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Autoinducer
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<h2 id="discovery">Discovery</h2> <p>The term <i>autoinduction</i> was first coined in 1970, when it was observed that the <a href="/facts/Bioluminescence/IlzgyV4E">bioluminescent</a> marine bacterium <i><a href="/facts/Vibrio_fischeri/tFMLns6E">Vibrio fischeri</a></i> produced a luminescent enzyme (<a href="/facts/Luciferase/7yl8dytU">luciferase</a>) only when cultures had reached a threshold population density.<a class="footnote-ref" id="fnref:5" href="#fn:5"><sup>5</sup></a> At low cell concentrations, <i>V. fischeri</i> did not express the luciferase gene. However, during the cultures’ exponential growth phase, the luciferase gene was rapidly activated. This phenomenon was called autoinduction because it involved a molecule (the autoinducer) produced by the bacteria themselves that accumulated in the growth medium and induced the synthesis of components of the luminescence system.<a class="footnote-ref" id="fnref:6" href="#fn:6"><sup>6</sup></a> Subsequent research revealed that the actual autoinducer used by <i>V. fischeri</i> is an <a href="/facts/Acylated_homoserine_lactone/PyA3gE6t">acylated homoserine lactone</a> (AHL) signaling molecule. </p> <h2 id="mechanism">Mechanism</h2> <p>In the most simplified quorum sensing systems, bacteria only need two components to make use of autoinducers. They need a way to produce a signal and a way to respond to that signal. These cellular processes are often tightly coordinated and involve changes in gene expression. The production of autoinducers generally increases as bacterial cell densities increase. Most signals are produced intracellularly and are subsequently secreted in the extracellular environment. Detection of autoinducers often involves diffusion back into cells and binding to specific <a href="/facts/Receptor_(biochemistry)/tjTAC76a">receptors</a>. Usually, binding of autoinducers to receptors does not occur until a threshold concentration of autoinducers is achieved. Once this has occurred, bound receptors alter gene expression either directly or indirectly. Some receptors are <a href="/facts/Transcription_factor/wro0DPHe">transcription factors</a> themselves, while others relay signals to downstream transcription factors. In many cases, autoinducers participate in forward feedback loops, whereby a small initial concentration of an autoinducer amplifies the production of that same chemical signal to much higher levels. </p> <h2 id="classes">Classes</h2> <h3>Acylated homoserine lactones</h3> <p>Primarily produced by Gram-negative bacteria, <a href="/facts/Acylated_homoserine_lactone/PyA3gE6t">acylated homoserine lactones</a> (AHLs) are a class of small neutral lipid molecules composed of a homoserine lactone ring with an acyl chain.<a class="footnote-ref" id="fnref:7" href="#fn:7"><sup>7</sup></a> AHLs produced by different species of Gram-negative bacteria vary in the length and composition of the acyl side chain, which often contains 4 to 18 carbon atoms.<a class="footnote-ref" id="fnref:8" href="#fn:8"><sup>8</sup></a> AHLs are synthesized by AHL synthases. They diffuse in and out of cells by both <a href="/facts/Passive_transport/pH9lfpaW">passive transport</a> and <a href="/facts/Active_transport/7EAcsfb2">active transport</a> mechanisms.<a class="footnote-ref" id="fnref:9" href="#fn:9"><sup>9</sup></a> Receptors for AHLs include a number of transcriptional regulators called "R proteins," which function as DNA binding transcription factors or sensor <a href="/facts/Kinases/dhlHpjnD">kinases</a>.<a class="footnote-ref" id="fnref:10" href="#fn:10"><sup>10</sup></a><a class="footnote-ref" id="fnref:11" href="#fn:11"><sup>11</sup></a> </p> <h3>Peptides</h3> <p>Gram-positive bacteria that participate in quorum sensing typically use secreted <a href="/facts/Oligopeptides/rM2AHGNV">oligopeptides</a> as autoinducers. Peptide autoinducers usually result from <a href="/facts/Posttranslational_modification/KMUayTIc">posttranslational modification</a> of a larger precursor molecule.<a class="footnote-ref" id="fnref:12" href="#fn:12"><sup>12</sup></a> In many Gram-positive bacteria, secretion of peptides requires specialized export mechanisms. For example, some peptide autoinducers are secreted by <a href="/facts/ATP-binding_cassette_transporter/aXPf4sA9">ATP-binding cassette transporters</a> that couple proteolytic processing and cellular export.<a class="footnote-ref" id="fnref:13" href="#fn:13"><sup>13</sup></a> Following secretion, peptide autoinducers accumulate in extracellular environments. Once a threshold level of signal is reached, a histidine sensor kinase protein of a <a href="/facts/Two-component_regulatory_system/VP6hvFTe">two-component regulatory system</a> detects it and a signal is relayed into the cell.<a class="footnote-ref" id="fnref:14" href="#fn:14"><sup>14</sup></a> As with AHLs, the signal ultimately ends up altering gene expression. Unlike some AHLs, however, most oligopeptides do not act as transcription factors themselves. </p> <h3>Furanosyl borate diester</h3> <p>The free-living bioluminescent marine bacterium, <i><a href="/facts/Vibrio_harveyi/TLQ4zq77">Vibrio harveyi</a></i>, uses another signaling molecule in addition to an acylated homoserine lactone. This molecule, termed <a href="/facts/Autoinducer-2/26SE9e7f">Autoinducer-2</a> (or AI-2), is a furanosyl borate diester.