span>Burke TP</span> <span>,&nbsp;</span> <span>Sauer JD</span> <span>,&nbsp;</span> <span>Portnoy DA</span> <span>,&nbsp;</span> <span>Woodward JJ.</span> <div class="ucb-article-content ucb-striped-content"> <div class="container"> <div class="paragraph paragraph--type--article-content paragraph--view-mode--default"> <div class="ucb-article-content-media ucb-article-content-media-above"> <div> <div class="paragraph paragraph--type--media paragraph--view-mode--default"> </div> </div> </div> <div class="ucb-article-text d-flex align-items-center" itemprop="articleBody"> <div><p>mBio.&nbsp;2013 May 28;4(3):e00282-13. doi: 10.1128/mBio.00282-13.</p> <h3><span>Abstract</span></h3> <p>Listeria monocytogenes infection leads to robust induction of an innate immune signaling pathway referred to as the cytosolic surveillance pathway (CSP), characterized by expression of beta interferon (IFN-β) and coregulated genes. We previously identified the IFN-β stimulatory ligand as secreted cyclic di-AMP. Synthesis of c-di-AMP in<em> L. monocytogenes</em> is catalyzed by the diadenylate cyclase DacA, and multidrug resistance transporters are necessary for secretion. To identify additional bacterial factors involved in <em>L. monocytogenes</em> detection by the CSP, we performed a forward genetic screen for mutants that induced altered levels of IFN-β. One mutant that stimulated elevated levels of IFN-β harbored a transposon insertion in the gene <em>lmo0052</em>. Lmo0052, renamed here PdeA, has homology to a cyclic di-AMP phosphodiesterase, GdpP (formerly YybT), of Bacillus subtilis and is able to degrade c-di-AMP to the linear dinucleotide pApA. Reduction of c-di-AMP levels by conditional depletion of the di-adenylate cyclase DacA or overexpression of PdeA led to marked decreases in growth rates, both in vitro and in macrophages. Additionally, mutants with altered levels of c-di-AMP had different susceptibilities to peptidoglycan-targeting antibiotics, suggesting that the molecule may be involved in regulating cell wall homeostasis. During intracellular infection, increases in c-di-AMP production led to hyperactivation of the CSP. Conditional depletion of <em>dacA</em> also led to increased IFN-β expression and a concomitant increase in host cell pyroptosis, a result of increased bacteriolysis and subsequent bacterial DNA release. These data suggest that c-di-AMP coordinates bacterial growth, cell wall stability, and responses to stress and plays a crucial role in the establishment of bacterial infection.</p> <h3>Links</h3> <ul> <li>PMID:<a href="https://www.ncbi.nlm.nih.gov/pubmed/23716572" target="_blank" rel="nofollow">23716572</a></li> <li>PMCID:<a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3663569/" rel="nofollow">PMC3663569</a></li> <li>DOI:<a href="https://doi.org/10.1128/mBio.00282-13" target="_blank" rel="nofollow">10.1128/mBio.00282-13</a></li> <li><a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3663569/" rel="nofollow">Free PMC Article</a></li> </ul></div> </div> </div> </div> </div> <div>Witte CE, Whiteley AT, Burke TP, Sauer JD, Portnoy DA, Woodward JJ. | mBio. 2013</div> <h2> <div class="paragraph paragraph--type--ucb-related-articles-block paragraph--view-mode--default"> <div>Off</div> </div> </h2> <div>Traditional</div> <div>0</div> <div>On</div> <div>White</div> Tue, 28 May 2013 06:00:00 +0000 Anonymous 47 at /lab/aaron-whiteley