<a class="footnote-ref" id="fnref:15" href="#fn:15"><sup>15</sup></a> AI-2, which is also produced and used by a number of Gram-negative and Gram-positive bacteria, is believed to be an evolutionary link between the two major types of quorum sensing circuits.<a class="footnote-ref" id="fnref:16" href="#fn:16"><sup>16</sup></a> </p> <h2 id="in-gram-negative-bacteria">In gram-negative bacteria</h2> <p>As mentioned, Gram-negative bacteria primarily use acylated homoserine lactones (AHLs) as autoinducer molecules. The minimum quorum sensing circuit in Gram-negative bacteria consists of a protein that synthesizes an AHL and a second, different protein that detects it and causes a change in gene expression.<a class="footnote-ref" id="fnref:17" href="#fn:17"><sup>17</sup></a> First identified in <i>V. fischeri</i>, these two such proteins are LuxI and LuxR, respectively.<a class="footnote-ref" id="fnref:18" href="#fn:18"><sup>18</sup></a><a class="footnote-ref" id="fnref:19" href="#fn:19"><sup>19</sup></a> Other Gram-negative bacteria use LuxI-like and LuxR-like proteins (<a href="/facts/Homologous_series/7PKCuvzm">homologs</a>), suggesting a high degree of <a href="/facts/Evolutionary_conservation/YAxy2Xa2">evolutionary conservation</a>. However, among Gram-negatives, the LuxI/LuxI-type circuit has been modified in different species. Described in more detail below, these modifications reflect bacterial <a href="/facts/Adaptations/5K2gNpDB">adaptations</a> to grow and respond to particular <a href="/facts/Ecological_niche/YnhNkL2e">niche</a> environments.<a class="footnote-ref" id="fnref:20" href="#fn:20"><sup>20</sup></a> </p> <h3><i>Vibrio fischeri</i>: bioluminescence</h3> <p>Ecologically, <i>V. fischeri</i> is known to have <a href="/facts/Symbiotic/MrBArRGa">symbiotic</a> associations with a number of eukaryotic hosts, including the Hawaiian Bobtail Squid (<i><a href="/facts/Euprymna_scolopes/njqolach">Euprymna scolopes</a></i>).<a class="footnote-ref" id="fnref:21" href="#fn:21"><sup>21</sup></a> In this relationship, the squid host maintains the bacteria in specialized light organs. The host provides a safe, nutrient rich environment for the bacteria and in turn, the bacteria provide light. Although bioluminescence can be used for mating and other purposes, in <i>E. scolopes</i> it is used for <a href="/facts/Counter_illumination/8dVECjUb">counter illumination</a> to avoid predation.<a class="footnote-ref" id="fnref:22" href="#fn:22"><sup>22</sup></a> </p><p>The autoinducer molecule used by <i>V. fischeri</i> is N-(3-oxohexanoyl)-homoserine lactone.<a class="footnote-ref" id="fnref:23" href="#fn:23"><sup>23</sup></a> This molecule is produced in the cytoplasm by the LuxI synthase enzyme and is secreted through the cell membrane into the extracellular environment.<a class="footnote-ref" id="fnref:24" href="#fn:24"><sup>24</sup></a> As is true of most autoinducers, the environmental concentration of N-(3-oxohexanoyl)-homoserine lactone is the same as the intracellular concentration within each cell.<a class="footnote-ref" id="fnref:25" href="#fn:25"><sup>25</sup></a> N-(3-oxohexanoyl)-homoserine lactone eventually diffuses back into cells where it is recognized by LuxR once a threshold concentration (~10 μg/ml) has been reached.<a class="footnote-ref" id="fnref:26" href="#fn:26"><sup>26</sup></a> LuxR binds the autoinducer and directly activates transcription of the <i>luxICDABE</i> operon.<a class="footnote-ref" id="fnref:27" href="#fn:27"><sup>27</sup></a> This results in an exponential increase in both the production of autoinducer and in bioluminescence. LuxR bound by autoinducer also inhibits the expression of <i>luxR</i>, which is thought to provide a <a href="/facts/Negative_feedback/G9byVgpN">negative feedback</a> compensatory mechanism to tightly control levels of the bioluminescence genes.<a class="footnote-ref" id="fnref:28" href="#fn:28"><sup>28</sup></a> </p> <h3><i>Pseudomonas aeruginosa</i>: virulence and antibiotic production</h3> <p><i><a href="/facts/Pseudomonas_aeruginosa/HBhyIxAn">P. aeruginosa</a></i> is an <a href="/facts/Opportunistic_infection/d6ndMynw">opportunistic</a> <a href="/facts/Human_pathogen/HXytDGzC">human pathogen</a> associated with <a href="/facts/Cystic_fibrosis/tlNK5BAH">cystic fibrosis</a>. In <i>P. aeruginosa</i> infections, quorum sensing is critical for biofilm formation and pathogenicity.<a class="footnote-ref" id="fnref:29" href="#fn:29"><sup>29</sup></a> <i>P. aeruginosa</i> contains two pairs of LuxI/LuxR homologs, LasI/LasR and RhlI, RhlR.<a class="footnote-ref" id="fnref:30" href="#fn:30"><sup>30</sup></a><a class="footnote-ref" id="fnref:31" href="#fn:31"><sup>31</sup></a> LasI and RhlI are synthase enzymes that catalyze the synthesis of N-(3-oxododecanoyl)-homoserine lactone and N-(butyryl)-homoserine lactone, respectively.<a class="footnote-ref" id="fnref:32" href="#fn:32"><sup>32</sup></a><a class="footnote-ref" id="fnref:33" href="#fn:33"><sup>33</sup></a> The LasI/LasR and the RhlI/RhlR circuits function in tandem to regulate the expression of a number of virulence genes. At a threshold concentration, LasR binds N-(3-oxododecanoyl)-homoserine lactone. Together this bound complex promotes the expression of virulence factors that are responsible for early stages of the infection process.<a class="footnote-ref" id="fnref:34" href="#fn:34"><sup>34</sup></a> </p><p>LasR bound by its autoinducer also activates the expression of the RhlI/RhlR system in <i>P. aeruginosa</i>.<a class="footnote-ref" id="fnref:35" href="#fn:35"><sup>35</sup></a> This causes the expression of RhlR which then binds its autoinducer, N-(butryl)-homoserine lactone. In turn, autoinducer-bound RhlR activates a second class of genes involved in later stages of infection, including genes needed for antibiotic production.<a class="footnote-ref" id="fnref:36" href="#fn:36"><sup>36</sup></a> Presumably, antibiotic production by <i>P. aeruginosa</i> is used to prevent opportunistic infections by other bacterial species. N-(3-oxododecanoyl)-homoserine lactone prevents binding between N-(butryl)-homoserine lactone and its cognate regulator, RhlR.<a class="footnote-ref" id="fnref:37" href="#fn:37"><sup>37</sup></a> It is believed that this control mechanism allows <i>P. aeruginosa</i> to initiate the quorum-sensing cascades sequentially and in the appropriate order so that a proper infection cycle can ensue.<a class="footnote-ref" id="fnref:38" href="#fn:38"><sup>38</sup></a> </p> <h3>Other gram-negative autoinducers</h3> <ul><li><i>P. aeruginosa</i> also uses 2-heptyl-3-hydroxy-4-quinolone (PQS) for quorum sensing.<a class="footnote-ref" id="fnref:39" href="#fn:39"><sup>39</sup></a> This molecule is noteworthy because it does not belong to the homoserine lactone class of autoinducers. PQS is believed to provide an additional regulatory link between the Las and Rhl circuits involved in virulence and infection.</li> <li><i><a href="/facts/Agrobacterium_tumefaciens/aN1LUWQY">Agrobacterium tumefaciens</a></i> is a <a href="/facts/Plant_pathogen/h6DTufWF">plant pathogen</a> that induces tumors on susceptible hosts. Infection by <i>A. tumefaciens</i> involves the transfer of an <a href="/facts/Oncogenic/PC8wc1Mf">oncogenic</a> plasmid from the bacterium to the host cell nucleus, while quorum sensing controls the conjugal transfer of plasmids between bacteria.<a class="footnote-ref" id="fnref:40" href="#fn:40"><sup>40</sup></a> <a href="/facts/Bacterial_conjugation/WfeyKYC4">Conjugation</a>, on the other hand, requires the HSL autoinducer, N-(3-oxooctanoyl)-homoserine lactone.<a class="footnote-ref" id="fnref:41" href="#fn:41"><sup>41</sup></a></li> <li><i><a href="/facts/Erwinia_carotovora/RPPdsf3E">Erwinia carotovora</a></i> is another plant pathogen that causes soft-rot disease. These bacteria secrete <a href="/facts/Cellulases/B5ppt817">cellulases</a> and pectinases, which are enzymes that degrade plant cell walls.<a class="footnote-ref" id="fnref:42" href="#fn:42"><sup>42</sup></a> ExpI/ExpR are LuxI/LuxR homologs in <i>E. carotovora</i> believed to control secretion of these enzymes only when a high enough local cell density is achieved. The autoinducer involved in quorum sensing in <i>E. carotovora</i> is N-(3-oxohexanoyl)-L-homoserine lactone.<a class="footnote-ref" id="fnref:43" href="#fn:43"><sup>43</sup></a></li></ul> <h2 id="in-gram-positive-bacteria">In gram-positive bacteria</h2> <p>Whereas Gram-negative bacteria primarily use acylated homoserine lactones, Gram-positive bacteria generally use oligopeptides as autoinducers for quorum sensing. These molecules are often synthesized as larger polypeptides that are cleaved post-translationally to produce "processed" peptides. Unlike AHLs that can freely diffuse across cell membranes, peptide autoinducers usually require specialized transport mechanisms (often ABC transporters). Additionally, they do not freely diffuse back into cells, so bacteria that use them must have mechanisms to detect them in their extracellular environments. Most Gram-positive bacteria use a two-component signaling mechanism in quorum sensing. Secreted peptide autoinducers accumulate as a function of cell density. Once a quorum level of autoinducer is achieved, its interaction with a sensor kinase at the cell membrane initiates a series of <a href="/facts/Phosphorylation/LXUEEeIL">phosphorylation</a> events that culminate in the phosphorylation of a regulator protein intracellularly.<a class="footnote-ref" id="fnref:44" href="#fn:44"><sup>44</sup></a> This regulator protein subsequently functions as a transcription factor and alters gene expression. Similar to Gram-negative bacteria, the autoinduction and quorum sensing system in Gram-positive bacteria is conserved, but again, individual species have tailored specific aspects for surviving and communicating in unique niche environments. </p> <h3><i>Streptococcus pneumoniae</i>: competence</h3> <p><i><a href="/facts/S._pneumoniae/B5XxK27j">S. pneumoniae</a></i> is human pathogenic bacterium in which the process of genetic <a href="/facts/Transformation_(genetics)/n82cCRCu">transformation</a> was first described in the 1930s.<a class="footnote-ref" id="fnref:45" href="#fn:45"><sup>45</sup></a> In order for a bacterium to take up exogenous DNA from its surroundings, it must become <a href="/facts/Competence_(biology)/R4xxnX8M">competent</a>. In <i>S. pneumoniae</i>, a number of complex events must occur to achieve a competent state, but it is believed that quorum sensing plays a role.<a class="footnote-ref" id="fnref:46" href="#fn:46"><sup>46</sup></a> <a href="/facts/Competence_stimulating_peptide/zjXyI7TJ">Competence stimulating peptide</a> (CSP) is a 17-amino acid peptide autoinducer required for competency and subsequent genetic transformation.<a class="footnote-ref" id="fnref:47" href="#fn:47"><sup>47</sup></a> CSP is produced by proteolytic cleavage of a 41-amino acid precursor peptide (ComC); is secreted by an ABC transporter (ComAB); and is detected by a sensor kinase protein (ComD) once it has reached a threshold concentration.<a class="footnote-ref" id="fnref:48" href="#fn:48"><sup>48</sup></a><a class="footnote-ref" id="fnref:49" href="#fn:49"><sup>49</sup></a><a class="footnote-ref" id="fnref:50" href="#fn:50"><sup>50</sup></a> Detection is followed by autophosphorylation of ComD, which in turn, phosphorylates ComE. ComE is a response regulator responsible for activating transcription of <i>comX</i>, the product of which is required to activate transcription of a number of other genes involved in the development of competence.<a class="footnote-ref" id="fnref:51" href="#fn:51"><sup>51</sup></a> </p> <h3><i>Bacillus subtilis</i>: competence & sporulation</h3> <p><a href="/facts/B._subtilis/KA8AodsE">B. subtilis</a> is a soil-dwelling microbe that uses quorum sensing to regulate two different biological processes: competence and <a href="/facts/Sporulation/6qDRdcrs">sporulation</a>. During stationary growth phase when B. subtilis are at high cell density, approximately 10% of the cells in a population are induced to become competent. It is believed that this subpopulation becomes competent to take up DNA that could potentially be used for the repair of damaged (mutated) <a href="/facts/Chromosomes/FRGf11FC">chromosomes</a>.<a class="footnote-ref" id="fnref:52" href="#fn:52"><sup>52</sup></a> ComX (also known as competence factor) is a 10-amino acid peptide that is processed from a 55-amino acid peptide precursor.<a class="footnote-ref" id="fnref:53" href="#fn:53"><sup>53</sup></a> Like most autoinducers, ComX is secreted and accumulates as a function of cell density. Once a threshold extracellular level is achieved, ComX is detected by a two-component ComP/ComA sensor kinase/response regulator pair.<a class="footnote-ref" id="fnref:54" href="#fn:54"><sup>54</sup></a> Phosphorylation of ComA activates the expression of <i>comS</i> gene, ComS inhibits the degradation of ComK, and finally ComK activates the expression of a number of genes required for competence.<a class="footnote-ref" id="fnref:55" href="#fn:55"><sup>55</sup></a> </p><p>Sporulation, on the other hand, is a physiological response of <i>B. subtilis</i> to depletion of nutrients within a particular environment. It is also regulated by extracellular signaling. When <i>B. subtilis</i> populations sense waning conditions, they respond by undergoing asymmetric cell division.<a class="footnote-ref" id="fnref:56" href="#fn:56"><sup>56</sup></a> This ultimately produces spores that are adapted for dispersal and survival in unfavorable conditions. Sporulation in <i>B. subtilis</i> is mediated by CSF (sporulation factor), a pentapeptide cleaved from the precursor peptide PhrC.<a class="footnote-ref" id="fnref:57" href="#fn:57"><sup>57</sup></a> CSF is secreted into the extracellular environment and is taken back up into cells via the ABC transporter Opp where it acts intracellularly.<a class="footnote-ref" id="fnref:58" href="#fn:58"><sup>58</sup></a> While low internal concentrations of CSF contribute to competence, high concentrations induce sporulation. CSF inhibits a phosphatase, RabB, which increases the activity of Spo0A, favoring a switch in commitment from competence to the sporulation pathway<a class="footnote-ref" id="fnref:59" href="#fn:59"><sup>59</sup></a> </p> <h2 id="references">References</h2> <ol> <li id="fn:1"><p>"How Quorum Sensing Works". asm.org. American Society for Microbiology. June 12, 2020. Retrieved July 9, 2024. <a href="https://asm.org/articles/2020/june/how-quorum-sensing-works" target="_blank">https://asm.org/articles/2020/june/how-quorum-sensing-works</a> <a href="#fnref:1" class="footnote-back-ref">↩</a></p></li> <li id="fn:2"><p>Davies, D.G., Parsek, M.R., Pearson, J.P., Iglewski, B.H., Costerton, J.W., Greenberg, E.P. (1998 April 10). The involvement of cell-to-cell signals in the development of a bacterial biofilm. Science. Retrieved from https://www.science.org/doi/abs/10.1126/science.280.5361.295. <a href="https://www.science.org/doi/abs/10.1126/science.280.5361.295" target="_blank">https://www.science.org/doi/abs/10.1126/science.280.5361.295</a> <a href="#fnref:2" class="footnote-back-ref">↩</a></p></li> <li id="fn:3"><p>"Bacteria_communications". <a href="http://cronodon.com/BioTech/Bacteria_communications.html" target="_blank">http://cronodon.com/BioTech/Bacteria_communications.html</a> <a href="#fnref:3" class="footnote-back-ref">↩</a></p></li> <li id="fn:4"><p>Miller, M.B.; Bassler, B.L. (2001). "Quorum Sensing in Bacteria". Annu. Rev. Microbiol. 55: 165–199. doi:10.1146/annurev.micro.55.1.165. PMID 11544353. <a href="/wiki/Doi_(identifier)" target="_blank">/wiki/Doi_(identifier)</a> <a href="#fnref:4" class="footnote-back-ref">↩</a></p></li> <li id="fn:5"><p>Nealson, K.; Platt, T.; Hastings, J.W. (1970). "Cellular Control of the Synthesis and Activity of the Bacterial Luminescent System". J. Bacteriol. 104 (1): 313–322. doi:10.1128/jb.104.1.313-322.1970. PMC 248216. PMID 5473898. <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC248216" target="_blank">https://www.ncbi.nlm.nih.gov/pmc/articles/PMC248216</a> <a href="#fnref:5" class="footnote-back-ref">↩</a></p></li> <li id="fn:6"><p>Nealson, K.H.; Hastings, J.W. (1979). "Bacterial bioluminescence: its control and ecological significance". Microbiol. Rev. 43 (4): 496–518. doi:10.1128/mmbr.43.4.496-518.1979. PMC 281490. PMID 396467. <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC281490" target="_blank">https://www.ncbi.nlm.nih.gov/pmc/articles/PMC281490</a> <a href="#fnref:6" class="footnote-back-ref">↩</a></p></li> <li id="fn:7"><p>Churchill, M.E.; Chen, L. (2011). "Structural basis of acyl-homoserine lactone-dependent signaling". Chem. Rev. 111 (1): 68–85. doi:10.1021/cr1000817. PMC 3494288. PMID 21125993. <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3494288" target="_blank">https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3494288</a> <a href="#fnref:7" class="footnote-back-ref">↩</a></p></li> <li id="fn:8"><p>Marketon, M.M.; Gronquist, M.R.; Eberhard, A.; González, J.E. (2002). "Characterization of the Sinorhizobium meliloti sinR/sinI locus and the production of novel N-acyl homoserine lactones". J. Bacteriol. 184 (20): 5686–5695. doi:10.1128/jb.184.20.5686-5695.2002. PMC 139616. PMID 12270827. <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC139616" target="_blank">https://www.ncbi.nlm.nih.gov/pmc/articles/PMC139616</a> <a href="#fnref:8" class="footnote-back-ref">↩</a></p></li> <li id="fn:9"><p>Pearson, J.P.; Van Deiden, C.; Iglewski, B.H. (1999). "Active efflux and diffusion are involved in transport of Pseudomonas aeruginosa cell-to-cell signals". J. Bacteriol. 181 (4): 1203–1210. doi:10.1128/JB.181.4.1203-1210.1999. PMC 93498. PMID 9973347. <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC93498" target="_blank">https://www.ncbi.nlm.nih.gov/pmc/articles/PMC93498</a> <a href="#fnref:9" class="footnote-back-ref">↩</a></p></li> <li id="fn:10"><p>Fuqua, C.; Winans, S.C. (1996). "Conserved cis-acting promoter elements are required for density-dependent transcription of Agrobacterium tumefaciens conjugal transfer genes". J. Bacteriol. 178 (2): 434–440. doi:10.1128/jb.178.2.435-440.1996. PMC 177675. PMID 8550463. <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC177675" target="_blank">https://www.ncbi.nlm.nih.gov/pmc/articles/PMC177675</a> <a href="#fnref:10" class="footnote-back-ref">↩</a></p></li> <li id="fn:11"><p>Freeman, J.A.; Lilley, B.N.; Bassler, B.L. (2000). "A genetic analysis of the functions of LuxN: a two-component hybrid sensor kinase that regulates quorum sensing in Vibrio harveyi". Mol. Microbiol. 35 (1): 139–149. doi:10.1046/j.1365-2958.2000.01684.x. PMID 10632884. <a href="https://doi.org/10.1046%2Fj.1365-2958.2000.01684.x" target="_blank">https://doi.org/10.1046%2Fj.1365-2958.2000.01684.x</a> <a href="#fnref:11" class="footnote-back-ref">↩</a></p></li> <li id="fn:12"><p>Dunny, G.M.; Leonard, B.A. (1997). "Cell-cell communication in gram-positive bacteria". Annu. Rev. Microbiol. 51: 527–564. doi:10.1146/annurev.micro.51.1.527. PMID 9343359. <a href="/wiki/Doi_(identifier)" target="_blank">/wiki/Doi_(identifier)</a> <a href="#fnref:12" class="footnote-back-ref">↩</a></p></li> <li id="fn:13"><p>Harvastein, L.S.; Diep, D.B.; Nes, I.F. (1995). "A family of ABC transporters carry out proteolytic processing of their substrates concomitant with export". Mol. Microbiol. 16 (2): 229–240. doi:10.1111/j.1365-2958.1995.tb02295.x. PMID 7565085. S2CID 8086601. <a href="/wiki/Doi_(identifier)" target="_blank">/wiki/Doi_(identifier)</a> <a href="#fnref:13" class="footnote-back-ref">↩</a></p></li> <li id="fn:14"><p>Miller, M.B.; Bassler, B.L. (2001). "Quorum Sensing in Bacteria". Annu. Rev. Microbiol. 55: 165–199. doi:10.1146/annurev.micro.55.1.165. PMID 11544353. <a href="/wiki/Doi_(identifier)" target="_blank">/wiki/Doi_(identifier)</a> <a href="#fnref:14" class="footnote-back-ref">↩</a></p></li> <li id="fn:15"><p>Cao, J.; Meighen, E.A. (1989). "Purification and structural identification of an autoinducer for the luminescence system of Vibrio harveyi". J. Biol. Chem. 264 (36): 21670–21676. doi:10.1016/S0021-9258(20)88238-6. PMID 2600086. <a href="https://doi.org/10.1016%2FS0021-9258%2820%2988238-6" target="_blank">https://doi.org/10.1016%2FS0021-9258%2820%2988238-6</a> <a href="#fnref:15" class="footnote-back-ref">↩</a></p></li> <li id="fn:16"><p>Miller, M.B.; Bassler, B.L. (2001). "Quorum Sensing in Bacteria". Annu. Rev. Microbiol. 55: 165–199. doi:10.1146/annurev.micro.55.1.165. PMID 11544353. <a href="/wiki/Doi_(identifier)" target="_blank">/wiki/Doi_(identifier)</a> <a href="#fnref:16" class="footnote-back-ref">↩</a></p></li> <li id="fn:17"><p>Miller, M.B.; Bassler, B.L. (2001). "Quorum Sensing in Bacteria". Annu. Rev. Microbiol. 55: 165–199. doi:10.1146/annurev.micro.55.1.165. PMID 11544353. <a href="/wiki/Doi_(identifier)" target="_blank">/wiki/Doi_(identifier)</a> <a href="#fnref:17" class="footnote-back-ref">↩</a></p></li> <li id="fn:18"><p>Engebrecht, J.; Nealson, K.; Silverman, M. (1983). "Bacterial bioluminescence: isolation and genetic analysis of functions from Vibrio fischeri". Cell. 32 (3): 773–781. doi:10.1016/0092-8674(83)90063-6. PMID 6831560. S2CID 10882547. <a href="/wiki/Doi_(identifier)" target="_blank">/wiki/Doi_(identifier)</a> <a href="#fnref:18" class="footnote-back-ref">↩</a></p></li> <li id="fn:19"><p>Engebrecht, J.; Silverman, M. (1984). "Identification of genes and gene products necessary for bacterial bioluminescence". Proc. Natl. Acad. Sci. USA. 81 (13): 4154–4158. doi:10.1073/pnas.81.13.4154. PMC 345387. PMID 6377310. <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC345387" target="_blank">https://www.ncbi.nlm.nih.gov/pmc/articles/PMC345387</a> <a href="#fnref:19" class="footnote-back-ref">↩</a></p></li> <li id="fn:20"><p>Miller, M.B.; Bassler, B.L. (2001). "Quorum Sensing in Bacteria". Annu. Rev. Microbiol. 55: 165–199. doi:10.1146/annurev.micro.55.1.165. PMID 11544353. <a href="/wiki/Doi_(identifier)" target="_blank">/wiki/Doi_(identifier)</a> <a href="#fnref:20" class="footnote-back-ref">↩</a></p></li> <li id="fn:21"><p>McFall-Ngai, M.J.; Ruby, E. G. (1991). "Symbiont recognition and subsequent morphogenesis as early events in an animal– bacterial mutualism". Science. 254 (5037): 1491–1494. doi:10.1126/science.1962208. PMID 1962208. <a href="/wiki/Doi_(identifier)" target="_blank">/wiki/Doi_(identifier)</a> <a href="#fnref:21" class="footnote-back-ref">↩</a></p></li> <li id="fn:22"><p>Young, R.E.; Roper, C.F. (1976). "Bioluminscent countershading in midwater animals: evidence from living squid". Science. 191 (4231): 1046–1048. doi:10.1126/science.1251214. PMID 1251214. <a href="/wiki/Doi_(identifier)" target="_blank">/wiki/Doi_(identifier)</a> <a href="#fnref:22" class="footnote-back-ref">↩</a></p></li> <li id="fn:23"><p>Eberhard, A.; Burlingame, A.L.; Eberhard, C.; Kenyon, G.L.; Nealson K.H.; Oppenheimer, N.J. (1981). "Structural identification of autoinducer of Photobacterium fischeri luciferase". Biochemistry. 20 (9): 2444–2449. doi:10.1021/bi00512a013. PMID 7236614. <a href="/wiki/Doi_(identifier)" target="_blank">/wiki/Doi_(identifier)</a> <a href="#fnref:23" class="footnote-back-ref">↩</a></p></li> <li id="fn:24"><p>Engebrecht, J.; Silverman, M. (1984). "Identification of genes and gene products necessary for bacterial bioluminescence". Proc. Natl. Acad. Sci. USA. 81 (13): 4154–4158. doi:10.1073/pnas.81.13.4154. PMC 345387. PMID 6377310. <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC345387" target="_blank">https://www.ncbi.nlm.nih.gov/pmc/articles/PMC345387</a> <a href="#fnref:24" class="footnote-back-ref">↩</a></p></li> <li id="fn:25"><p>Kaplan, H.B.; Greenberg, E.P. (1985). "Diffusion of autoinducer is involved in regulation of the Vibrio fischeri luminescence system". J. Bacteriol. 163 (3): 1210–1214. doi:10.1128/jb.163.3.1210-1214.1985. PMC 219261. PMID 3897188. <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC219261" target="_blank">https://www.ncbi.nlm.nih.gov/pmc/articles/PMC219261</a> <a href="#fnref:25" class="footnote-back-ref">↩</a></p></li> <li id="fn:26"><p>Eberhard, A.; Burlingame, A.L.; Eberhard, C.; Kenyon, G.L.; Nealson K.H.; Oppenheimer, N.J. (1981). "Structural identification of autoinducer of Photobacterium fischeri luciferase". Biochemistry. 20 (9): 2444–2449. doi:10.1021/bi00512a013. PMID 7236614. <a href="/wiki/Doi_(identifier)" target="_blank">/wiki/Doi_(identifier)</a> <a href="#fnref:26" class="footnote-back-ref">↩</a></p></li> <li id="fn:27"><p>Choi, S.H.; Greenberg, E.P. (1991). "The C-terminal region of the Vibrio fischeri LuxR protein contains an inducer-independent lux gene activating domain". Proc. Natl. Acad. Sci. USA. 88 (24): 11115–11119. doi:10.1073/pnas.88.24.11115. PMC 53084. PMID 1763027. <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC53084" target="_blank">https://www.ncbi.nlm.nih.gov/pmc/articles/PMC53084</a> <a href="#fnref:27" class="footnote-back-ref">↩</a></p></li> <li id="fn:28"><p>Engebrecht, J.; Silverman, M. (1984). "Identification of genes and gene products necessary for bacterial bioluminescence". Proc. Natl. Acad. Sci. USA. 81 (13): 4154–4158. doi:10.1073/pnas.81.13.4154. PMC 345387. PMID 6377310. <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC345387" target="_blank">https://www.ncbi.nlm.nih.gov/pmc/articles/PMC345387</a> <a href="#fnref:28" class="footnote-back-ref">↩</a></p></li> <li id="fn:29"><p>Singh, P.K.; Schaefer, A.L.; Parsek, M.R.; Moninger, T.O.; Welsh, M.J.; Greenberg E.P. (2000). "Quorum-sensing signals indicate that cystic fibrosis lungs are infected with bacterial biofilms". Nature. 407 (6805): 762–764. doi:10.1038/35037627. PMID 11048725. S2CID 4372096. <a href="/wiki/Doi_(identifier)" target="_blank">/wiki/Doi_(identifier)</a> <a href="#fnref:29" class="footnote-back-ref">↩</a></p></li> <li id="fn:30"><p>Passador, L.; Cook, J.M.; Gambello, M.J.; Rust, L.; Iglewski, B.H (1993). "Expression of Pseudomonas aeruginosa virulence genes requires cell-cell communication". Science. 260 (5111): 1127–1130. doi:10.1126/science.8493556. PMID 8493556. <a href="/wiki/Doi_(identifier)" target="_blank">/wiki/Doi_(identifier)</a> <a href="#fnref:30" class="footnote-back-ref">↩</a></p></li> <li id="fn:31"><p>Brint, J.M.; Ohman, D.E. (1995). "Synthesis of multiple exoproducts in Pseudomonas aeruginosa is under the control of RhlR-RhlI, another set of regulators in strain PAO1 with homology to the autoinducer responsive LuxR-LuxI family". J. Bacteriol. 177 (24): 7155–7163. doi:10.1128/jb.177.24.7155-7163.1995. PMC 177595. PMID 8522523. <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC177595" target="_blank">https://www.ncbi.nlm.nih.gov/pmc/articles/PMC177595</a> <a href="#fnref:31" class="footnote-back-ref">↩</a></p></li> <li id="fn:32"><p>Pearson, J.P.; Gray, K.M.; Passador, L.; Tucker, K.D.; Eberhard, A.; et al. (1994). "Structure of the autoinducer required for expression of Pseudomonas aeruginosa virulence genes". Proc. Natl. Acad. Sci. USA. 91 (1): 197–201. doi:10.1073/pnas.91.1.197. PMC 42913. PMID 8278364. <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC42913" target="_blank">https://www.ncbi.nlm.nih.gov/pmc/articles/PMC42913</a> <a href="#fnref:32" class="footnote-back-ref">↩</a></p></li> <li id="fn:33"><p>Pearson, J.P.; Passador, L.; Iglewski, B.H.; Greenberg, E.P. (1995). "A second N-acylhomoserine lactone signal produced by Pseudomonas aeruginosa". Proc. Natl. Acad. Sci. USA. 92 (5): 1490–1494. doi:10.1073/pnas.92.5.1490. PMC 42545. PMID 7878006. <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC42545" target="_blank">https://www.ncbi.nlm.nih.gov/pmc/articles/PMC42545</a> <a href="#fnref:33" class="footnote-back-ref">↩</a></p></li> <li id="fn:34"><p>Passador, L.; Cook, J.M.; Gambello, M.J.; Rust, L.; Iglewski, B.H (1993). "Expression of Pseudomonas aeruginosa virulence genes requires cell-cell communication". Science. 260 (5111): 1127–1130. doi:10.1126/science.8493556. PMID 8493556. <a href="/wiki/Doi_(identifier)" target="_blank">/wiki/Doi_(identifier)</a> <a href="#fnref:34" class="footnote-back-ref">↩</a></p></li> <li id="fn:35"><p>Ochsner, U.A.; Reiser, J. (1995). "Autoinducer-mediated regulation of rhamnolipid biosurfactant synthesis in Pseudomonas aeruginosa". Proc. Natl. Acad. Sci. USA. 92 (14): 6424–6428. doi:10.1073/pnas.92.14.6424. PMC 41530. PMID 7604006. <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC41530" target="_blank">https://www.ncbi.nlm.nih.gov/pmc/articles/PMC41530</a> <a href="#fnref:35" class="footnote-back-ref">↩</a></p></li> <li id="fn:36"><p>Brint, J.M.; Ohman, D.E. (1995). "Synthesis of multiple exoproducts in Pseudomonas aeruginosa is under the control of RhlR-RhlI, another set of regulators in strain PAO1 with homology to the autoinducer responsive LuxR-LuxI family". J. Bacteriol. 177 (24): 7155–7163. doi:10.1128/jb.177.24.7155-7163.1995. PMC 177595. PMID 8522523. <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC177595" target="_blank">https://www.ncbi.nlm.nih.gov/pmc/articles/PMC177595</a> <a href="#fnref:36" class="footnote-back-ref">↩</a></p></li> <li id="fn:37"><p>Pesci, E.C.; Pearson, J.P.; Seed, P.C.; Iglewski, B.H. (1997). "Regulation of las and rhl quorum sensing in Pseudomonas aeruginosa". J. Bacteriol. 179 (10): 3127–3132. doi:10.1128/jb.179.10.3127-3132.1997. PMC 179088. PMID 9150205. <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC179088" target="_blank">https://www.ncbi.nlm.nih.gov/pmc/articles/PMC179088</a> <a href="#fnref:37" class="footnote-back-ref">↩</a></p></li> <li id="fn:38"><p>Miller, M.B.; Bassler, B.L. (2001). "Quorum Sensing in Bacteria". Annu. Rev. Microbiol. 55: 165–199. doi:10.1146/annurev.micro.55.1.165. PMID 11544353. <a href="/wiki/Doi_(identifier)" target="_blank">/wiki/Doi_(identifier)</a> <a href="#fnref:38" class="footnote-back-ref">↩</a></p></li> <li id="fn:39"><p>Pesci, E.C.; Milbank, J.B.; Pearson, J.P.; McKnight, S.; Kende, A.S.; et al. (1999). "). Quinolone signaling in the cell-to-cell communication system of Pseudomonas aeruginosa" (PDF). Proc. Natl. Acad. Sci. USA. 96 (20): 11229–11234. doi:10.1073/pnas.96.20.11229. PMC 18016. PMID 10500159. <a href="http://thescholarship.ecu.edu/bitstream/10342/3071/1/Quinolone%20signaling.pdf" target="_blank">http://thescholarship.ecu.edu/bitstream/10342/3071/1/Quinolone%20signaling.pdf</a> <a href="#fnref:39" class="footnote-back-ref">↩</a></p></li> <li id="fn:40"><p>Piper, K.R.; Beck von Bodman, S.; Farrand, S.K. (1993). "Conjugation factor of Agrobacterium tumefaciens regulates Ti plasmid transfer by autoinduction". Nature. 362 (6419): 448–450. doi:10.1038/362448a0. PMID 8464476. S2CID 4373143. <a href="/wiki/Doi_(identifier)" target="_blank">/wiki/Doi_(identifier)</a> <a href="#fnref:40" class="footnote-back-ref">↩</a></p></li> <li id="fn:41"><p>Zhang, L.; Murphy, P.J.; Kerr, A.; Tate, M.E. (1993). "Agrobacterium conjugation and gene regulation by N-acyl-L-homoserine lactones". Nature. 362 (6419): 445–448. doi:10.1038/362446a0. PMID 8464475. S2CID 4370414. <a href="/wiki/Doi_(identifier)" target="_blank">/wiki/Doi_(identifier)</a> <a href="#fnref:41" class="footnote-back-ref">↩</a></p></li> <li id="fn:42"><p>Hinton, J.C.; Sidebotham, J.M.; Hyman, L.J.; Perombelon, M.C.; Salmond, G.P. (1989). "). Isolation and characterisation of transposon-induced mutants of Erwinia carotovora subsp. atroseptica exhibiting reduced virulence". Mol. Gen. Genet. 217 (1): 141–148. doi:10.1007/bf00330953. PMID 2549365. S2CID 27047539. <a href="/wiki/Doi_(identifier)" target="_blank">/wiki/Doi_(identifier)</a> <a href="#fnref:42" class="footnote-back-ref">↩</a></p></li> <li id="fn:43"><p>Bainton, N.J.; Stead, P.; Chhabra, S.R.; Bycroft, B.W.; Salmond, G.P.; et al. (1992). "N-(3-oxohexanoyl)-L-homoserine lactone regulates carbapenem antibiotic production in Erwinia carotovora". Biochem. J. 288 (3): 997–1004. doi:10.1042/bj2880997. PMC 1131986. PMID 1335238. <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1131986" target="_blank">https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1131986</a> <a href="#fnref:43" class="footnote-back-ref">↩</a></p></li> <li id="fn:44"><p>Miller, M.B.; Bassler, B.L. (2001). "Quorum Sensing in Bacteria". Annu. Rev. Microbiol. 55: 165–199. doi:10.1146/annurev.micro.55.1.165. PMID 11544353. <a href="/wiki/Doi_(identifier)" target="_blank">/wiki/Doi_(identifier)</a> <a href="#fnref:44" class="footnote-back-ref">↩</a></p></li> <li id="fn:45"><p>Dawson, M.; Sia, R. (1931). "In vitro transformation of pneumococcal types I. A technique for inducing transformation of pneumococcal types in vitro". J. Exp. Med. 54 (5): 681–699. doi:10.1084/jem.54.5.681. PMC 2132061. PMID 19869950. <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2132061" target="_blank">https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2132061</a> <a href="#fnref:45" class="footnote-back-ref">↩</a></p></li> <li id="fn:46"><p>Havarstein, L.S.; Morrison, D.A. (1999). "Quorum sensing and peptide pheromones in Streptococcal competence for genetic transformation". Cell-Cell Signaling in Bacteria. (Washington, DC: ASM Press): 9–26. <a href="#fnref:46" class="footnote-back-ref">↩</a></p></li> <li id="fn:47"><p>Havarstein, L.S.; Coomaraswamy, G.; Morrison, D.A. (1995). "An unmodified heptadecapeptide pheromone induces competence for genetic transformation in Streptococcus pneumoniae". Proc. Natl. Acad. Sci. USA. 92 (24): 11140–11144. doi:10.1073/pnas.92.24.11140. PMC 40587. PMID 7479953. <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC40587" target="_blank">https://www.ncbi.nlm.nih.gov/pmc/articles/PMC40587</a> <a href="#fnref:47" class="footnote-back-ref">↩</a></p></li> <li id="fn:48"><p>Pozzi, G.; Masala, L.; Iannelli, F.; Manganelli, R.; Havarstein, L.S.; et al. (1996). "Competence for genetic transformation in encapsulated strains of Streptococcus pneumoniae: two allelic variants of the peptide pheromone". J. Bacteriol. 178 (20): 6087–6090. doi:10.1128/jb.178.20.6087-6090.1996. PMC 178474. PMID 8830714. <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC178474" target="_blank">https://www.ncbi.nlm.nih.gov/pmc/articles/PMC178474</a> <a href="#fnref:48" class="footnote-back-ref">↩</a></p></li> <li id="fn:49"><p>Hui, F.M.; Morrison, D.A. (1991). "Genetic transformation in Streptococcus pneumoniae: nucleotide sequence analysis shows comA, a gene required for competence induction, to be a member of the bacterial ATP-dependent transport protein family". J. Bacteriol. 173 (1): 372–381. doi:10.1128/jb.173.1.372-381.1991. PMC 207196. PMID 1987129. <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC207196" target="_blank">https://www.ncbi.nlm.nih.gov/pmc/articles/PMC207196</a> <a href="#fnref:49" class="footnote-back-ref">↩</a></p></li> <li id="fn:50"><p>Pestova, E.V.; Havarstein, L.S.; Morrison, D.A. (1996). "Regulation of competence for genetic transformation in Streptococcus pneumoniae by an auto-induced peptide pheromone and a two-component regulatory system". Mol. Microbiol. 21 (4): 853–862. doi:10.1046/j.1365-2958.1996.501417.x. PMID 8878046. S2CID 487722. <a href="/wiki/Doi_(identifier)" target="_blank">/wiki/Doi_(identifier)</a> <a href="#fnref:50" class="footnote-back-ref">↩</a></p></li> <li id="fn:51"><p>Lee, M.S.; Morrison, D.A. (1999). "Identification of a new regulator of Streptococcus pneumoniae linking quorum sensing to competence for genetic transformation". J. Bacteriol. 181 (16): 5004–5016. doi:10.1128/JB.181.16.5004-5016.1999. PMC 93990. PMID 10438773. <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC93990" target="_blank">https://www.ncbi.nlm.nih.gov/pmc/articles/PMC93990</a> <a href="#fnref:51" class="footnote-back-ref">↩</a></p></li> <li id="fn:52"><p>Grossman, A.D. (1995). "Genetic networks controlling the initiation of sporulation and the development of genetic competence in Bacillis subtilis". Annu. Rev. Genet. 29: 477–508. doi:10.1146/annurev.ge.29.120195.002401. PMID 8825484. <a href="/wiki/Doi_(identifier)" target="_blank">/wiki/Doi_(identifier)</a> <a href="#fnref:52" class="footnote-back-ref">↩</a></p></li> <li id="fn:53"><p>Magnuson, R.; Solomon, J.; Grossman, A.D. (1994). "Biochemical and genetic characterization of a competence pheromone from B. subtilis". Cell. 77 (2): 207–216. doi:10.1016/0092-8674(94)90313-1. PMID 8168130. S2CID 20800369. <a href="/wiki/Doi_(identifier)" target="_blank">/wiki/Doi_(identifier)</a> <a href="#fnref:53" class="footnote-back-ref">↩</a></p></li> <li id="fn:54"><p>Solomon, J.M.; Magnuson, R.; Srivastava, A.; Grossman, A.D. (1995). "Convergent sensing pathways mediate response to two extracellular competence factors in Bacillus subtilis". Genes Dev. 9 (5): 547–558. doi:10.1101/gad.9.5.547. PMID 7698645. <a href="https://doi.org/10.1101%2Fgad.9.5.547" target="_blank">https://doi.org/10.1101%2Fgad.9.5.547</a> <a href="#fnref:54" class="footnote-back-ref">↩</a></p></li> <li id="fn:55"><p>Turgay, K.; Hahn, J.; Burghoorn, J.; Dubnau, D. (1998). "Competence in Bacillus subtilis is controlled by regulated proteolysis of a transcription factor". EMBO J. 17 (22): 6730–6738. doi:10.1093/emboj/17.22.6730. PMC 1171018. PMID 9890793. <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1171018" target="_blank">https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1171018</a> <a href="#fnref:55" class="footnote-back-ref">↩</a></p></li> <li id="fn:56"><p>Hoch, J.A. (1995). "Control of cellular development in sporulating bacteria by the phosphorelay two-component signal transduction system.". Two Component Signal Transduction. Washington, DC.: ASM Press. pp. 129–144. doi:10.1128/9781555818319.ch8. ISBN 9781555818319. <a href="9781555818319" target="_blank">9781555818319</a> <a href="#fnref:56" class="footnote-back-ref">↩</a></p></li> <li id="fn:57"><p>Solomon, J.M.; Lazazzera, B.A.; Grossman, A.D. (1996). "Purification and characterization of an extracellular peptide factor that affects two different developmental pathways in Bacillus subtilis". Genes Dev. 10 (16): 2014–2024. doi:10.1101/gad.10.16.2014. PMID 8769645. <a href="https://doi.org/10.1101%2Fgad.10.16.2014" target="_blank">https://doi.org/10.1101%2Fgad.10.16.2014</a> <a href="#fnref:57" class="footnote-back-ref">↩</a></p></li> <li id="fn:58"><p>Lazazzera, B.A.; Solomon, J.M.; Grossman, A.D. (1997). "An exported peptide functions intracellularly to contribute to cell density signaling in B. subtilis". Cell. 89 (6): 917–925. doi:10.1016/S0092-8674(00)80277-9. hdl:1721.1/83874. PMID 9200610. S2CID 14321882. <a href="/wiki/Doi_(identifier)" target="_blank">/wiki/Doi_(identifier)</a> <a href="#fnref:58" class="footnote-back-ref">↩</a></p></li> <li id="fn:59"><p>Grossman, A.D. (1995). "Genetic networks controlling the initiation of sporulation and the development of genetic competence in Bacillis subtilis". Annu. Rev. Genet. 29: 477–508. doi:10.1146/annurev.ge.29.120195.002401. PMID 8825484. <a href="/wiki/Doi_(identifier)" target="_blank">/wiki/Doi_(identifier)</a> <a href="#fnref:59" class="footnote-back-ref">↩</a></p></li> </ol>